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Therapy and prevention of hepatocellular carcinoma using herbal drugs

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August 31, 2010 at 7:56 am

Cancer is a condition characterised by the uncontrolled growth and spread of abnormal cells, causing their massive aggregation producing either tumours or dispersal in the vascular system such as blood and lymph. Owing to a deviation from normal genetic makeup, cancer cells acquire immortality and a capability to evade apoptosis, non-responsiveness to anti-growth signals, self-sufficiency in growth factors, the ability to metastasise and to form new blood vessels that can supply nutrition and oxygen to the growing tissues. The transformation of normal to cancer cell occurs through accumulation of a series of genetic alterations or mutations, especially of oncogenes.

Carcinogenesis

There are many aetiological factors leading to cancer through a multistep process called carcinogenesis, which involves initiation, promotion, progression and malignant conversion. Mutation in a single cell initiates clonal expansion to form a premalignant lesion. These initiated cells will have resistance to cytotoxicity, defects in maturation, escape from senescence and have altered dependence on growth factors and hormones. Tumour promotion involves activation of cell surface receptors, activation/inhibition of cytosolic enzymes and nuclear transcription factors, stimulation of proliferation and inhibition of apoptotic cell death. Progression is accelerated by additional exposure to genotoxic agents and it is due to genetic instability and nonrandom sequential chromosomal aberrations. Malignant conversion involves multifocal change in premalignant lesions. There will be up-regulation of transcriptional activity and expression of modified cell surface molecules, gene amplification, alterations in cell-cycle regulatory genes, secreted proteases and methylation of DNA. All these changes facilitate migration and invasion.

Inhibition of carcinogenesis

As the progression of carcinogenesis is through a multistep pathway, there are many possible intervention sites inhibiting this progression. The procarcinogen can be detoxified and eliminated from the system. The conversion of procarcinogen to ultimate carcinogen is through multiple mechanisms including metabolic activation by enzymes. These mechanisms can be inhibited by blocking those enzymes involved in the activation step and several natural compounds of plant origin are reported as blocking agents in the chemoprevention of cancer, including flavonoids, ellagic acid and sulforaphane. These either block the conversion of carcinogen to ultimate carcinogen, or prevent the action of active metabolites on the normal cell. They may also alter carcinogen metabolism, enhance carcinogen detoxification, scavenge electrophiles and reactive oxygen species or enhance DNA repair.

The conversion of normal cells from preneoplastic cells to neoplastic cells takes several years, either by a second exposure to the carcinogen or promoting agent and accumulation of genetic variations. These steps can be inhibited by compounds such as curcumin, resveratrol, carotenoids, retinoids and genistein, which inhibit the malignant transformation of initiated cells by scavenging reactive oxygen species, altering gene expression, decreasing inflammation, suppressing proliferation, inducing differentiation, encouraging apoptosis, enhancing immunity or inhibiting angiogenesis and metastasis. Several chemopreventive phytochemicals have been shown to interfere with the cell-cycle regulatory pathways, qualifying them as potential therapeutic agents. Some are powerful inhibitors of growth factor receptors, including epidermal growth factor receptor (EGFR), and a variety of flavonoids are inhibitory, e.g. apigenin, luteolin, quercetin, catechin, epigallocatechin gallate, hesperitin, anthocyanins, genistein, with potential use in preventive anticancer treatment. Some phytochemicals undergoing clinical trials in the inhibition of carcinogenesis are given in Table: Selected ongoing Phase 1 and II cancer prevention trials sponsored by the US National Cancer Institute.

Table: Selected ongoing Phase 1 and II cancer prevention trials sponsored by the US National Cancer Institute
Target organ Agent
Phase 1 trials
Breast Soy isoflavones
Colon Curcumin
Prostate Lycopene (3 trials); Soy isoflavones
Skin Epigallocatechin gallate
Phase II trials
Anogenital warts, human papillomavirus, HIV Indole-3-carbinol
Cervix 9-cis-Retinoic acid
Prostate Soy (dietary); soy isoflavones

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignant tumour of the liver and is the fifth most common cancer in the world, ranking fourth in annual mortality rates. An estimated 564 000 new cases of HCC are diagnosed each year, with the highest incidence in eastern and southeastern Asia, some of the western Pacific islands and sub-Saharan Africa. Men are affected four to eight times more often than women and the incidence generally increases with increasing age, although there is a definite shift towards a younger age distribution in black African and ethnic Chinese populations.

Aetiological factors

There are some well-documented aetiological associations of HCC. The aetiological association between hepatitis-B virus (HBV) and HCC is well established. Chronic HBV infection is the leading risk factor and it has been estimated that 53% of cases worldwide are related to HBV. Malignant transformation occurs after a long period of chronic liver disease, frequently associated with cirrhosis. Chronic inflammation of the liver, continuous cell death and consequent cell proliferation might increase the occurrence of genetic alterations and risk of cancer. The long-term expression of regulator gene product of the X-gene and large envelope proteins (LHBs) are thought to play a major role in tumorigenesis. This viral oncoprotein behaves as a transcriptional transactivator, which activates oncogenes, cytokines and growth factors. A direct role of the virus through integration of viral DNA directly to host genome has also been hypothesised that may enhance chromosomal instability, large inverted duplications, deletions, amplifications or chromosomal translocations which lead to the activation of oncogenic pathways.

Chronic HCV (hepatitis C virus) infection is also associated with HCC. The HCC incidence rate in patients with HCV-related cirrhosis is about 3.7%.

Chemical carcinogens which are linked to HCC include nitrites, hydrocarbons, solvents, organochlorine pesticides, primary metals and polychlorinated biphenyls. Of all the chemicals linked to HCC, ethanol is the most important one that leads to HCC. Overconsumption of alcohol is one of the leading causes of liver cirrhosis which makes the patient more susceptible to HBV and HCV infection.

Aflatoxins produced by the fungi, Aspergillus flavus and A. parasiticus have also been linked to HCC. These fungal species grow on grains, peanuts and other food products and are the most common cause of food spoilage. These fungi also produce aflatoxins, aflatoxin Bl being the most hepatotoxic and chronic exposure to these mycotoxins will lead to HCC.

Some congenital conditions also lead to development of HCC. Genetic diseases such as haemochromatosis, Wilson’s disease, hereditary tyrosinaemia, type I glycogen storage disease and porphyria, have all been linked to a high incidence of HCC.

Symptoms and markers

The symptoms related to the early stages of HCC are poor. When HCC presents with clinical symptoms, the tumour is usually advanced and there are few therapeutic options. The current effective treatments available are only applicable in a relatively small proportion of early stage cases.

Serum a-fetoprotein is a useful tumour marker for the detection and monitoring of HCC development, but gives false-negatives in about 40% of patients. Serum Ύ-glutamyl transpeptidase (GGT) is frequently overexpressed in cancer cells. GGT activity is a sensitive marker of hepatobiliary disorders, exhibiting tissue-specific expressions under various physiological and pathological conditions. Other enzymes that are increased in the blood during HCC include alkaline phosphatase, alanine trans-aminase and aspartate transaminase, but they are non-specific.

The overexpression of transforming growth factor (TGF)-β1 and TGF-β1 messenger RNA is seen in most patients with HCC. The level of insulinlike growth factor (IGF)-II and IGF-II mRNA is also overexpressed in HCC. The analysis of telomerase activity in combination with α-fetoprotein increases the accuracy of HCC diagnosis to about 93%.

Even though tumours present limitations for cytogenetic analysis, there are some reports of cytogenetic analysis of HCC. They include chromosome 1p abnormalities and 8q amplification. Molecular studies have demonstrated frequent loss of heterozygosity on 1p, 4q, 8p, 11p, 13q, 16q and 17p and amplification of 8q areas in HCC.

Models

Rodents are usually studied as models of hepatic carcinogenesis. Many chemicals induce liver cancer in rodents since their livers are very sensitive to chemical carcinogens. Thus, a single experimental protocol can be used to understand the mechanisms of a number of carcinogens. The low cost of rodents and their potential for genetic studies and manipulation are also attributes. Apart from this, a fairly extensive understanding of liver biology has made rodent HCC a popular model. Other models used for HCC study include hamsters and other non-primates.

The chemicals used to study the initiation of HCC include nitrosamines, aromatic amines, vinyl chloride, polycyclic aromatic hydrocarbons, hetero-cyclic amines, aflatoxin and tamoxifen. The promoters which are used after initiation include phenobarbital, dioxin and polychlorinated biphenyl. The mechanism of action of these chemical carcinogens is combination with DNA to form adducts, either by direct binding to DNA, or after enzymatic activation in the liver to produce the carcinogen. Some agents that produce hepatic carcinogenesis are discussed below.

Polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons require metabolic activation to elicit their detrimental effect, e.g. benzo(a)pyrene is enzymatically activated to the 7,8-dihydrodiol, which induces both somatic mutations in crucial genes through DNA binding and subsequent outgrowth of irreversibly transformed cells.

Aryl amines/amides

In rodents these compounds induce tumours in the liver, e.g. acetamido-fluorine undergoes N-hydroxylation in liver cells. Additional tumour-promoting activities of acetamido-fluorine include the triggering of adaptive responses in mitochondria permeability transition pores and Bcl-2 production levels that increase resistance to apoptosis.

Alcohol

The mechanism of ethanol-induced cancer is closely related to its metabolism. Acetaldehyde, the end-product of ethanol metabolism, is the causative agent of cancer in chronic conditions. Oxidative stress and cirrhosis are important factors in ethanol-induced HCC.

Nitrosamines

These are the most widely used chemical carcinogen for animal experiments. N‘-nitrosodiethylamine (NDEA) is metabolised in the liver and its ethyl radical product is responsible for induction of HCC. This radical attacks the DNA and produces genetic changes which result in carcinogenesis. It also produces the conversion of certain proto-oncogenes to oncogenes.

Azo dyes

Para-dimethylaminoazobenzene (p-DAB) is metabolised to monoaminoazobenzene by N-demethylation and subsequently to aminoazobenzene or to N-hydroxy-N-methyl-4-aminoazobenzene. Covalent bindings of these metabolites with DNA are major carcinogenic factors.

Aflatoxins

Aflatoxins are highly mutagenic and are metabolised by cytochrome p450 to their epoxides, which results in formation of DNA adducts with the guanine N7, thus causing carcinogenicity.

Treatment

If detected early, suitable curative treatments include surgical resection, liver transplantation and percutaneous ablation. In patients with advanced stage of HCC, transarterial chemoembolisation has been proved to improve survival in selected candidates. Other therapeutic modalities such as intra-arterial chemotherapy and internal radiation offer promising results but have not been shown to improve survival. As HCC is usually chemoresistant, cytotoxic drugs are poorly tolerated in cirrhotic patients so many of the known anticancer agents, e.g. tamoxifen, octreotide, interferon, fail to produce any benefit in HCC patients. Promising results have been obtained with agents targeting receptor tyrosine kinase pathways. Since HCC is dependent on angiogenesis, molecules targeting the angiogenesis are currently under investigation. BAY 43-9006, which inhibits multiple pathways, mainly Raf kinase and VEGF, has been undergoing Phase II and III trials and has shown a partial response in a patient with advanced HCC.

The presence of unlimited chemical molecules, with diverse mechanisms, present in herbal drugs makes them interesting starting points in the search for newer drugs for cancer treatment.

Natural templates for treatment

The plant kingdom produces many potent pharmacologically active components, several of which have provided promising results to combat various diseases. Possible uses of herbal drugs in cancer are illustrated in Figure: Potential uses of herbal drugs in cancer treatment.

Figure: Potential uses of herbal drugs in cancer treatment.

Figure: Potential uses of herbal drugs in cancer treatment.

The chemical basis of some anticancer plants has been elucidated and some are now used clinically. Plant extracts and their constituents which show significant activity against hepatic cancer are described in more detail below.

Curcuma longa (turmeric)

The rhizome of C. longa (Zingiberaceae) is described as an anti-inflammatory agent in Ayurveda and is widely used in foods and as a medicine thoughout India and other Asian countries as a treatment for liver disorders, including cancer. The most-studied ingredient in the rhizome is curcumin but several related compounds are present such as demethoxy-curcumin and bidemethoxycurcumin.

Curcumin treatment has been reported to reduce tumour incidence and inhibit the liver inflammation and hyperplasia in N-nitrosodiethylamine-induced liver-cancer-bearing animals. The chemopreventive effect of turmeric and curcumin against diethylnitrosamine-induced and phenobarbital-promoted hepatocarcinogenesis has been reported. Curcumin also suppressed diethylnitrosamine-induced development of altered hepatic foci in rat liver. The number of Ύ-GT positive foci induced by aflatoxin Bl was found to be reduced by curcumin treatment. Curcumin significantly protected the liver from oxidative stress-induced damage during chemically induced hepatocarcinogenesis in rats.

In a patient study, Curcuma aromatic oil showed a positive effect in treating primary liver cancer with longer survival time and myelosuppression. Curcumin treatment reduced the tumour incidence by inhibiting angiogenesis through down-regulating cyclo-oxygenase 2 and vascular endothelial growth factor in HepG2 cells. It was reported that curcumin induces mitochondrial and nuclear DNA damage, thereby inducing apoptosis through caspase 3 and 9 activation. Curcumin also suppressed intrahepatic metastasis mediated by the inhibition of MMP-9 and through alteration of cytoskeletal organisation. In-vitro studies showed that the production of p21(ras) was inhibited by curcumin. It also inhibited transcription factor NF-kB and IAP gene expression. External curcumin application has been tried as a palliative therapy for cancerous skin lesions. Clinical trials (Phase I and II) of curcumin are being carried out in several hospitals to find out its therapeutic role against colon cancer, pancreatic cancer, hepatocellular cancinoma and multiple myeloma. Curcumin was found to be non-toxic at doses up to 12 g/day in patients.

Silybum marianum (milk thistle)

The active ingredients present in Silybum marianum (Compositae) are the flavonolignans silymarin and silybinin. Silymarin has been proposed as a promising chemotherapeutic adjuvant for the treatment of liver cancer. N‘-nitrosodiethylamine-induced hepatocellular carcinoma was found to be inhibited by silymarin by modulating antioxidant defence status in rats. Silybin was found to inhibit the growth of Hep3B and HepG2 cells by G1 arrest. The apoptosis-inducing property of silybin has been shown to be through decreasing cyclin D1, cyclin D3, cyclin E and cyclin dependent kinases 2 and 4. Silymarin can suppress the proliferation of a variety of tumour cells through cell cycle arrest at the G1/S-phase, induction of cyclin-dependent kinase inhibitors (such as p15, p21 and p27), down-regulation of anti-apoptotic gene products (e.g. Bcl-2 and Bcl-xL), inhibition of cell-survival kinases (AKT, PKC and MAPK) and inhibition of inflammatory transcription factors (e.g. NF-kβ). Silymarin can also down-regulate gene products involved in the proliferation of tumour cells (cyclin D1, EGFR, COX-2, TGF-beta, IGF-IR), invasion (MMP-9), angiogenesis (VEGF) and metastasis (adhesion molecules). The anti-inflammatory effects of silymarin are mediated through suppression of NF- kβ -regulated gene products, including COX-2, LOX, inducible iNOS, TNF and IL-1. Treatment of patients with hepatitis B or C infection with silymarin seemed to be effective, although no effect in decreasing viral load was found.

Camellia sinensis (tea)

Constituents of Camellia sinensis (Theaceae) include flavonols, e.g. myricetin, kaempferol and quercetin; as well as caffeine and proanthocyanidins such as epigallocatechin gallate. Green tea was observed to have protective effect on liver cancer in population-based studies.

In multidose NDEA-induced HCC followed by carbon tetrachloride injection and partial heptoectomy studies, it was found that treatment with tea polyphenols and pigment showed significant reduction in number and area of GST-positive foci, which is a proliferative indicator of precancerous liver lesions by immunohistochemistry.

Green tea was reported to exert antiproliferative activity towards hepatoma cells. Green tea was also reported to possess chemopreventive activity against nitrosamine-initiated hepatocellular carcinoma. It was found that the production of p21(WAF1/CIP1) was significantly induced and that of cyclin Dl and cyclin-dependent kinase 4 were inhibited in tea-treated animals. Tea catechins, black tea extract and oolong tea extract are also reported to inhibit hepatocellular carcinoma.

Allium sativum (garlic)

The bulbs of Allium sativum (Alliaceae) have been described as useful against inflammation and tumours in Ayurveda. The anticarcinogenic activity of whole garlic, as well as its isolated ingredients, against NDEA-induced hepatocellular carcinoma in animals is well documented. Aged garlic extract inhibited the development of putative lesions in rat hepatocarcino-genesis involving a slowing in the proliferation rate of liver cells after partial hepatoectomy. Garlic powder inhibited the formation of preneoplastic foci during hepatocarcinogenesis initiated by diethylnitrosamine through suppression of CYP2E1. The organosulphur compounds isolated from garlic are highly active against liver cancer. There was a decrease in the number of preneoplastic, GST-positive foci of the liver and also a down-regulation of IGF-I and iNOS mRNA expression in the liver of organosulphur-treated animals which were induced with 2-amino-3,8-dimethylimidazo [4-5-f] quinoxaline. The protective effect of diallylsulphide isolated from garlic against HCC was reported by Singh et al. (2004). S-allylcysteine, an organosulphur compound, showed inhibition of tumour incidence and lipid peroxidation in NDEA-induced hepatic cancer animals with simultaneous elevation in antioxidants.

Benzo(a)pyrene-induced cancer was found to be inhibited by garlic constituents such as diallylsulphide (DAS), diallyldisulphide (DADS) and diallyltrisulphide (DATS). Diallylsulphide prevented DNA adducts induced by the carcinogen, thereby preventing the initiation of oestrogen-induced cancer. Allylthiopyridazine derivatives induced apoptosis in Sk-Hep-1 cells through a caspase-3-dependent mechanism and this also contributes to their chemopreventive function. The antiproliferative property of aqueous garlic extract was studied in HepG2 cells and it was found that these compounds induced a p53/p21-dependent cell cycle arrest in G2/M phase and apoptosis through activation of c-Jun-NH (2) terminal kinase (JNK)/c-Jun phosphorylative cascade. DAS, DADS and DATS also caused G2/M phase arrest in human liver tumour cells.

Emblica officinalis Gaertn. (emblica)

The extract of fruits of Emblica officinalis (Euphorbiaceae) was reported to give chemoprotection against chemically induced carcinogenesis. The fruits are rich in polyphenolic compounds such as gallic acid, tannic acid, emblicanin A and B and ellagitannins. Polyphenolic compounds, such as epigallo-catechin gallate, found in tea are also present in Emblica officinalis. Because of the presence of these compounds, emblica extract has been shown to possess significant antioxidant activity and is also antimutagenic, inhibiting DNA adducts produced by benzo(a)pyrene. The polyphenolic fraction of Emblica officinalis was found to modulate NDEA-induced hepatic cancer in rats. In-vitro experiments showed that it inhibited DNA topoisomerase I in Saccharomyces cerevisiae mutant cell culture and also inhibited the activity of cdc25 tyrosine phosphatase.

Phyllanthus amarus

The fresh root of Phyllanthus amarus (Euphorbiaceae) is said to be an excellent remedy for jaundice. The components present in Phyllanthus amarus are lignans, e.g. phyllanthin; tannins, e.g. phyllanthusiin D3, amariin and amarulone; alkaloids, e.g. entnorsecurinine, diarylbutanes; and neolignans, e.g. phyllnirurin. A variety of hydrolysable tannins purified from Phyllanthus amarus were reported to be potent inhibitors of rat liver cyclic AMP-dependent protein kinase catalytic subunit. Phyllanthus amarus extract was reported to significantly inhibit NDEA-induced hepatocar-cinogenesis in rats in a dose-dependent manner. In another study the lifespan of rats bearing NDEA-induced hepatocellular carcinoma was found to be significantly increased by the treatment with Phyllanthus amarus, from 33 weeks to 52 weeks. Phyllanthus amarus extract has been shown to have antiviral activity against hepatitis B virus. In a patient study, it was found that approximately 60% of the carriers of HBV lost the virus within 1 month of Phyllanthus amarus treatment.

Picrorhiza kurroa (kutki)

The root/rhizomes of Picrorhiza kurroa (Scrophulariaceae) are used in Ayurveda against jaundice. The components present in the root include the glycosides picrorhizin and kutkin, and sterols. Picroliv, an iridoid glycoside mixture prepared from this plant, contains equal concentrations of picroside and kutkoside as well as vanillic acid and sterols. Amelioration of NDEA-induced hepatocellular carcinoma was seen in animals treated with Picrorhiza kurroa extract, and there was a significant reduction in the levels of drug-metabolising enzymes such as glutathione-S-transferase (GST) and aniline hydroxylase (AH). Liver morphology and histopathology also revealed the protective effect of the extract against chemical carcinogenesis. Picroliv was found to inhibit HCC and was also reported to possess protective effect against 1,2-dimethylhydrazine-induced HCC in animals. Picroliv significantly down-regulated transcription factor API and thereby decreased the level of c-fos mRNA as well as c-jun and c-fos proteins in liver tissue. This would indicate a base for their potential anti-HCC activity.

Semecarpus anacardium (marking nut)

The rind of the fruit of Semecarpus anacardium (Anacardiaceae) is used in Ayurvedic medicine against inflammatory diseases. The active ingredient is usually reckoned as anacardic acid. Semecarpus anacardium nut extract affords anti-cancer activity by enhancing both phase I and phase II enzymes and it has been proposed that the anticancer activity may be mediated through the induction of hepatic biotransformation enzymes. It was found to modulate the carcinogenic effect of aflatoxin by enhancing anti-oxidant capacity in the system.

Andrographis paniculata (creat)

The root of Andrographis paniculata (Acanthaceae) is used in both Ayurvedic and Chinese medicine. The component present is a diterpene lactone andrographolide. The roots also contain a variety of compounds including the sesquiterpene andrographolide. The effectiveness of Andrographis paniculata was found to be through modulating hepatic and extra-hepatic carcinogen-metabolising enzymes and antioxidant status. Andrographis paniculata extract and andrographolide stimulated CTL production through enhanced secretion of IL-2 and IFN-Ύ by T cells and thereby inhibited the tumour growth. The species has been reported to modulate the immune response through enhancing natural killer (NK) cell activity and antibody-dependent cell-mediated cytotoxicity and antibody-dependent complement mediated cytotoxicity in tumour-bearing animals.

Glycine max (soybean)

Glycine max (Papilionaceae) contains isoflavone glycosides genistein and diadzin as active principles but certain saponin constituents were also found to be biologically active. The administration of 30% soybean to the rat diet was found to have protective effect against hepatocarcinogenesis induced by DL-ethionone. There was a 92.7% increase in lifespan in rats with primary liver cancer when treated with doxorubicin encapsulated with soybean-derived sterylglycoside mixture when compared with free doxorubicin. Genistein was found to inhibit diethyl-nitrosamine-induced and phenobarbital-promoted HCC. Genistein has been reported to inhibit lung metastasis in animals. Genistein was found to inhibit cell proliferation and induced apoptosis through caspase-3 induction and caspase-2 activation. In another study apoptosis was induced by genistein in Hep 3B cells through initiating endoplasmic reticular stress relevant regulators including m-calpain, GADD 153, GRP 78 and caspase-12.

Panax ginseng (ginseng)

Panax ginseng (Araliaceae) root (white and red) is extensively used in traditional Chinese medicine against various diseases. Ginseng contains polysaccharides and saponins, those known as ginsenosides are commonly considered to be the active constituents. The incidence of liver tumour development was lower in animals treated with red ginseng extract, and the average number of tumours per mouse was significantly reduced in the treated group. White ginseng was also found to possess anticarcinogenic properties both in vitro and in vivo. In another study, red ginseng was found to possess both preventive as well as curative properties against diethylamine-induced hepatic cancers in rats.

Terminalia arjuna (arjuna bark)

Terminalia arjuna (Combretaceae) bark is extensively used against tumours in Ayurvedic medicine. Terminalia arjuna was reported to possess chemopreventive activity in NDEA-induced HCC-bearing animals. In another study, diethylnitrosamine-induced HCC was inhibited by Terminalia arjuna bark extract through modulating the antioxidant status in tumour-bearing animals. The ingredients of Terminalia arjuna bark include flavonoids, e.g. arjunone, arjunolone and luteolin; phenols, e.g. gallic acid and ellagic acid; and terpenoids, e.g. oleanolic acid. The antitumour potential of luteolin and triterpenoids has been reported, while phenolic ingredients have significant chemopreventive activity.

Other plants

Baubinia variegata and Baubinia racemosa were reported to ameliorate NDEA-induced HCC in rats through modulation of antioxidant enzymes. Chemopreventive potential of extracts from Tamarix gallica, Paullina cupana, Butea monosperma, Lygodium flexuosum, Indigofera aspalatboides, Apium graveolens, Solanum trilobatum, Ardisia compressa, Calotropis procera, Amaranthus gageticus, Astragalus membranaceus, Beta vulgaris, Cymbopogon citrates, Asteracantha longifolia, Triantbema portulacastrum etc. has been reported in hepatic cancer models in animals.

Conclusions

There is no really effective treatment for hepatocellular carcinoma and so it stands high in global cause of mortality. Chronic hepatitis and lifestyle-induced oxidative stress are the major factors associated with hepatic cancer. It is detected in the later stages in many patients, and the current treatment modalities fail to keep the disease under control. Plants and plant-derived compounds have been found to be effective against hepatic cancer in animal models and through a few clinical studies. The antiviral and free-radical scavenging activities of the plant-derived constituents in many cases have proven to be beneficial. Many of the compounds, e.g. curcumin, are in the process of being testing in clinical trials and are giving promising results, while explorations for newer compounds are still progressing.

Disorders of digestive system | Tags: , ,

Herbal medicines for functional gastrointestinal disorders

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August 28, 2010 at 7:38 am

Gastrointestinal complaints rank among the most frequent reasons why people seek medical advice. The most common functional gastrointestinal disorders (FGIDs) seen in clinical practice are functional dyspepsia (FD) and irritable bowel syndrome (IBS), characterised by recurrent episodes of gastrointestinal symptoms, in the absence of structural lesions that explain symptoms. While symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn are predominant in functional dyspepsia, abdominal discomfort, bloating and disturbed patterns of defecation (constipation, diarrhea or constipation/diarrhea) are common in patients with IBS. FGIDs reduce the health-related quality of life and account for an increased healthcare burden. The pathogenesis of functional gastrointestinal disorders is probably multi-factorial, genetic and environmental factors are thought to contribute to alterations in visceral sensory function, motility, bacterial overgrowth and central nervous system processing. Inflammation is considered a risk factor for the development of both functional dyspepsia and irritable bowel syndrome. Currently, the existing therapies to treat multiple symptoms of FGIDs are suboptimal, associated with restricted therapeutic potential and new agents are awaited that would improve global IBS symptoms. A wide variety of treatments have been used to manage functional gastrointestinal disorders and include Helicobacter pylori eradication, antacids, mucosal protectants, antisecretory agents, prokinetics, antidepressants and visceral analgesics. The fact that no single available therapy consistently provides relief to the majority of the patients validates the heterogeneity of these disorders. The emerging therapies are largely aimed to normalise pain perception and gastrointestinal motor and reflux function.

The therapy of functional gastrointestinal disorders is one of the domains of phytotherapeutic treatments. Traditionally, plants with a high tannin content, showing astringent properties, were particularly valued to treat diarrhea and dysentery whereas bitter, aromatic and bitter-aromatic plants were especially employed to treat gastrointestinal cramps and pain. Investigations on traditionally used plants have resulted in the isolation, and chemical and pharmacological characterisation of many different types of compounds. Most of these agents are helpful to prevent or arrest the progression, rather than to treat disease. Further, they exhibit pleotropic actions and therefore may serve as important leads for developing novel therapies for the treatment of functional gastrointestinal disorders.

So far, relatively few herbal medicines have been evaluated scientifically to prove their safety, potential benefits and effectiveness in gastrointestinal disorders (Table: Experimental studies on traditional herbs used in gastrointestinal disorders). This chapter specifically deals with the evaluation methods for the development of quality herbal medicines intended to be useful in FGIDs.

Functional dyspepsia

Functional dyspepsia is a clinical syndrome, whose origin is unknown, defined by chronic or recurrent pain or discomfort in the upper abdomen. On the basis of the Rome III diagnostic criteria for functional gastrointestinal disorders, patients who suffer from functional dyspepsia in the absence of any organic disease are categorised as having postprandial distress syndrome or epigastric pain syndrome for at least 3 months. About 15-30% of adult patients suffer from various different functional dyspeptic conditions. Several pathophysiological mechanisms are involved in functional dyspepsia, including visceral hypersensitivity, both in the stomach and the duodenum, impaired gastric accommodation, antral overdistention, delayed gastric emptying and abnormal duodenojejunal motility. Induction of gastric hypersensitivity by acid in the stomach seems to be important in a subset of patients. Many drugs can induce dyspepsia as a gastrointestinal side-effect, the major cause being the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for arthritis and chemotherapeutic agents in cancer. Studies also suggest a possible link with G-protein polymorphisms in dyspepsia.

Currently, functional dyspepsia is classified into ulcer-like dyspepsia, dysmotility-like dyspepsia and non-specific dyspepsia, in which symptoms do not clearly fit into any of the above categories. While antacids, H2-receptor antagonists and proton-pump inhibitors are useful in ulcer-like dyspepsia, pro-kinetic agents are more effective in dysmotility-like dyspepsia. Most therapies for patients with functional dyspepsia are intended to normalise pain perception and gastrointestinal motor and reflex function. Serotonin is the key mediator of gut function in relation to gastrointestinal motility, secretion and sensation of pain. There is limited evidence that the 5-hydroxytryptamine 5-HT3 antagonist alosetron has potential efficacy in functional dyspepsia, perhaps via visceral analgesic effects. Animal studies also suggest that acid can induce serotonin release from enterochromaffin cells in the duodenum, which may in turn activate 5-HT3 receptors and alter visceral sensation. Acid in the duodenum can also induce fundic relaxation. Thus, the interaction between acid and 5-HT3 receptor antagonism is of interest in functional dyspepsia. A number of compounds may have visceral analgesic effects in the upper gastrointestinal tract, including 5-HT3 antagonists and 5-HT4 agonists. Approximately 25% of patients with functional dyspepsia have slow gastric emptying, and perhaps 10% have accelerated gastric emptying. It is, therefore, important to avoid the use of prokinetic therapy in patients who have accelerated gastric emptying, as presumably this would worsen symptoms.

No standard therapy is currently available for functional dyspepsia. From ancient times, bitter herbal drugs have played a role in the therapy of patients with dyspeptic symptoms. Studies point out that different plant-derived extracts and their constituents can give gastro/cytoprotection through several mechanisms (Table: Experimental studies on traditional herbs used in gastrointestinal disorders). Flavonoids are highly gastroprotective probably due to enhancement of the release of nitric oxide and neuropeptides, such as calcitonin gene-related peptide, released from sensory afferent nerves, which increase gastric microcirculation. These appear to stimulate, at even very small concentrations, the secretion of the stomach as well as the digestive glands and strengthen the smooth musculature of the digestive tract. Bitter substances are often combined with essential oils, which act primarily as spasmolytics and analgesics and possess anti-Helicobacter pylori effects. They exert anti-inflammatory action by:

Table: Experimental studies on traditional herbs used in gastrointestinal disorders

Name Part used Use Constituents Study type Results
STW5 Iberogast® (herbal formula) Ethanolic extracts of 9 plants Functional dyspepsia (FD) and irritable bowel syndrome (IBS) Methionine-like sulphur-compounds Animal studies Diminished binding affinity of 5-HT(4), muscarinic M(3), and opioid receptors in vitro
Artichoke (Cynara scolymus L.) Leaf extract Irritable bowel syndrome (IBS) Caffeoylquinic acids and flavonoids Animal studies Protected animals from gastric ulceration
N-095 (crude drug containing red ginseng, polygala root, saffron, antelope horn and aloe wood) Dried powder Combat stress Multi components Experimental studies in rats Prevented gastric ulceration — induced by restraint and water-immersion stress
Baishouwu (Chinese herbal drug) Dried root tubers of 3 plants Gastric diseases Multicomponents Experimental studies in rats Offered gastroprotection against ethanol and indometacin-induced gastric lesions
Turmeric (Curcuma longa L.) Rhizome extract Ulcer and non-ulcer dyspepsia Curcumin (diferuloyl methane) Animal studies in vivo and anti-H. pylori in vitro Demonstrated antiulcer, anti-inflammatory, anticancer and analgesic effects
Peppermint (Mentha piperita L.) Leaf essential oil Gastroprotective use Menthol and menthonin Animal studies Antimicrobial, antispasmodic, antioxidant and analgesic effects
Anise (Pimpinella anisum L.) Seed aqueous suspension Gastroprotective use in Arab medicine Volatiles In vivo

experimental ulceration in rats and anti-H.pylori in vitro

 Gastro protection against necrotising agents and indometacin
Cardamom (Elettaria cardamomum Maton.) Crude methanolic extract and fractions Gastro protective use in Unani medicine Terpenes and phenolic compounds Experimental ulceration in rats Gastro protection against ethanol and aspirin-induced injury
Fenugreek (Trigonella foenum graecum) Aqueous extract of seed and gel fraction Gastric complaints Steroidal saponins and alkaloids Rat study Prevents ethanol-induced gastric lesions
Sangre de grado (Croton urucurana var. genuinus and related species) Red sap from trunk wood of C urucurana Gastric ulcer and diarrhoea Proantocyanidins, taspine Experimental study in rats and guinea-pigs Antiulcer, antidiarrhoeal and visceral antinociceptive effects
Copaiba oil (Copaifera langs dorffii Desf.) and related species) Oleo-resin from trunk wood Gastrointestinal disorders Volatiles and diterpenes that include kaurenoic acid In vivo

experimental studies with rats

 Antiulcer, wound healing and anti-inflammatory effects
Aroeira (Myracrodruon urundeuva Engl.) Aqueous extract from stem bark Traditional use in gastric dyspepsia, anc diarrhoea Tannins and Chalcones Experimental studies with rats and guinea-pigs Gastroprotection against ethanol, stress and histamine-induced lesions; acetic acid-induced colitis
Monkey puzzle (Araucaria araucana Mol.) Resin Mapuche Amerindian use to treat ulcers Labdane diterpenes and lignans Experimental studies with mice Gastroprotection against ethanol-HCl-induced lesions
Macela (Egletes viscosa L.) Ethanolic extract of flower buds and flavonoid, ternatin Gastric dyspepsia, diarrhoea and constipation Volatiles, flavonoid (ternatin) and diterpenes (centipedic acid and 12-acetoxy hawtriwaic acid) Animal studies Antiulcer, antidiarrhoeal and anti-inflammatory effects
Tsubaki (Camellia japonica L.) Methanolic extract of flower buds Blood vomiting and stomach ache Camelliosides Experimental studies in rats Decreased the ethanol and indometacin-evoked gastric ulceration
Mango (Mangifera indica L.) Aqueous decoction of mango flowers Gastrointestinal disorders and arthralgias Xanthone (mangiferin), flavonoids and triterpenes Acute and subacute models of gastric ulceration in rodents Decreased the acetic acid, ethanol and stress-induced gastric ulceration
Grape-seed (Vitis vinifera L.) Seed extract Gastro protection Proanthocyanidins Animal models of gastric ulceration Decreased the ethanol, stress, and indometacin-induced gastric ulceration
Karela (Momordia charantiaL.) Dried powdered fruits Traditionally used in diabetes and for healing of peptic ulcer Triterpenes and glycosides, karavilagenins and karavilosides Animal models of gastric ulceration Reduced ulceration
Almecega (Protium heptaphyllum March.) Resin from the trunk wood Traditionally used remedy in gastrointestinal disorders Volatiles and triterpenes (alpha-and beta-amyrin) Animal studies Antiulcer, visceral antinociceptive and anti-inflammatory effects of α- and β-amyrin
Coptis (Coptis Chinensis Franch.) Root extract Traditionally used remedy in gastrointestinal disorders Alkaloids (10% berberine) Animal studies Inhibits ulcer formation and acid secretion
Bone setter (Cissus quadrangularis L.) Methanolic extract Traditionally used for fracture healing Vitamin C and β- carotene Rat study Prevents indometacin-induced ulceration
Red sanders (Pterocarpus santalinus L.) Ethanolic extract Traditional herbal drug for wound healing 3-keto-oleanane Rat gastric ulceration model in vivo and anti-H. pylori in vitro Cytoprotection antioxidant, anti-H. pylori and antiulcer effects

STW 5 is composed of ethanolic extracts from nine plants (Ibera Amara Totalis, Angelicae Radix, Cardui Mariae Fructus, Carvi Fructus, Chelidonii Herba, Liquiritae Radix, Marticariae Flos, Melissae Folium, Menthae Piperitae Folium). N-095 is a mixture of red ginseng, polygala root, saffron, antelope horn and aloe wood.

Sangre de grado is derived from several Croton species (Croton dracanoides, Croton palanostigma, Croton lecheleri, Croton urucurana).

Baishouwu is an appellative name of dried root tubers from three Asdepiadaceae plants: Cynanchum auriculatum Royle ex Wight, Cynanchum bungei Decne and Cynoctonum wilfordii Maxim.

• suppressing the neutrophil/cytokine cascade in the gastrointestinal tract

• promoting tissue repair through expression of various growth factors

• exhibiting antioxidant activity, scavenging reactive oxygen species

• inhibiting cytochome P450 2F1 activity, producing antinecrotic and anticarcinogenic activities.

However, experimental studies have aimed mostly to validate the traditional use of plants in gastrointestinal disease, but no attempt has been made to verify their potential in functional dyspepsia.

Irritable bowel syndrome

IBS is a potentially debilitating condition characterised by abdominal discomfort, bloating, and disturbed patterns of defecation with a lower health-related quality of life. According to Rome III criteria, irritable bowel syndrome is defined as recurrent abdominal pain or discomfort for at least 3 days per month. It affects approximately 15-30% of the general population. The prevalence is equally divided among three subtypes: irritable bowel syndrome with constipation, IBS with diarrhea, and irritable bowel syndrome with alternating constipation/diarrhea.

Conventional therapy includes the use of bulk laxatives and stool softeners for constipation, anti-motility drugs for diarrhea, and antispasmodics, antimuscarinics and antidepressants for pain and spasm. Chronic constipation is a very common disorder, and the goals in treating such patients are to improve the patient’s symptoms and to restore normal bowel function, aiming to achieve at least three bowel movements per week. Serotonin plays a prominent role in chronic constipation, since it affects the intestinal motility, fluid secretion and sensation through activation of receptors present in enterochromaffin cells.

The only FDA-approved agents for chronic idio-pathic constipation are tegaserod (5-HT3 agonist) and lubiprostone, a type 2 chloride-channel activator, which both represent real therapeutic advances in the management of these patients. Lubiprostone draws chloride, sodium, and water into the lumen of the gut enhancing fluid secretion and facilitating increased motility and colonic transit. Lubiprostone, although significantly better than placebo in improving symptoms of constipation severity, stool consistency, straining, and abdominal discomfort, has been shown to be associated with adverse events such as nausea (30.2%), diarrhea (19.2%) and distention (9.3%). However, patients are refractory to these agents in the presence of pelvic floor dyssynergia, leaving the option for therapy with a prokinetic agent, fibre or a laxative. Thus, there is an overall dissatisfaction with traditional treatment options from patients and physicians.

Clinical studies with herbals in functional gastrointestinal disorders

In the recent past, a few controlled clinical studies were carried out with phytotherapeutic combinations (i.e. combinations of various plant/herbal extracts with a number of different active ingredients) which showed superiority over the placebo treatments (Table: Clinical studies with herbal medicinals in gastrointestinal functional disorders). However, randomised controlled trial (RCTs) data supporting the efficacy of these treatments in patients with functional gastrointestinal disorders (FGIDs) are still lacking. RCTs indicated that peppermint oil could be efficacious for symptom relief in irritable bowel syndrome and meta-analysis confirmed this. Placebo-controlled RCTs demonstrated the clinical efficacy and safety of a polyherbal preparation, STW 5 (Iberogast, Enzymatic Therapy Inc.) for the treatment of both functional dyspepsia and patients with irritable bowel syndrome. The pharmacological effects, as well as the therapeutic effectiveness, tolerability, and toxicity, of Iberogast were experimentally and clinically recorded and documented. These studies indicated that Iberogast promotes gastric relaxation and stimulates antral motility. Tong-xie-ning, a standard Chinese traditional herbal formula, and Padma Lax, a Tibetan herbal medicine, showed significant improvement of global symptoms in FGID, when compared with placebo treatment. An RCT assessing artichoke leaf extract in 247 patients with functional dyspepsia demonstrated a significant improvement in both overall symptoms and disease-specific quality of life compared with placebo.

Table: Clinical studies with herbal medicinals in gastrointestinal functional disorders

Name Part used Use Constituents Study type Results
STW 5 lberogast® (herbal formula) Ethanolic extracts of 9 plants Functional dyspepsia and IBS Methionine like sulphur-compounds Placebo-controlled RCT Improved gastrointestinal symptom-severity score
Carmint Total extracts of 3 plants Irritable bowel syndrome (IBS) (E)-2-dodecenal, eugenol, menthol and L-carvone Pilot clinical study Reduced the severity and frequency of abdominal pain/ discomfort
Tong-xie-ning (TCM-herbal formula) Dried extract of four herbs Diarrhoea-predominant IBS Complex compound containing paeoniflorin Placebo-controlled RCT Reduced symptom severity
Hange-koboku-to (HKT, Kampoo medicine) Dried mixture of 5 crude herbs Functional dyspepsia Magnorol, konokiol, perillaldehyde, 6-gingerol, 6-shogaol Open clinical study Improves delayed gastric emptying (prokinetic effect)
Padma Lax (Tibetan herbal medicine) Dried extract from 10 plants Constipation-predominant IBS Multicomponent Double-blind randomised pilot study Reduced symptom severity
Artichoke (Cynara scolymus L.) Leaf extract Dyspepsia and IBS Caffeoylquinic acids and flavonoids Open clinical study Amelioration of global symptoms and improvement in QOL score
Peppermint (Mentha piperita L.) Leaf essential oil Irritable bowel syndrome (IBS) Menthol and menthonin Double-blind RCT Smooth muscle relaxation; analgesia
Turmeric (Curcuma longa L.) Rhizome extract IBS; ulcer and non-ulcer dyspepsia Curcumin (diferuloyl methane) Placebo-controlled RCT Improved healing of peptic ulcer and of non-ulcer dyspepsia but not of IBS
Red pepper (Capsicum annuum ssp.) Powder Functional dyspepsia Capsaicin Placebo-controlled RCT 60% Reduction of symptom score
Mangava-brava (Lafoensiapacari St Hil.) Methanolic extract Used in gastric ulcer and inflammatory conditions Ellagic acid Double-blind RCT against H. pylori Well tolerated and patients were symptom-free in an 8-week trial

STW 5 is composed of ethanolic extracts from nine plants (Ibera AmaraTotalis, Angelicae Radix, Cardui Mariae Fructus, Carvi Fructus, Chelidonii Herba, Liquiritae Radix, Marticariae Flos, Melissae Folium, Menthae Piperitae Folium).

Carmint contains total extracts from three plants (Melissa officinalis, Mentha spiccata and Coriandrum sativum).

Tong-xie-ning consists of dried substances of Paeonia lactiflora Pali, (root), Atractylodes macrocephala Koidz. (rhizome), Citrus reticulata Blanco, (unripe exocarp) and Allium macrostemon Bge. (bulb).

HKT is a composite of five crude herbs: Pinelliae Tuber, Hoelen, Magnoliae Cortex, Perillae Herba and Zingiberis Rhizoma.

Padma Lax is composed of Aloes, Calumba, Cascara, Myrobalan, Condurango, Elecampane, Frangula, Gentian, Pepper and Nux vomica.

RCT = randomised, controlled trial; QOL = quality of life.

Studies on curcumin (diferuoylmethane), an ingredient of turmeric (Curcuma longa) demonstrated improvement in healing of peptic ulcer and symptoms in non-ulcer dyspepsia but not in irritable bowel syndrome. Capsaicin, the active ingredient of another spice, red chilli pepper, has been evaluated in small RCTs, which yielded conflicting results in patients with functional dyspepsia. While one study reported significant improvement in overall symptoms, epigastric pain, fullness and nausea compared with placebo, an earlier placebo-controlled crossover trial was unable to show significant improvements in postprandial dyspepsia scores with capsaicin.

The combination of extracts of different plants appears to be advantageous to treat functional gastrointestinal disorders (FGIDs) compared with conventional chemically well-defined drugs. Nevertheless, several issues regarding herbal products deserve mention. Based on current evidence, the scientific validity of the use of many of these commercial natural products in FGIDs is severely limited, with quality control and regulatory issues continuing to be a concern. The available trials almost all suffer from significant methodological flaws making the results difficult to interpret. Although the short-term use appears relatively safe, the long-term safety of these agents has not been established. Further, because these natural products are not regulated as pharmaceuticals, questions regarding agent purity and potency could be raised.

Safety and efficacy issues

The quality of herb used and its chemical constitution is fundamental to understanding the product’s intended use and factors affecting its safety. It is the chemical constituents that are the basis for the pharmacological activity of a herbal product, and consequently for the therapeutic efficacy. Use of validated, reliable, and relevant methods for efficacy/toxicity studies with regulatory strategies are essential to create a stronger evidence base on the safety, efficacy and quality of the herbal products for functional gastrointestinal disorders.

Evaluation of herbal medicines: preclinical studies

Preclinical assays are essential to guarantee the safety and efficacy of natural products in functional gastrointestinal disorders (FGIDs). The pathophysiology of FGID is not firmly established, and is characterised by recurrent episodes of gastrointestinal symptoms with no structural alterations. Visceral hypersensitivity, disordered gastrointestinal motility and secretion are presently considered key mechanisms underlying FGID symptoms. Therefore, pharmacological studies with new herbal products for efficacy and safety assessment are carried out using in-vitro and in-vivo experimental models that helped define basic mechanisms of functional dyspepsia and IBS symptoms. Animal testing should follow the ethical considerations and the approval of the Institutional Committee on the Use of Animals for experimentation.

In-vitro and animal testing

The emerging therapies for functional gastrointestinal disorders are largely aimed at normalising pain perception and gastrointestinal motor and reflux function. Helicobacter pylori infection, NSAID consumption and severe physical stress are associated with FGID. For this reason, the most common pharmacological properties determined in the evaluation of drugs effective for FGID are the anti-Helicobacter, cytoprotection, visceral analgesic, spasmolytic, antisecretory, antidiarrheal and prokinetic effects. The requirement for each one of these studies include experimental animals (two species, one rodent and another non-rodent, 6-8 per group), appropriate controls (negative and positive), and product evaluation at three dose levels.

H. pylori may induce gastritis and chronic dyspepsia (functional non-ulcer dyspepsia or gastro-duodenal ulcer) in humans. Mongolian gerbils or BALB/c mice infected with H. pylori are often used as animal models to screen test compounds for their efficacy in reducing the extent of gastric ulceration or inflammation. Although these animals demonstrate gastric ulceration, virtually no gastritis is seen in the antrum of infected animals, but this is, however, the hallmark of human infection. The anti-H. pylori activity of a test drug can be assessed through in-vitro studies employing rat gastric epithelial cell cultures and H. pylori isolates from gastric mucosal biopsy patients. The minimum inhibitory concentration value of test drug is first established against H. pylori and then H. pylori is co-cultivated with rat gastric epithelial cells in the presence/absence of test drug at its minimum inhibitory concentration. A reduction in the activity of urease, a normal appearance of the epithelial cells on electron microscopic examination, a decrease in lipid peroxidation and lactate dehydrogenase suggests the possible anti-H. pylori activity of PS.

Gastric cytoprotection can be evaluated using rat/mouse/guinea pig models of gastric lesions induced by absolute ethanol, indometacin, histamine and immobilisation stress and, to elucidate the physiological mechanism, effects of herbal products on mucus secretion, acid secretion (pylorus-ligated animals), glutathione reserve, mucosal blood flow and gastric emptying time are analysed. In addition, to understand the pharmacological mechanism underlying the gastroprotection, the role of capsaicin-sensitive fibres, endogenous prostaglandins and nitric oxide may be verified, using capsaicin-desensitisation procedure, and/or analysis of prostaglandins by ELISA and nitrite/nitrate by Griess reaction or indirectly by the use of nitric oxide synthase inhibitors.

Visceral hyperalgesis is a characteristic feature of functional dyspepsia and irritable bowel syndrome. Visceral antihyperalgesic effects of herbals can be examined using animal models of nociception induced by intracolonic administration of mustard or capsaicin. These chemicals evoke both inflammatory and non-inflammatory pain through sensitisation of neurones at the peripheral and/or central sites, involving several neuropeptides and a great variety of inflammatory mediators. They serve as valuable tools in assessing gut pain and to study the possible mechanism.

Spasmolytic and antidiarrheal properties of test compounds can be assessed in well-established models such as the USSING-chamber, a pharmacological model for diarrhea, and the isolated guinea pig ileum, a model for modulatory effects on ileum contraction. The inhibitory effect observed in these models provides ex-vivo evidence for the spasmolytic and antidiarrheal activities of herbal products. Several studies have investigated abnormalities of serotonin signalling in IBS. Decreased postprandial serotonin plasma levels have been reported to occur in constipation-predominant IBS, and increased plasma levels have been reported to occur in diarrhea-predominant irritable bowel syndrome.

To verify the potential usefulness of herbals in diarrhea-prone IBS, in-vivo testing could be carried out in mice on castor oil- or croton oil-induced diarrhea, cholera toxin-induced intestinal secretion and on gastrointestinal transit induced by 5-HTP, using alosetron, an antagonist for 5-HT3 receptors and a known agent effective for diarrhea-predominant irritable bowel syndrome as a positive control. Further, morphine-induced gastrointestinal delay in mice may be used as a model to test the compound’s likely use in constipation-predominant IBS, using tegaserod, a 5-HT4 receptor agonist, as a positive control. Tegaserod is a known prokinetic agent that speeds small-bowel transit and right-colon transit in irritable bowel syndrome, reducing symptoms of constipation, pain and bloating.

Safety pharmacology

Clinical assessment of the gastrointestinal tract is often limited to measurements of transit time and observations of vomiting or diarrhea. In-vitro functional human tissue assays can be performed to measure a vast range of toxic effects of drugs under investigation, at the level of the organ, cell or even gene and these assays are considered an important adjunct to routine safety pharmacology tests. The cytotoxicity of new compounds can be determined by the MTT reduction assay using human lung fibroblasts (MRC-5). These models are rapid, less expensive and reveal mechanisms of action. The data obtained serve as signals of potential harmful effects in humans and are often superior to extrapolation from animals. The heart is a frequent site of toxicity of pharmaceutical compounds in humans, and, when developing a new drug, it is critical to conduct a thorough preclinical evaluation of its possible adverse effects on cardiac structure and function. Changes in cardiac morphology such as myocardial necrosis, hypertrophy or valvulopathy are assessed in laboratory animals. The potential proarrhythmic risk of new drugs is a major subject of concern and needs to be fully addressed before treatment of volunteers or patients takes place. The recommended tests to detect most arrythmic drugs were to determine the effects on cardiac ion channels, in particular I(Kr) potassium channel antagonism in vitro and prolongation of the QT interval, assessed in vivo, in telemetred dogs.

In-vivo animal safety data serve as important signal generators and in some cases, may stand alone as indicators of unreasonable risks. These include acute toxicity, and long-term toxicity, reproduction toxicity, genotoxicity and carcinogenicity studies. Knowledge of an ingredient’s pharmacokinetics and in-vivo metabolism will allow most appropriate interpretation of relevancy of the dose/concentration used in the in-vitro tests. Evidence of abnormalities from laboratory animal studies can be indicative of potential harm to humans.

Acute toxicity testing involves the study of toxic effects after a single (oral/parenteral) administration of the test compound with the objective to classify the substance associated on the basis of acute toxicity, identification of target involved in the acute toxic effect (signs: time of appearance, progression and reversibility), and to establish the dose intervals that may be of relevance to other toxicological studies. A long-term toxicity study (4-12 weeks) involves the repeated doses of the test substance, aimed to determine the maximum tolerable dose, the highest dose that does not result in toxic effects and the mechanism underlying the toxic effects in vivo by means of biochemical, behavioural and histopathological studies. Genotoxicity and carcinogenesis studies are important because several medicinal plants contain substances such as pyrrolizidine alkaloids, flavonoids, phorbol esters, etc., which can cause mutagenic effects. The Ames test using Salmonella typhimurium strains and the CHO (Chinese hamster ovary) chromosomal aberration test are the two most commonly used methods for the evaluation of genetic mutation and chromosome damage.

Evaluation of herbal medicines: controlled clinical trials

The choice of primary endpoint for a clinical trial is to demonstrate the efficacy of a therapeutic agent.

The Rome III Committee recommends two types of measures to assess the efficacy of new treatments for irritable bowel syndrome and functional dyspepsia:

• binary endpoints addressing the construct of relief (that is, adequate relief and satisfactory relief)

• an integrative symptom questionnaire that addresses the change in severity of a representative group of symptoms of irritable bowel syndrome (that is, the IBS Severity Scale).

The current evidence suggests that at present, adequate relief should be recognised by regulatory authorities as an acceptable primary endpoint in clinical trials. This analysis also suggests that data from individual clinical trials should be pooled and undergo meta-analysis, and that prospective studies should be considered to further characterise the performance of available endpoints as outcome measures in pharmacotherapeutic trials. Literature search reveals that few well-controlled, double-blind (placebo-controlled) trials have been carried out with herbal medicines (see Table: Clinical studies with herbal medicinals in gastrointestinal functional disorders). Meta-analyses of reviews published reveal several discrepancies, and these are mostly due to:

• lack of standardisation and quality control of the herbal drugs used in clinical trials

• use of different dosages of herbal medicines

• inadequate randomisation in most studies, and patients not properly selected

• numbers of patients in most trials insufficient for the attainment of statistical significance

• difficulties in establishing appropriate placebos because of the tastes, aromas, etc.

• wide variations in the duration of treatments using herbal medicines.

A few herbal products, e.g. STW 5 (Iberogast), Artichoke, Carmint, Tong-xie-ning (Chinese herbal formula), Hange-koboku-to (Kampoo medicine), and Padma Lax (Tibetan herbal medicine) have been evaluated in clinical trials, but they still have the difficulties mentioned above and need additional, well-controlled and appropriate randomised clinical trials to prove their efficacy.

To assess the efficacy of new herbals in functional gastrointestinal disorders, a double-blind, randomised, placebo-controlled, parallel group trial remains the preferred design. Investigators should include as broad a spectrum of patients as possible and should report recruitment strategies, inclusion/exclusion criteria, and attrition data. The primary analysis should be based on the proportion of patients in each treatment arm who satisfy a prespecified clinically meaningful change in a patient-reported symptom-improvement measure. Such measures of improvement are psychometrically validated subjective global assessments or a change from baseline in validated symptom guidelines and include an analysis of harms data and secondary outcome measures to support severity questionnaire. Data analysis should address all patients enrolled, using an intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials or explain the primary outcome. Trials should be registered in a public location, prior to initiation, and should be reported even if the results are negative or inconclusive.

Conclusions

No standard therapy is currently available for functional gastrointestinal disorders such as functional dyspepsia and irritable bowel syndrome, which are characterised by multiple symptoms associated with disordered gut function. There is limited evidence for the efficacy, safety and tolerability of currently available conventional therapies and it may be that, with traditional herbal therapies, patients may respond better in symptom improvement because of their multicomponent nature with different active constituents having pleotropic actions. However, herbal medicinals should undergo the same procedures as conventional drugs and should not be considered differently because they are of natural origin. Preclinical studies on very many herbal extracts and their active constituents demonstrated interesting pharmacological properties relevant to functional dyspepsia and irritable bowel syndrome, but only few of them were taken to clinical trials with limited success. Future studies should address their effectiveness and safety in patients with FGIDs by the double-blind, randomised, placebo-controlled, parallel-group trial study design. The safety and their quality should be ensured through greater pharmacovigilance studies and by governmental regulatory mechanisms. To provide uniform quality of raw material, emphasis must be laid on domestication, production and biotechnological studies and genetic improvement of medicinal plants to provide uniform and high-quality raw material.

Pregnancy

Pregnancy and nutritional requirements

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August 25, 2010 at 12:44 pm

Normal conception, embryonic development, and fetal development depend on the medical history, lifestyle, and nutritional state of the mother. While healthy babies can be born to women who are poorly fed, pregnancy and lactation often leave the mother with drained reserves and jeopardized health, and there is a greater probability of a high-risk birth.

According to the Food and Nutrition Board of the National Academy of Sciences, weight gain during pregnancy is now viewed as 25 to 35 lb. for women of average weight for height. A desirable weight gain should be worked out between the pregnant woman and her physician. The weight gain aids fetal growth and lowers the risks of low birth weights, infant mortality, and developmental problems. A large amount of new tissue is built and major changes occur in the mother’s body to accommodate growth and developmental problems. A large amount of new tissue is built and major changes occur in the mother’s body to accommodate growth and development of the placenta and fetus. Of the weight gained, one-third is converted to fetal tissue (6 to 8 lb.; the remainder forms the placeta (1 to 5 lb.), extra blood (3 to 4 lb.), enlarged breasts (1 to 2 lb.), enlarged uterus (2 lb.) and increased maternal fat stores (about 10 lb. [4.5 kg]). The weight gained during pregnancy is distributed among protein, fat, water, and blood.

Protein

The rate of protein synthesis remains high throughout embryonic and fetal development, although most of the fetal growth occurs in the last three months of pregnancy. Tissues like the brain, heart, and liver are composed mainly of protein (excluding water). New protein represents a net gain that is a positive nitrogen balance. There is an apparent correlation between maternal low blood protein levels and the risk of toxemia of pregnancy, which is associated with high blood pressure and protein loss in the urine.

Fat

A gain of nearly 10 lb. of body fat is equivalent to 47,500 calories. This provides an ample energy reserve for the mother and fetus and for lactation.

Water

Typically, about 60 percent of the gained weight is water. All new tissues require water because it is the principal constituent of the body and body fluids. Water is also stored as a fluid reserve to compensate for blood loss at childbirth. About 40 percent of pregnant women will retain excess water. The maternal blood volume increases by 30 percent, and the number of red blood cells increases by 18 percent. Maternal blood supplies the embryo and fetus with nutrients, including amino acids for protein synthesis and glucose and fatty acids for energy.

Nutritional Requirements

Protein

Dietary protein supplies amino acids, the raw materials for new protein. An estimated 1.3 g, 6.1 g, and 10.7 g of protein/day are required for the first, second, and third trimesters, respectively. Therefore, an additional 10 g/day above the adult requirement of 50 g/day throughout pregnancy is thought to meet the needs of most healthy pregnant women. The recommended dietary allowance (RDA) for protein during pregnancy is 60 g per day.

Calories

Metabolic changes occur that favor weight gain. Hormonal balance changes to maintain high blood glucose, amino acids, and fatty acids to store fat while slowing maternal utilization.

Calcium, Phosphorus, and Vitamin D

The RDA for calcium is 1,200 mg daily; the RDA for phosphorus is 1,200 mg and the RDA for vitamin D is 10 meg. The rate of calcium absorption jumps in the last two months of pregnancy to accommodate skeletal growth of the fetus; an infant at birth possesses nearly 30 g of calcium, mainly in bone. Dietary calcium may be better absorbed during pregnancy. However, it is important that the mother receive enough dietary calcium from conception until the end of lactation, and a calcium intake of 1,200 mg/day is advised. Although the amounts of phosphorus required for health are unknown, the total allowance should match that of calcium (1,200 mg/day). Vitamin D is required for calcium uptake and assimilation. Whether pregnancy increases the vitamin D requirement is not proven; however, the RDA for vitamin D is set at 10 meg/day for pregnant and lactating women. Early deposition of this fat-soluble vitamin provided in a balanced diet provides a reserve for later use when growth is very rapid.

Iron

Extra iron is required during pregnancy for increased production of red blood cells, to supply the fetus and placenta and to cope with blood loss during delivery. In the first trimester, cessation of menstruation compensates for additional needs of iron. To assure adequate iron throughout pregnancy, women need at 30 mg/day; this represents an additional 15 mg above the normal adult level. This high amount of iron cannot be supported by the usual American diet or by stored iron, so iron supplements are required. Because women do not menstruate during breast-feeding, iron requirements during lactation are essentially the same as those for nonpregnant women.

Folic Acid

Pregnancy increases the risk of deficiency when the intake of this fragile, water-soluble vitamin is marginal. The RDA for folic acid is 400 meg during pregnancy. To meet this requirement, vigilance is necessary in selecting foods. Evidence indicates that folic acid supplementation before conception and during the first months of pregnancy significantly reduces the risk of neural tube defects. (Federal agencies now recommend that women who are considering pregnancy as well as those who are pregnant consume 400 meg of folic acid daily.) During the first six months of lactation, the maternal RDA is 280 mg/day. The requirements for certain other nutrients also increase during pregnancy and breast-feeding (the following comparisons are made relative to the RDAs for nonpregnant adult women):

Vitamin A

Although the RDA does not increase during pregnancy, a 1.6-fold increase in the RDA during lactation is recommended (total of 1,300 meg of retinol).

Vitamin E

A 20 percent increase in the RDA during pregnancy, to 10 mg/day, is recommended. A 1.6-fold increase during the first six months of lactation, to 12 mg/day, is recommended.

Vitamin C

Pregnancy calls for a 17 percent increase in the RDA to 70 mg/day. The RDA during lactation is 95 mg/day.

Thiamin

A 50 percent increase in the RDA during pregnancy has been set at 1.5 mg/day. The RDA during lactation is about the same, 1.6 mg/day.

Riboflavin

There is a 23 percent increase during pregnancy to 1.6 mg/day. A 38 percent increase in riboflavin intake to 1.8 mg/day during lactation is recommended.

Niacin

Pregnancy entails a 13 percent increase in the RDA of niacin to 17 mg/day. A 23 percent increase during lactation to 20 mg/day is recommended.

Vitamin B6

The RDA increases by 38 percent during pregnancy, to 2.2 mg per day. During lactation RDA increases to 2.6 mg per day.

Magnesium

The RDA increases to 300 mg daily during pregnancy. During lactation the RDA is 35 5 mg/day.

Zinc

The RDA increases by 25 percent during pregnancy to 15 mg per day. During lactation the requirement is 19 mg/day.

Iodine

The RDA increases by 17 percent to 175 meg daily. During lactation the RDA is 200 meg.

Selenium

The RDA increases by 18 percent to 65 meg/day. During lactation, the RDA is 75 meg.

Possible nutrition-related problems during pregnancy are:

• Anemia: Inadequate functional red blood cells are the end product of a chronic deficiency, most frequently of iron, though deficiencies of protein, copper, and vitamins like folic acid, vitamin B6, vitamin E, vitamin C, or vitamin B12 may cause anemia.

• Constipation: A decrease in muscle tone and the pressure of the growing fetus can cause constipation. Adequate water intake and fiber, in the form of vegetables, whole grains, and fresh fruit, are recommended.

• Diabetes: Certain hormones increase during pregnancy that counteract insulin, the hormone that lowers blood glucose, promoting glucose uptake by tissues. This can lead to gestational diabetes, which can cause placental malfunction, oversized infants, and labor complications.

• Excessive weight gain: There is no ideal body weight and weight does not indicate nutritional status. Too rapid weight gain can be caused by high-fat, high-calorie food that is low in important nutrients. Food choices need to be nutrient dense, that is, they need to contain a high percentage of vitamins, minerals, and fiber relative to calories. A major effort to lose weight during pregnancy can cause abnormal mental development in infants.

• Preeclampsia: This disorder affects about 7 percent of women in the third trimester of pregnancy. Water retention (edema), elevated blood pressure, and passage of protein in urine are signs of the more dangerous condition, toxemia, which threatens both the mother and fetus. Salt restriction and the use of diuretics can be hazardous and require medical supervision. The incidence of toxemia has declined with better prenatal care. High-quality protein is essential during pregnancy.

• Heartburn: stomach acid may be forced up into the esophagus by the enlarged fetus. Small, frequent meals may help avoid this problem. Pregnant women should avoid foods that cause digestive problems.

• Inadequate weight gain: Mothers whose nutritional deficiencies are corrected are more likely to have normal-term pregnancy and normal births.

• Drug and alcohol use; smoking: Studies of fetal alcohol syndrome suggest that there is no safe dose of alcohol during pregnancy. It has been suggested that alcohol may be one of the most common cause of birth defects and mental retardation in the United States. The use of cocaine, heroin, and addictive drugs during pregnancy leads to drug addicted infants who experience severe withdrawal symptoms at birth. Mental disturbances such as irritability and problems with social adjustment can continue throughout childhood and into adult life. Smoking is associated with reduced birth weight because carbon monoxide in cigarette smoke reduces the oxygen supply to the fetus. Many medications pass through the placenta and adversely affect the fetus. No medication or nutritional supplement should be taken during pregnancy without medical supervision.

Allen, Lindsay. “Anemia and Iron Deficiency: Effects on Pregnancy Outcome,” American Journal of Clinical Nutrition 71 (2000): 1,280S-1,284S.

Dictionary

Blood

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August 23, 2010 at 8:47 am

The cell-filled liquid that circulates through the heart, arteries, and veins. A 70 kg adult has a blood volume of 5 liters. Blood is regarded as a tissue in which red and white cells are suspended in a liquid (plasma) in the ratio of 45 parts cells to 55 parts plasma. This vital fluid performs many tasks. Blood supplies all tissues with nutrients and oxygen, and it transports waste such as urea to the kidneys, and carbon dioxide to the lungs, for disposal. Blood is the medium for integration and coordination of tissues of the body through hormonal regulation. It maintains the chemical equilibrium of the body in terms of electrolytes (ionic substances) and polyelectrolytes (serum proteins), which in turn regulate water distribution in blood versus tissues. Blood pH is buffered to maintain a very narrow range at 7.35 to 7.45. Circulating antibodies, gamma globulin, represent blood aspects of the immune system and thus are the first line of defense against foreign substances. Blood also contains special cells, platelets, and protein clotting factors to form clots and thus limit blood loss. Fats, cholesterol, and fat-soluble vitamins are transported in the blood by specialized structures (lipoproteins). Nutrients like vitamin A, iron, and copper are carried by their own transport proteins. In terms of mechanical function, the bloodstream assures an even temperature for all regions of the body.

Most cells in blood are red blood cells (erythrocytes), which are specifically designed to transport oxygen, white blood cells (leukocytes) represent a much smaller fraction; as part of the immune system they protect against infection. Lymphocytes, which represent 20 percent to 50 percent of white cells, are derived from either bone marrow or from the thymus gland. They mount a cellular defense against foreign cells and materials. Plasma, the fluid remaining once cells are removed, contains fibrinogen. This inactive protein can be activated to form fibrin clots to plug holes in blood vessels. The fluid remaining after blood has clotted is called serum which lacks cells and clotting factors, but contains glucose and minerals like potassium, sodium, and chloride, the most common electrolytes. These ions help maintain the appropriate ionic strength, pH, and fluid balance of the body. Serum contains albumin and other proteins that help maintain ion concentrations in the blood, and it contains transport proteins, such as very low-density lipoproteins (VLDL) for carrying fat and low-density lipoproteins (LDL) and high-density lipoproteins (HDL) to transport cholesterol.

Several types of nutrients support the circulatory system. For example, vitamin k and calcium support the blood clotting mechanism, zinc, iron, manganese, magnesium, vitamin B6, folic acid, vitamin B12, and other nutrients support erythrocyte and leukocyte production. Vitamin C maintains strength and elasticity of capillaries. (See also blood clotting; endocrine system; hemoglobin; immune system.)

Blood-brain barrier

A structural barrier that limits the passage of a variety of substances, including certain drugs and nutrients, from blood vessels into the brain and the central nervous system. This barrier consists of cells lining capillaries (endothelial cells). The attachments between these cells are called “tight junctions.” However, the nature of the physical barriers and biochemical mechanisms for transporting materials across the barrier are complex and are not completely understood. Very small molecules like water and oxygen simply diffuse through cells and capillaries, glucose, the major fuel of the brain, is an example of a substance that can penetrate the blood-brain barrier, passing freely across the barrier, though other sugars do not. During starvation or crash dieting, ketone bodies, small acidic compounds that accumulate in the blood during excessive fat degradation (a condition known as ketosis), can cross through capillary linings, pass into the brain and be burned for energy. In contrast, long-chain fatty acids that make up fat cannot penetrate the blood-brain barrier, and consequently fat cannot supply the brain with energy. Some nutrients rely on transport systems embedded in cell membranes to actively transport substances into the brain. Thus amino acids enter by specific, energy-dependent processes (active transport) tyrosine, phenylalanine, leucine, isoleucene, valine, and tryptophan compete for the same transport sites. Different sites are specific for other types of amino acids. (See also food; neurotransmitter.)

Blood pressure

The pressure maintained in arteries and veins by the heart. Blood pressure usually refers to an indirect measurement of pressure of large arteries at the height of the pulse. Blood pressure reflects the resistance of blood flow in the capillary bed and arterioles as well as the elasticity of arteries themselves. The heart exerts pressure throughout the circulatory system. Ventricles of the heart contract (the systolic phase of the heartbeat), creating systolic pressure in the cycle of heart pumping. Ventricular relaxation between heartbeats creates the lowest pressure between heartbeats, the diastolic pressure. Like a barometer for measuring air pressure, blood pressure is measured in units equivalent to the height of a column of mercury. A pressure of 120/80 represents a systolic pressure equivalent to 120 mm of mercury and a diastolic pressure of 80 mm of mercury. A systolic pressure persistently greater than 140 and a diastolic pressure persistently greater than 100 indicate stages of hypertension (high blood pressure), a potentially serious condition.

The following factors are linked to increased blood pressure: overweight, age, emotional stress, physical activity, and male gender. Quiet sleep and female gender are linked to with decreased blood pressure.

Dietary factors and heredity are risk factors for susceptible individuals. Approximately 20 percent of adults will be adversely affected by overconsumption of sodium. Unfortunately, these salt-sensitive individuals cannot be readily identified. Eating a large meal can lower blood pressure quickly in older people when the stomach fills with food, and experiments show that such people may feel faint or have an angina attack unless they lie down. (See also heart disease.)

Blood clotting

The formation of a semi-solid mass from blood constituents. Exposure of blood to air, to foreign substances or to substances released from injured tissues (thromboplastin) stimulates blood clotting. Blood clotting is a complex process requiring the sequential activation of a series of clotting factors, which are protein modifying (proteolytic) enzymes. It culminates in the activation of thrombin, the terminal enzyme that catalyzes the conversion of fibrinogen, a soluble blood protein, to insoluble fibrin. Fibrin forms fibers that create a sticky mass that enmeshes blood platelets, a very small type of white blood cell, and red blood cells. This mass of fibers and cells forms a plug that covers the injured region of a capillary. The platelets fragment and release serotonin, a compound that causes the capillary to contract and the blood clot to retract. The net result is that the hole is patched and blood flow is reduced at the site of injury.

Nutrition status affects blood clotting. The maturation of prothrombin, the parent molecule of thrombin, and of other blood clotting factors (proenzymes) further up the clotting sequence of reactions, requires vitamin k and calcium. A calcium deficiency effectively slows the activation of clotting enzymes because a calcium-prothrombin complex must first form in order to be activated to thrombin. Vitamin K deficiency slows clotting because prothrombin cannot be modified to bind calcium, starvation and protein malnutrition reduce clotting because the liver synthesizes lesser amounts of the protein clotting factors and fibrinogen.

Blood sugar

The level of glucose in the blood. red blood cells and most of the nervous system, including the brain, rely on this fuel to meet most of their energy requirements. The body strives to maintain blood sugar at a constant level. This reflects hormonal regulation and a delicate balance between diverse processes: carbohydrate digestion and assimilation; tissue uptake of glucose; and release of glucose by the liver. During the fasting state, blood sugar levels remain relatively constant for an individual; the normal range of fasting blood sugar is 60 to 100 mg per 100 ml.

What Happens After a Meal?

Typically, blood sugar levels rise an hour or so after a meal containing carbohydrate, as the glucose produced by digestion of starch and complex sugars is absorbed by the intestine. Elevated blood sugar after a carbohydrate meal signals the endocrine pancreas to release insulin. This hormone lowers blood sugar by stimulating most tissues to take up glucose and metabolize it. The absorbed glucose is either stored as glycogen in muscle and liver, or it is converted to fat by the adipose tissue and the liver. As a result, blood sugar levels return to base line values several hours after eating.

What Happens Between Meals (Fasting)?

Glucose is constantly being consumed by the brain and other tissues. In response to a drop in blood sugar or to stress, the adrenal glands release cortisol and epinephrine and the pancreas releases glucagon. These hormones signal the release of glucose from glycogen stores in the liver, and the synthesis of glucose from amino acids, by the liver, raising blood sugar levels to base line values.

Hypoglycemia refers to a sustained, abnormally low blood glucose level. If blood sugar drops too low, the brain does not function normally. This condition creates mood changes, irritability, fainting, and fatigue. Reactive hypoglycemia refers to a drop in blood sugar levels that can occur several hours after eating. This is usually due to the abnormal functioning of insulin (dysinsulism). Severe hypoglycemia due to profound metabolic imbalances can lead to coma.

Hyperglycemia (elevated blood sugar) is at the other extreme and is characterized by sustained, elevated blood glucose as observed in diabetes mellitus. Chronic high blood glucose, frequent in uncontrolled diabetes, has many unfortunate ramifications. It can lead to the destruction of peripheral nerves and eye damage; lowered resistance to infections; toxemia during pregnancy; and heart and kidney disease. The excretion of excess sugar in the urine causes dehydration.

Lifestyle choices can help stabilize blood sugar levels and thus minimize wide swings in the changes brought about by the over- or underproduction of hormones. The body responds more efficiently to insulin with reduced intake of refined carbohydrates, coffee, and alcohol. Specific nutrients may help the body regulate blood sugar. Dietary chromium can help insulin work more effectively; stress, coffee, and sugar consumption deplete the body of chromium. High levels of biotin seem to assist the liver with carbohydrate and fat metabolism, niacinamide, niacin, vitamin C, vitamin B6, manganese, magnesium, zinc, and selenium have been shown to improve glucose tolerance in some instances.

Eating frequent, light meals that are high in protein often helps to avoid swings in blood sugar levels, and balanced meals with whole foods high in starch and fiber are effective time-released sources of glucose. Stress reduction with meditation, yoga or biofeedback, regular exercise, and maintaining optimal body weight, also helps minimize blood sugar imbalances. (See also dieting; gluconeogbnesis; glycogbnolysis.)

Gold, Paul E. “Role of Glucose in Regulating the Brain and Cognition,” American Journal of Clinical Nutrition, 61:supplement (1995): 987S-995S.

Dictionary

Antioxidants

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August 21, 2010 at 7:31 am

A compound that prevents or retards the oxidation of sensitive molecules found in the body or in foods. Antioxidants occur in many foods naturally as nutrients or non-nutrients, or as synthetic additives. Antioxidants typically block oxidation by preventing damage caused by free radicals, extremely reactive forms of oxygen and other molecules that lack an electron and tear electrons from molecules they meet. In the body, likely targets are DNA, proteins, and lipids (unsaturated fatty acids).

Free radicals form in the body by normal cellular processes. These include phagocytosis (engulfing viruses and bacteria) by immune cells; incomplete reduction of oxygen as mitochondria burn fuels; production of hydrogen peroxide by the breakdown of fatty acids and the generation of nitric oxide, a free radical that functions as a localized vasodilator, a defensive chemical and as neurotransmitter. Free radicals and reactive forms of oxygen occur by chemical modification of pollutants and toxic substances within the liver. Free radical damage may contribute to cancer, cardiovascular disease, and aging; consequently, antioxidants are a current focus of extensive medical research. It is intriguing that certain antioxidants are both anticancer nutrients and antiaging nutrients. Because there is such a large variety of reactive molecules and free radicals, the body requires a wide range of antioxidant defenses. A “pecking order” exists among antioxidants; some are more readily oxidized than others and will be consumed rapidly unless replenished or recycled in the body. Certain antioxidants are “preventive inhibitors,” that is, they block the initiation of free radical attack. Preventive inhibitors include defensive enzymes like catalase and glutathione peroxidase (destroy hydrogen peroxide and lipid peroxides) and superoxide dismutase (destroys superoxide), chelating agents like citric acid that lock up metal ions, proteins that bind metal ions, including albumin, transferrin, and ferritin. Other antioxidants, “chain breakers,” convert free radicals to stable (safe) products, vitamin e and vitamin c are essential chain-breaking antioxidants. It is worth remembering that under certain conditions, an antioxidant may become an oxidant. If the antioxidant becomes a free radical, then it, too, must be disarmed and regenerated.

Antioxidants as Nutrients

Vitamin A, beta-carotene, vitamin C, vitamin E, and selenium are key antioxidant nutrients.

Carotenoids, including beta-carotene, trap free radicals, while vitamin A helps guide normal tissue development. Inadequate carotenoid intake increases the risk of cancers of the lung, bladder, esophagus, stomach, colon, rectum, prostate, and skin. Studies indicate that when used alone, beta-carotene does not prevent cancer or heart disease. Indeed, there are hints that unless beta-carotene is protected by another antioxidant, such as vitamin E, it may actually increase damage. A multitude of studies indicates that the consumption of foods rich in carotenoids protects against cancer, cataracts, and cardiovascular diseases.

Vitamin C destroys water-soluble free radicals and protects against cancer. It is needed for a healthy immune system and it also speeds wound healing. Vitamin C also protects low-density lipoprotein (LDL) cholesterol from oxidation. Evidence for the role of vitamin C in reducing the risk of coronary heart disease is weak. Ongoing clinical trials may help decide whether vitamin C supplementation is beneficial for preventing heart disease. There is some evidence that high dietary vitamin C may lower the risk of several cancers, such as breast cancer and stomach cancer. Evidence does not indicate that high doses of vitamin C decrease cancer risk, however.

Vitamin E acts as a fat-soluble, free radical trap that seems to protect the brain from free radical damage and to partially reverse age-related decline of the immune system in experimental animals. In addition, vitamin E promotes the normal function of smooth muscle cells and reduces platelet adhesion to arterial cells, factors which could reduce the risk of atherosclerosis. Many population studies have found a reduced risk of coronary heart disease with increased intake of vitamin E. However, most clinical studies of vitamin E supplementation for several years found no benefit in reducing heart disease risk.

Selenium works together with vitamin E by helping an enzyme system (glutathione peroxidase) block free radical attack and to disarm reactive lipids. Selenium is also required for a healthy immune system. Selenium deficiency increases the risk of cancer of the esophagus, stomach, and rectum.

Antioxidants as Nonnutrients in Food

In addition to vitamins, trace minerals, fiber, and carotenoids, vegetables and fruits provide many other ingredients important for long-term health. Vegetables and fruits contain orange-red and yellow pigments called carotenoids. They include carotenes such as beta-carotene and lycopene (from tomatoes) and xanthophylls, oxygen-containing derivatives such as zeazanthin and lutein. Xanthophylls occur at high levels in dark green leafy vegetables. Though relatively few carotenoids serve as sources of vitamin A, they help protect the body as versatile antioxidants, and they enhance the immune system, complementing the actions of beta-carotene. Fruits, vegetables, seasoning, spices, and herbs (tea) possess a wide range of complex-molecules called polyphenols (flavonoids) and phenolic acids that are complex ring structures. Flavonoids include isoflavones (soybean), flavones (such as quercetin from tea, berries, fruits) and flavonones (such as naringenin and hesperidin from citrus), flavanonols (such as catechins, condensed and hydrolyzable tannins), anthocyanins (purple, red, and blue pigments of fruits and berries), coumarins (from citrus), ellagic acid (from grapes), and others. In general, flavonoids possess multiple properties; thus they can quench free radicals, inhibit inflammation, strengthen capillary walls, and reduce oxidative damage to serum cholesterol. The optimal intake of flavonoids and carotenoids is not known and the long-term effects of supplementation with large amounts of phytochemicals has not been studied. It should be pointed out that beta-carotene, vitamin C, and even vitamin E under the appropriate conditions can become oxidants (prooxidants). Certain flavonoids also exhibit prooxidant properties. Chelated (complexed) iron in the presence of vitamin C can generate free radicals spontaneously in the test tube and this could be a potential problem in the body with iron overload diseases. Finally, certain flavonoids can specifically block the thyroid hormone-generating enzyme in thyroid cells. As with many dietary constituents, a little may be beneficial, while a lot could be harmful.

Foods rich in vitamin A and beta-carotene and related carotenoids include orange-colored vegetables like carrots and squash plus dark green leafy vegetables like chard, kale, and spinach. Fresh fruit, frozen juice concentrate, and vegetables like green pepper and broccoli supply vitamin C. Vegetable oil, wheat germ, and nuts provide vitamin E. Selenium occurs in whole grains, seafood, cabbage, onions, and garlic. Fruits and vegetables also provide flavonoids.

Antioxidants Made by the Body

Glutathione is a sulfur-containing antioxidant present in very large amounts in the cytoplasm. Besides helping to keep proteins reduced, it assists amino acid transport, helps regulate the internal oxidation state of the cell, maintains vitamin E in a reduced state, and detoxifies potentially harmful substances.

Coenzyme Q assists mitochondria to burn fat and carbohydrate for energy and it functions as a lipid soluble membrane antioxidant together with vitamin E, which it protects. Coenzyme Q production declines with age and the heart may become deficient in this nutrient.

Uric acid is found in the blood. It is a nitrogen-containing waste product from the breakdown of DNA and RNA.

Citric acid, succinic acid, and other complex organic acids generated by metabolism can bind iron and copper, preventing them from catalyzing of free radical-generating reactions.

Melatonin, a hormone produced by the pineal gland, possesses strong antioxidant properties.

Bilirubin, a breakdown product of hemoglobin, acts as an antioxidant in blood.

Antioxidants as Food Additives

Antioxidants are extensively utilized to prevent or retard deterioration that produces off-flavors or color changes in foods, making them less appetizing or less nutritious. Oxidation can also be promoted by enzymes in foods when exposed to air. This explains why apples, bananas, pears, peaches, and potatoes darken after being sliced. The food industry often employs synthetic antioxidants, particularly butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ethylene diaminetetracetic acid (EDTA), and propyl gallate, as well as vitamin C, as preservatives to extend the shelf life of processed foods by preventing free radical damage.

Spontaneous oxidation of fats and oils in the presence of oxygen, sunlight, and metal ions causes rancidity unless blocked by antioxidants. (BHA) and BHT are used to prevent rancidity in fats and oils, particularly in baked goods like crackers and cookies. Their safety has been questioned. EDTA is a common additive in salad dressings, margarine, mayonnaise, sandwich spreads, pureed fruits, and vegetables, as well as cured shellfish, beer, and soft drinks. EDTA is judged to be a safe food additive. Propyl gallate retards spoilage of fats and oils and is often used with BHA and BHT to maximize their antioxidant effects. Several studies with experimental animals suggest that propyl gallate may cause tumors. A close relative of vitamin C, erythroboric acid, is a common antioxidant used in the preservation of processed meats such as bologna, frankfurters, and bacon, sulfites are used as antioxidants to prevent discoloration of fruit and vegetables. Spices and herbs, including thyme, rosemary, and sage, are sometimes used as food additives to retard spoilage. (See also atherosclerosis.)

Fairfield, K. M., and R. H. Fletcher. “Vitamins for Chronic Disease Prevention in Adults.” Journal of the American Medical Association 23, no. 287 (June 19, 2002): 3,116-3,126.

Singh, Ram B. et al. “Effect of Antioxidant Rich Foods on Plasma Ascorbic Acid, Cardiac Enzyme and Lipid Peroxide Levels in Patients Hospitalized with Acute Myocardial Infarction,” Journal of the American Dietetic Association 95, no. 7 (July 1995): 775-780.

Dictionary

Antibiotics

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August 19, 2010 at 7:26 am

Chemicals that destroy or prevent growth of microorganisms including bacteria, molds, and fungi. Natural or synthetic compounds are used extensively as antibiotics to treat infectious diseases in animals and plants as well as in humans. Sulfanilamides, penicillins, and erythromycins are examples of major families of these drugs. Antibiotics impact human health in several ways. The prolonged use of broad-spectrum antibiotics in treating disease drastically alters the intestinal microflora by destroying beneficial bacteria. The loss of beneficial bacteria can permit less desirable, opportunistic microorganisms like yeast to flourish, cause intestinal inflammation, and decrease production of nutrients important in maintaining health of the colon. Antibiotics can affect specific vitamin requirements; chloramphenicol blocks riboflavin and vitamin B6 and B12, for example. Penicillin increases potassium requirements. Antibiotics can decrease nutrient absorption in general by altering the intestinal lining. Neomycin interferes with the uptake of fat, amino acids, carbohydrate, water-soluble and fat-soluble vitamins, calcium, iron, and vitamin K. Tetracycline decreases absorption of fat, amino acids, calcium, iron, magnesium, and zinc, while increasing the rate of urinary excretion of riboflavin, folic acid, and vitamin C.

Antibiotics can have a direct impact on the food supply. Half the antibiotics produced in the United States are applied to livestock. The benefits are more rapid growth and healthier animals. On the other hand the potential exists for generating drug-resistant pathogenic bacteria and persistent antibiotic residues in meat and dairy products. The application of antibiotics in animal husbandry and the permissible levels of antibiotic residues in animal products are regulated by the U.S. FDA. The following examples illustrate the dimensions of this food safety issue.

Chloramphenicol

This drug can cause anemia in humans due to damage to bone marrow. Though banned from use with food-producing animals, periodic spot inspections showed it was widely used in cattle and hogs in the 1980s. The degree to which chloramphenicol continues to contaminate meat through illegal application, and the degree to which such a contamination affects health, are unknown.

Penicillin

This common antibiotic is used to treat dairy herds, among others. The allowable penicillin level in milk is 0.01 units per milliliter (about 20 drops) of milk, but spot checks have found 10 times this level in commercial milk. Such high levels can cause allergic reactions in susceptible individuals.

Sulfamethazine

This sulfa drug is a widespread contaminant in meat, poultry, and milk. One-fourth of milk sampled in the late 1980s was contaminated, despite the U.S. FDA ban on this drug in milk. Sulfamethazine is suspected of being a carcinogen. (See also acidophilus; meat contaminants; pesticides.)

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Growing Your Own

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August 17, 2010 at 6:38 am

To bypass the dangers of incorrectly identifying herbs in the wild, and to get started using fresh herbs without a botany lesson, you always have the option to grow your own. You can start by visiting a nursery that grows herbs and purchasing your own seeds (rather than collecting seeds from the wild, which will again involve the problems with misidentifying).

The biggest benefit of growing your own herbs is that because you have purchased your seeds, you will be able to correctly identify the herb that grows. Most plants you grow at home will be mild because of the pampering you give them and will be safe to use for occasional medicinal purposes — they’ll be especially useful for spices and cooking.

If you look at your thumb and see that it is more orange, purple, blue, or anything but green, but you still desire to grow a few of your own herbs, then we should cover a couple of the basics here first. First of all, you might want to consider planting perennials instead of annuals; or, if you are patient, try biennials, which take two years to bear fruit or flowers.

Terms related to herbs or holistic health

Perennials are plants that have a life span of more than two years — if you are lucky, these plants come back over and over again for years. Annuals are plants that live and grow for only one year or season and then die. Biennials are plants that usually require two years to reach maturity; these bloom in the second year before dying.

You don’t need to be a country boy or girl to grow your own herbs; even city-dwellers can grow herbs in a windowsill flower box, or in small pots set by a window. Whether growing indoors or outdoors, take a look at the following table for 10 popular herbs to grow, with their category and some uses. This chart will help you if you are feeling stood up because you have been waiting patiently for your basil (an annual) to re-grow again, but it never shows! (Don’t take it personally — this is basil’s nature.)

Popular Herbs and Their Uses

Herb Latin Name Type Uses
Anise Pimpinella anisum Annual Taken by nursing mothers to produce lactation; seeds sooth stomach. Used as a spice (licorice-type flavor) and to flavor liquors. Leaves are used in salads.
Basil Ocimum basilicum Annual Used as a spice mainly to flavor tomato-based dishes, spaghetti sauces, and Italian dishes. The fresh plant is said to repel mosquitoes and flies.
Chamomile Matricaria recutita Annual Tea or capsules are used to calm nerves and settle the stomach. Used in shampoos for blond highlights. Great ingredient in eye pillows. Fresh plant is an insect repellent. Use in potpourri.
Catnip Nepeta Cataria Perennial Soothes stomach; moms find it helpful for colicky babies. Cat’s love to eat it, so keep it away from them when trying to grow it; the dried herb stuffed into a cat’s toys will serve as entertainment for you and your cat (it makes cats act intoxicated and silly!).
Chives Allium Schoenoprasum Perennial This herb from the onion family is popular as a topping on baked potatoes or any foods you would add onions to for flavoring. Folklore used hanging chives to chase away evil spirits.
Parsley Petroselinum crispum Biennial Aids digestion and urinary tract. Decorates food plates. Attracts a caterpillar that will turn into a black swallowtail butterfly—an endangered species!
Sage Salvia officinalis Perennial Used as a seasoning for meats. Used medicinally for sinuses, nerves, bowels, and the bladder.
Clary sage Salvia viridis Biennial Decorative with blue and white flowers. Attracts hummingbirds. Oil is used to balance hormones in women, and some use it as a perfume.
Thyme Thymus vulgaris Perennial Used as a spice. Medicinally has been used to boost the immune system. Many different types of thyme are available, some very decorative for growing; ask your nursery specialist.
Valerian Valeriana officinalis Perennial Used as a sedative. Grown for sweet fragrance, but the root (the medicinal part of the herb), is repulsive to humans, yet irresistible to cats! (Then again, most of us are not fond of mice either!)

Harvesting is tricky business because it will vary depending on where you live and what your climate is like. It will also depend on what use you will have for the herb you harvest and which herbs you are harvesting. For instance, the medicinal value of ginseng root is not effective until it is at least five years old. Some manufacturers will sell ginseng that is immature and therefore not very potent. Again, be sure you know or trust your source, especially when purchasing ginseng because this is one of the more expensive herbs.

About overcoming an ailment with herbs

When growing parsley indoors from a seed, the herb should not be exposed to sunlight until it sprouts from the dirt. To avoid unintended light, cover the pot lightly with some newspaper until you see it sprout

As a general rule, my herb-growing friends tell me that you should harvest your flowering culinary herbs (herbs you are using for spice and food additions) just before they flower to preserve the essential oils (which give them their strong flavor and smell) — unless, of course, you are growing the herbs for the use of their seeds, such as with fennel, anise, or dill.

After you learn when to harvest your herbs for your purposes, you will need to learn how to dry them. Again, this will vary depending on what type of herb you are harvesting and what you are going to use it for.

In general, you can bunch most of your herbs and place them in paper sacks. You should mark on the outside of the bag what the herb is so you don’t get them mixed up. Some herbs should be bunched and then hung upside down from a string, and still other herbs can be placed directly into vases as decorations and left to dry as a dried flower decoration.

About overcoming an ailment with herbs

Some pretty flowers that you can add to your herb bunches are very beautiful fresh or dried, but are not well known for any medicinal qualities; these include marigolds, pansies, roses, and bachelor buttons.

Herbal medicine | Tags:

An Herbal First Aid Kit

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August 15, 2010 at 12:56 pm

Are you a traveler? Do you like to go camping, hiking, backpacking, or any of the other fun outdoor sports that lead you away from your medicine cabinet or a family physician? Great! This chapter is for you.

In this post, you will learn how to make your own herbal first aid kit, and you’ll learn the multi-faceted uses of six popular herbs or herbal oils. You can take this kit along with you in a backpack or a suitcase when traveling. It will come in handy if you get yourself into trouble, and it can help tide you over in case you can’t reach a medical doctor right away. In fact, this kit can sometimes even negate the need for a doctor visit! Now, come along as we continue on the long path through herbalism.

Capsicum, Not Too Dumb to Keep on Hand

Encapsulated, dried herbs are especially useful to take as a first aid kit for hikers and backpackers because of their light weight. When stored in a compartmentalized container, herbs can be taken along just about anywhere.

At the end of this post, I’ll give you some suggestions about how and what to store all these different herbs in, but for now, let’s talk about how you can use each one in a pinch. Don’t hesitate to make up this kit to store in your medicine cabinet at home, either — it can come in handy almost anytime, anywhere. I am a traveler, and it has come in handy for my family, my friends, and me in many countries, hotel rooms, and backpacking trips.

About overcoming an ailment with herbs

You might want to make several small herbal first aid kits and store them in different places. For instance, make one for your boat, one for your home, one to keep with the camp gear, one for each vehicle, and one with your traveling bags.

Capsicum (Capsicum minimum, C. frutescens), also referred to as cayenne pepper or red pepper, is one of those herbal cure-all herbs and makes an excellent addition to any first aid kit. The fruit (pepper) of this plant is used for medicinal purposes, food, and spice. This herb is very hot, and if you buy it in encapsulated form, you will notice that it is red in color.

I would add a bottle of capsicum capsules to your first aid kit instead of a bulk powder. This herb is useful in winter if you are venturing on a snowmobile or a crosscountry skiing trip. The pepper powder is stimulating and brings blood supply to the area to which it is applied. In other words, if you are on a winter outing, take capsicum with you to keep you warm. Simply open a capsule and sprinkle some in your socks and mittens to help prevent frostbite and keep your extremities warm. In addition, you can swallow a couple of capsules internally, and you will be able to feel the inner fire that it ignites.

Capsicum is also useful in your first aid kit as an emergency fix to stop bleeding. Capsicum is so “hot” that it has an ability to actually cauterize a wound in some cases. If you cut yourself and wish to stop the bleeding, empty a capsicum capsule onto your cut. The application will sting, but it should stop your bleeding right away.

Capsicum seems to have an ability to deaden the nerve endings temporarily, which is why it has been used as a pain-relieving remedy. While it may deaden pain, it also brings blood to the area to which it is applied and therefore can enhance your healing. Blood circulation brings nutrients and oxygen and is imperative to the process of tissue healing; capsicum can aid this process.

Warnings about the use of herbs

The only caution with using capsicum in a lotion or gel is to watch out that you don’t touch your eyes or any other sensitive parts after using the formula. If you do, flush out the area with cool water immediately. If you are sensitive to hot foods, try capsicum in very small doses.

For a sore throat, gargle with capsicum added to water or juice. Although it may burn at first, the pain should subside within a short time, and your throat will feel better. You can even make capsicum into a spray for sore throats. (See the post “Tonsillitis: Tea Tree for Two, and Two for Tea Tree” for an herbal throat spray containing capsicum.)

When camping, you can sprinkle capsicum on foods — especially bland-tasting backpacking foods (although some companies are offering much better tasting foods these days). When taken internally, capsicum can increase the production of digestive acid and also may help expel gas from the intestines, relieving gas pains.

Herb Lore: information related to holistic health

If you are a comic fan, check out the back to see ads offering all types of gag gifts. You might see an ad for a type of gum that, as a trick, you offer to your enemies. When I was a young teen, I remember the ad showing a cartoon face of a man who had obviously chewed the gum and whose face was red as a beet. The drawing shows him perspiring heavily with his tongue sticking out and his hand grasped around his neck in choking agony! Guess what the main ingredient added to the gum was to cause this effect? You guessed it: good old capsicum!

The herb powder can be added to lotion or gel and can be applied to areas that need pain relief or circulation. The active ingredient capsaicin is a popular extract added to many pain-reliving formulas.

Capsicum is so stimulating, in fact, that it can be used in cases of severe shock, fainting, or even heart attack to bring someone back to consciousness. Add a small amount of powder to the tip of the tongue in these cases to try to stimulate blood flow back to the head and help the person recover from shock.

Giving aspirin to a heart attack victim has been publicized lately, probably due to the fact that aspirin thins the blood. Heart attacks that involve a blockage of blood flow to the heart can be helped by thinning the blood to allow at least some passage of blood to the heart. But don’t forget about white willow bark, which is where the active ingredients in aspirin originally came from. White willow can be just as effective. Capsicum also is a circulatory stimulant, and both of these can work together to save a life in an emergency situation.

To sum up, here are some of the ways capsicum has been used and why it can be an integral part of any first aid kit.

Capsicum has been used to:

  • Stop bleeding
  • Relieve pain
  • Warm extremities
  • Increase internal heat
  • Add flavor to foods
  • Increase circulation
  • Aid digestion and expel gas from intestines
  • Stop heart attacks
  • Bring people out of shock or keep them from going into shock after trauma

Take some along in capsules instead of the bulk form in case you need to swallow some.

Activated Charcoal, for De-Activating Poisons

Although charcoal is not an herb, It should be added to a first aid kit as a potent remedy to counteract the affects of poisoning.

When camping, traveling, or otherwise eating things that may not be clean, there is always the threat of food poisoning.

However, you are more vulnerable to poisoning from snake bites, spider bites, and insect bites and stings when you are camping or out in the wild. This is where charcoal could serve to save your life.

Activated charcoal has properties that can attract (like a magnet) poisonous substances from your body, making them unable to be absorbed or can at least render them less harmful to the body. If a snake, scorpion, tick, spider, or any other animal or insect bites you — or even if you think you were bitten — you can begin taking a few capsules of charcoal to counteract any possible toxic side effects.

You can also make a poultice out of charcoal and apply it directly to a bite to draw out the poisons through the skin.

If you suddenly have an attack of diarrhea, you might want to consider taking a few capsules of charcoal as well. Diarrhea usually indicates that the intestines are reacting to some type of poison that the body is trying to rid itself of rapidly. Activated charcoal will assist the body in getting rid of the toxin and will help you to recover while you are seeking the medical attention you may need.

About overcoming an ailment with herbs

Another good remedy that you might want to take with you is blackberry tea. If you pack tea bags, make sure you put them in a sealed plastic bag or wax paper to preserve freshness. This tea makes a strong astringent herbal remedy, and I have seen it stop chronic cases of unexplained diarrhea right away.

Clove Oil, Not a Snake Oil Remedy

We talked a lot about cloves and its properties back in the post “A Toothful Solution”. Unexpected toothaches are one of the reasons you may benefit from having a small bottle of clove oil in your herbal kit.

Clove oil has an analgesic (pain-relieving) effect on tissues, and a small amount applied topically on or around sore gums or to an aching tooth can relive pain until you can get to see your dentist. Clove oil may also be used to apply topically if you have broken a tooth, to help numb the pain of an exposed nerve.

I can’t vouch for this, but it is said that chewing on two raw cloves without swallowing also will curb someone of an alcohol craving. The strong taste of cloves left in your mouth will probably curb your appetite for almost anything, at least temporarily.

Besides its topical pain-relieving virtues, clove oil is a bug repellent, which is especially appealing to campers and hikers. A small amount can be applied to your hat or garments where bugs are bugging you!

Cloves can be used to kill bacteria, and therefore are used as an antiseptic for washing hands before preparing food when camping. This herb also has been used to ease indigestion, laryngitis, nausea, toothaches, vomiting, flatulence, abdominal pain, and asthma.

Cloves are a powerful remedy against parasites and can help you expel worms if you suspect you have picked up a parasite. You can add a tiny drop of clove oil to a liquid and then drink it; this is usually more than enough to expel a parasite. In general though, cloves are not recommended for internal use at all because of their strong and sometimes irritating effect on the body.

Children should not use the herb, although you can wet your finger and then add a drop of clove oil to apply to babies’ gums when they are teething to ease their pain.

About overcoming an ailment with herbs

If you make a mixture of clove oil and peanut oil or another type of non-essential oil that doesn’t evaporate so easily, like olive oil, it will help keep the essential oil from quickly evaporating when you apply ft to cloth for repelling insects.

Arnica You Glad You Use Herbs?

The yellow flowering herb arnica (Arnica montana) can be purchased as a topical application or for internal use as a homeopathic remedy. Arnica can be poisonous, so take internally only in a homeopathic solution as directed on the label. Never ingest arnica from the wild.

Terms related to herbs or holistic health

A homeopathic is a highly diluted solution made from plant, animal, or mineral extracts. The dilution renders the solution non-toxic to humans, and the dilution also makes it more effective as a medicine.

A homeopathic rule of thumb is that less is best. In other words, taking larger quantities is less effective than taking smaller amounts more often. I always have some arnica on hand to use for any type of trauma, stress, shock, bumps, bruises, emotional distress, and muscle soreness. Arnica is a wonder remedy, as far as I’m concerned, and should be a part of everyone’s first aid kit. My first introduction to the herb came when a family member, Sherry, came to my rescue at night, after I was accidentally smashed in the nose with great force. I heard the crunch of my cartilage and feared to look at my reflection, thinking I had been disfigured for life! Sherry was a self-taught natural herbalist and healer. I think her Cherokee blood and her close involvement in her tribe’s traditional ceremonies gave her a special talent for knowing exactly what remedy to use for what ailments. She helped me learn a lot about plants, but I had no idea about arnica until that night.

By the time she could get to me, my crying from the initial pain and shock had begun to subside, and I dared to look in the mirror. I thought my nose was broken, and two dark blue half-circles had begun to appear under my eyes. When Sherry arrived, she had me hold out my hand, and she rolled six tiny white pills into my hand. She told me to put them under my tongue and let them dissolve. I did, and I immediately felt calmer, although I wasn’t sure if it was Sherry’s presence or the arnica that made me feel better. My prescription from Sherry was to take six of these little pills every two hours for the rest of the night, and then four pills every four to six hours for the next day. I followed her suggestions faithfully.

When I woke up the next morning, I was stunned to see that the dark purple coloring that was beginning to form under my eyes had faded into a pale blue. In two days, the discoloring was completely gone! I then understood the value of arnica: It not only can help calm you down from emotional or physical trauma or shock, but it also had an almost miraculous ability to heal and prevent bruising.

Another story about arnica stems from a time when another family member of mine had to undergo some serious facial surgery. She had to be bandaged for weeks afterward, and the bandages were to be changed weekly. I was just beginning to become more learned in the use of herbal remedies, and I suggested that she take arnica.

She took the arnica several times a day, three days before her surgery, and then continued on more frequent but smaller doses after her surgery. The first week after surgery, she went in for her check-up. After her bandages were removed, she reported that her surgeon was in absolute amazement at how well she had healed! The surgeon questioned her about what she had done specifically so that he could recommend this miracle-healing agent to his future patients.

For your herbal first aid kit, I suggest that you purchase arnica homeopathic in a pill form because pills are easier to pack than a liquid. You can also obtain a jar of cream to apply to sore areas after hiking, or to put on bumps and bruises of any kind. If you can get arnica in a liquid homeopathic with a glass dropper, this is also a sufficient way to take the remedy, but it might not be as convenient for packing.

Warnings about the use of herbs

Arnica also works well when applied as an ointment or cream. However, the cream should never be applied to any open wounds or cuts because ft may cause a bacterial infection. Only apply to areas that are bruised or sore.

Ephedra, Help from China

Chinese ephedra, also commonly called ma huang, is a heart stimulant that increases circulation and opens bronchial passages. This makes it an excellent emergency remedy for anyone who is prone to asthma. Before I was on my daily herbal routine, I suffered from asthma and allergies (among many other ailments). For me, taking one or two capsules of herbs containing ephedra was equivalent to taking a shot off my bronchial inhaler. Ephedra stops bronchial constriction and eased my breathing and chest tightness within 15 minutes. If someone begins to get short of breath and has a tendency toward asthma, this remedy can be taken in small doses as a preventative remedy. It can be used in slightly larger doses if asthma strikes.

Read up on ephedra in the post “Asthma: It’s So Wheezy to Fix.” You will see that it is banned in some states and is not suitable for everyone, but this herb has been a godsend for many who used to suffer from asthma.

Ephedra can also be used as part of a weight-loss program because it curbs the craving for sweets, gives energy, and lessens appetite. Taking a capsule or two can ease a craving for camping junk food, too! What? No s’mores?

Warnings about the use of herbs

Because ephedra is a heart stimulant, those with high blood pressure or other heart problems should avoid using it. This herb is also not recommended to be used daily for more than two weeks in a row, nor should it be used by pregnant or nursing moms.

Ephedra also helps many with allergies, which could come in handy when hiking and camping. Plane travel, where you have the pleasure of breathing circulated air used by all passengers, seems to create more sniffles and sneezes as well, and ephedra can prove beneficial here, too. Just be sure to take it in small quantities, such as one capsule at a time, and see how you feel. You will usually find ephedra mixed in with other herbs to lessen the impact of the speedy feeling you can get from it.

If you live in a state or country where ephedra is not allowed, you can substitute lobelia in your herbal first aid kit in its place. Lobelia can also be used for allergies, asthma, and coughs. In higher doses, you can use lobelia as an emetic (induces vomiting), which can come in handy in case of poisonings.

Peppermint for an Uplifting Time

One of my favorite herbs and essential oils of all time is peppermint (Mentha piperita). This cooling, minty, refreshing essential oil can make a nice addition to your first aid kit for many types of uses.

First of all, peppermint is stimulating, so it can be used as a pick-me-up by rubbing a little dab onto the temples. Just be careful not to touch your eyes after touching peppermint oil. You can put a dab on the middle of your tongue, close your mouth, and inhale. The “fumes” go directly to your brain area and help keep you alert and “mintally” stimulated.

Here’s a list of the variety of ways peppermint can come in handy:

  • Peppermint has been used topically to alleviate migraines and headaches.
  • It can be rubbed onto a sore gum to ease toothache pain.
  • Peppermint is great for camping breath, because a little dab can refresh your entire mouth.
  • Some say that peppermint oil works great as a mosquito repellent, too.
  • On a hot day, a few drops can be added to a tiny spray bottle filled with water and sprayed onto the skin for a stimulating cooling effect.
  • For stomach aches, heartburn, and indigestion symptoms, a dab of the oil on the tongue can make you feel better.
  • For fevers, a few drops can be added to a wet washcloth and applied to the forehead.

About overcoming an ailment with herbs

Peppermint oil is also a great remedy to have on hand to stimulate blood circulation to an area. Some folks add it to their shampoos to bring circulation to the head and believe ft helps stimulate hair growth.

Now that you know what you want in your herbal first aid kit and understand the uses of each herb, you need to know where and how to conveniently put it together.

I have a couple of hints for you to make your own, although I am sure you can find some commercially packaged kits out there. If you do, you can replace whatever herbs you don’t like with the ones listed here, or you can add your own favorites.

About overcoming an ailment with herbs

Everyone should be certified in basic CPR training because it can save your life or others. CPR training is offered many places and is inexpensive and sometimes free if taken through your employer. Call your local hospital, community education center, or college, or ask your employer about getting trained in this life-saving method.

My favorite way to carry herbs for travel is in plastic Tupperware-type containers with adjustable trays to hold loose capsules. These vitamin chests can be found in most health food stores and come with stickers so you can label your compartments accordingly. The containers also are sturdy and travel well.

You will need to purchase a container that has at least six compartments if you are going to take the six herbs we talked about in this chapter. Or, you can purchase one with more compartments, and add your other first aid supplies such as bandages, sterile gauze, a sewing kit, aspirin (or white willow bark capsules), and the like. I like the hard containers because they keep the herbs from getting crushed, but if you are careful, you might find that a material case (such as a jewelry or make-up-type case made from a lightweight material) might be an easier way to carry your kit for camping.

Your Herbal First Aid Kit

Herb External Uses Internal Uses
Capsicum Sprinkled in socks or mittens will warm hands or feet; can help stop bleeding Used to flavor bland tasting backpacking food
Activated charcoal Poultice applied to bites or stings Poisonings
Clove oil Toothaches, insect repellent Parasite expeller (minute doses only)
Arnica Muscle soreness, bruises, blood blisters Bruising, muscle soreness, pain, shock, emotional and/or physical trauma
Blackberry tea bags Help shrink tissues (astringent) Can help stop diarrhea
Ephedra (ma huang) None Aids asthma and allergy attacks
Peppermint oil Mental pick-me-up; good for migraines, headaches, nausea, stomach ache; cooling Numbs toothaches, alleviates canker sore pain and headaches; mental stimulant; freshens breath; helps get rid of fever
Herbs: Uses, Side effects | Tags: ,

Saw Palmetto

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August 12, 2010 at 7:39 am
Synonyms: Brahea serrulata; Sabal serrulata; Serenoa repens; Serenoa serrulatum; Šliaužiančiųjų serenojų vaisiai (saw palmetto fruit); American Dwarf Palm; PA-109; Palmera de Florida; Sågpalmettofrukt (saw palmetto fruit); Sabal; Sabalis Serrulatae; Sahapalmunhedelmä (saw palmetto fruit); Serenový plod (saw palmetto fruit)
ATC code: G04CX02

Pharmacopoeias. In Europe and US. US also includes the extract and the powdered form.

European Pharmacopoeia, 6th ed. (Saw Palmetto Fruit). The dried, ripe fruit of Serenoa repens (Sabal serrulata). It contains not less than 11.0% of total fatty acids, calculated with reference to the dried drug. Protect from light.

The United States Pharmacopeia 31, 2008 (Saw Palmetto). The partially dried, ripe fruit of Serenoa repens (Arecaceae). Store in airtight containers. Protect from light.

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Saw palmetto is the dried fruit of the American dwarf palm tree, Serenoa repens (Arecaceae). It contains various steroidal compounds with anti-androgenic and oestrogenic activities, one of which is sitosterol. Saw palmetto is used for the treatment of benign prostatic hyperplasia. Preparations of alcoholic or lipophilic extracts have typically been given in oral doses of 160 mg twice daily, or 320 mg once daily.

Adverse effects. EFFECTS ON THE LIVER. Cholestatic hepatitis occurred in a man who took a herbal preparation containing saw palmetto for 2 weeks to treat nocturia and hesitancy.

Uses. BENIGN PROSTATIC HYPERPLASIA. A lipid hexane extract of saw palmetto has been shown to be generally superior to placebo, and of similar efficacy to fmasteride in the treatment of benign prostatic hyperplasia. A systematic review of randomised studies of various saw palmetto extracts concluded that they improve urological symptoms and flow measures. However, a more recent double-blind study concluded that treatment for one year was not superior to placebo for improving urinary symptoms and objective measures.

Preparations

The United States Pharmacopeia 31, 2008: Saw Palmetto Capsules.

Proprietary Preparations

Argentina: Beltrax Uno Herbaccion Prostatico † Permicaps Permixon Sereprostat- †

Australia:: Bioglan Pro-Guard Prosta †

Austria: Permixon Prosta-Urgenin

Belgium: Prosta-Urgenin Prostaserene

Brazil: Permixon Prostalium † Prostat Prostatal Renopen

Chile: Prostatort

Czech Republic: Capistan Prosta-Urgenin Prostakan Mono Prostamol Uno Spalda Sabal

France: Permixon

Germany: AzuprostatSabal † Eviprostat-S Hyperprost Uno Normurol † Planturol-P Prosta Urgenin Uno Prostagutt mono Prostagutt uno Prostaplant † Prostess Remiprostan uno Sabacur uno Sabal Sabal uno Sabalvit Sabonal Uno Sita Steiprostat Strogen Talso

Greece: Libeprosta Urisedon

Hungary: Prostakan Prostamol Uno Saballo Strogen Uno

Indonesia: Lanaprost Prostakur

Israel: Permixon

Italy: Biosernl Permixon Prosteren Rilaprost Saba Serpens

Mexico: Permixon Prostasan Prostex Urogut

Poland: Bioprost Fitoprost Permixon Prostamol Uno Prostaplant Sterko

Portugal: Permixon Prostiva † Sereprosta

Russia: Permixon Prostamol Uno Prostaplant

Singapore: Permixon

Spain: Permixon Sereprostat

Switzerland: Permixon Prosta-Urgenine ProstaMed Prostasan SabCaps

Thailand: Permixon Urogutt

UK: Prostasan Sabalin

Venezuela: Permixon

Multi-ingredient

Argentina: Anastim con RTH Argeal Catiz Plus Keracnyl Normoprost Plus PR21 Sabal Ultracal

Australia:: Bioglan Mens Super Soy/Clover Extralife Flow-Care Lifechange Mens Complex with Saw Palmetto † Serenoa Complex Urapro Urgenin † Urinase †

Austria: Prostagutt Spasmo-Urgenin Urgenin

Belgium: Urgenin

Canada: Damiana-Sarsaparilla Formulaf Prostate Ease Prostease ProstGard

Czech Republic: Prostakan Forte

France: Argeal Kelual DS Keracnyl Sabal

Germany: Cefasabal Granu Fink Prosta Nephroselect M Prostagutt forte

Hong Kong: Palmetto Plus Phyto-Ease Prostease Sawmetto Vivo-Livo Urgenin

Indonesia: Instink Maxirex Menolia Reximax Soprost

Israel: Urgenin

Italy: Biothymus M Urto Pluvio Prostaplant

Malaysia: Prostakan Total Man

Mexico: Prosgutt

Poland: Naturapia Prostata Penigra

Portugal: Efluvium Anti-caspa Efluvium Anti-seborreico Neo Urgenin Spasmo-Urgenin

Russia: Prostagutt Forte

South Africa: Spasmo-Urgenin

Singapore: Palmetto Plus

Spain: Neo Urgenin Spasmo-Urgenin Urgenin

Switzerland: Granu Fink Prosta Phytomed Prosta † Prosta-Caps Chassot N1 Prostagutt †

Thailand: Spasmo-Urgenin

UK: Antiglan Daily Fatigue Relief Damianaand Kola Tablets Elixir Damiana and Saw Palmetto Regina Royal Concorde Strength

Venezuela: Sabal

Herbs: Uses, Side effects | Tags: ,

Feverfew

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August 10, 2010 at 5:35 am

Drug Nomenclature

Synonyms: Őszi margitvirág; Camomille (Grande); Matricaria; Mattram; Nať kopretiny řimbaby; Reunuspäivänkakkara; Tanaceti Parthenii Herba; Vaistinių skaistenių žolė

Pharmacopoeias. In Europe and in US. US also describes Powdered Feverfew.

European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Feverfew). The dried, whole or fragmented aerial parts of Tanacetum parthenium. It contains not less than 0.2% of parthenolide (C15H20O3 =248.3), calculated with reference to the dried drug. It has a camphoraceous odour. Protect from light

The United States Pharmacopeia 31, 2008, and Supplements 1 and 2 (Feverfew). It consists of the dried leaves of Tanacetum parthenium (Asteraceae), collected when the plant is in flower. Store in a dry place. Protect from light.

Adverse Effects and Precautions

Mouth ulceration and soreness have been reported following ingestion of feverfew, and may be due to sensitisation; if they occur feverfew should be withdrawn. Contact dermatitis has been reported. Feverfew is reputed to have abortifacient properties and it is suggested that preparations should not be used in pregnancy.

Effects on the blood. There have been suggestions that feverfew may increase the risk of bleeding during surgery or in patients taking anticoagulants. However, although inhibition of platelet aggregation has been reported in vitro or in animals a review of clinical studies noted that feverfew did not appear to affect haematological safety parameters.

Interactions

It has been suggested that feverfew may enhance the effects of anticoagulants (but see Effects on the Blood, above).

Uses and Administration

Feverfew consists of the dried leaves of the plant Tanacetum parthenium (Asteraceae). It is a traditional herbal remedy used in the prophylaxis of migraine. Its effects have been attributed to the plant’s content of sesquiterpene lactones, notably parthenolide. A preparation of the dried leaf powder, which has been standardised to provide a minimum of 0.2% parthenolide, is available in some countries. A suggested oral dose is 250 mg daily; a lower dose of 100 mg daily has also been given..

Migraine. Feverfew is a traditional herbal remedy used in the prophylaxis of migraine. Studies of standardised preparations of the freeze-dried powdered leaf have produced variable results in preventing or ameliorating migraine attacks, and systematic reviews suggest that its effectiveness in preventing migraine remains to be established.

Rheumatoid arthritis. Feverfew has been used as a herbal medicine for the treatment of arthritis but although it has anti-inflammatory activity in vitro, a clinical trial found it to be ineffective in rheumatoid arthritis.

Preparations

Single-ingredient Preparations

Australia: Herbal Headache Relief; Brazil: Tanaceto; Tenliv; Canada: Tanacet; Switzerland: Partenelle; United Kingdom: Tanacet

Multi-ingredient Preparations

Australia: Albizia Complex; Extralife Arthri-Care; Extralife Migrai-Care; Guaiacum Complex; Germany: Presselin Stoffwechseltee

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