A Review of Plants Used in
the Treatment of Liver Disease: Part 2

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:    Frankp@chiro.org

FROM:   Alternative Medicine Review 1999 (Jun); 4 (3): 178–189 ~ FULL TEXT

Scott Luper, N.D.

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Botanical medicines have been used traditionally by herbalists and indigenous healers worldwide for the prevention and treatment of liver disease. Clinical research in this century has confirmed the efficacy of several plants in the treatment of liver disease, while basic scientific research has uncovered the mechanisms by which some plants provide their therapeutic effects. This article is Part Two in a review of botanicals used in the treatment of liver disease. Curcuma longa (turmeric), Camellia sinensis (green tea), and Glycyrrhiza glabra (licorice) are reviewed in this installment. Silybum marianum (milk thistle) and Picrorhiza kurroa (kutkin) were reviewed in Part One. (Altern Med Rev 1999;   4 (3):   178-189)\

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Introduction

Treatment options for common liver diseases such as cirrhosis, fatty liver, and chronic hepatitis are problematic. The effectiveness of treatments such as interferon, colchicine, penicillamine, and corticosteroids are inconsistent at best, and the incidence of side-effects profound. All too often the treatment is worse than the disease. Conservative physicians often use a "wait and see approach" for many of their patients, waiting for the time when the disease has progressed to the point to warrant the use of heroic measures. Physicians and patients are in need of effective therapeutic agents with a low incidence of side effects. Several botanical medicines potentially constitute such a group.

In recent years, researchers have examined the effects of plants used traditionally by indigenous healers and herbalists to support liver function and treat diseases of the liver. In most cases, research has borne out the traditional experience and wisdom by discovering the mechanisms and modes of action of these plants, as well as confirming the therapeutic effectiveness of certain plants or plant extracts in clinical studies.

Several hundred plants have been examined for use in a wide variety of liver disorders. Only a handful have been fairly well researched. These plants include Silybum marianum (milk thistle), Picrorhiza kurroa (kutkin), Curcuma longa (turmeric), Camellia sinensis (green tea), and Glycyrrhiza glabra (licorice). Silybum marianum and Picrorhiza kurroa were reviewed in Part One. Curcuma longa, Camellia sinensis, and Glycyrrhiza glabra are reviewed in this article.

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Green Tea (Camellia sinensis)

Description: Green, black, and oolong teas all derive from of the leaves of Camellia sinensis, which is cultivated widely in China, India, Japan, and Indonesia. When cultivated, it grows as a well-trimmed bush with alternating evergreen leaves. Originally from East Asia, the wild plant grows as a large shrub or tree. Green tea is made from unfermented leaves which are lightly steamed to inactivate the enzymes which would allow fermentation, then dried. The leaves of oolong tea are partially fermented, and black tea is fully fermented. The greater the fermentation, the lower the polyphenol content and the higher the caffeine content. Black tea has 2-3 times the caffeine content of green tea. [26]

History and Folk Use: Tea has been used as both a drink and a medicine for approximately 5000 years in China. Historical uses of tea are as a stimulant, an astringent for clearing phlegm, and as a digestive aid. [27]

Active Constituents: Tea contains a wide assortment of bioactive constituents, most of which are contained in two groups, alkaloids and polyphenols. Examples of alkaloids found in tea include caffeine, theobromine, and theophylline. [28] These alkaloids provide the stimulant effects of tea and figure prominently in the experience of tea drinking, although they are not thought to be central to tea's medicinal effects.

The polyphenols found in all tea give it its astringent, somewhat bitter flavor. The hepatoprotective and other health effects of green tea are believed to be chiefly dependent on the polyphenol content. [29–31] The polyphenols contained in teas are classified as catechins, which are considered to be bioflavonoids, which in turn is a subcategory of the larger group of polyphenols. [28] Green tea contains six primary catechin compounds: (+)-catechin, gallocatechin, epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate. Epigallocatechin gallate (also known as EGCG) is considered to be the most active component, and is the best researched of the green tea polyphenols (GTP). [30, 32]

Green tea contains about 30-40 percent polyphenols (dry weight), whereas the polyphenol content of black tea is 3-10 percent. The average cup of green tea contains 50 to 150 mg of polyphenols. [28]

Pharmacokinetics: The bioactive constituents of green tea are absorbed following oral administration in a dose dependent manner. The catechins are metabolized by the liver and kidneys, and cleared from the body chiefly by the kidneys. The plasma half-life of epigallocatechin gallate is 5.5 hours. [26, 33] Based on the author's clinical experience, a typical recommended dose of green tea solids with polyphenols standardized to 50 percent is from 100 to 300 mg three times daily.

Hepatoprotective Activity: Green tea has been found to provide protection to the liver against a variety of toxic insults, including the industrial solvent 2-nitropropane (also found in cigarette smoke), [34] alcohol, [35] d-galactosamine, [36] and 1,4-naphthoquinone. [31] In addition, the anti-carcinogenic effect of green tea on the liver and other organs has been well researched. [32, 34, 37, 38]

Much is known about the hepatoprotection afforded by green tea. Catechins have been discovered to be powerful antioxidants, which is though to be at least in part responsible for green tea's hepatopro-tective activity. In 2-nitropropane poisoning, epigallocatechin gallate administration lowered hepatic lipid peroxide levels 100 percent at six hours and 30 percent at 15 hours. Histopathological examination revealed effective protection against induction of hepatic degenerative changes by 2-nitropropane at 15 hours.37 Catechins have also been shown to inhibit lipid peroxidation due to other toxins, including tert-butyl hydroperoxide and bromotrichloromethane, [29] 1,4-naphthoquinone, [31] and singlet oxygen. [39]

The hepatoprotective effect of green tea is not dependent on its direct antioxidant effects alone. Green tea catechins have been shown to maintain intracellular protein thiol levels. [31] Protein thiols help maintain the intra-cellular reduction-oxidation (redox) balance. Protein tertiary configuration (shape), and therefore cellular function, is dependent on the maintenance of the redox balance. In rat liver cells exposed to 1,4-naphthoquinone, green tea extract prevented the expected cellular damage. This protective effect was suggested to be due to maintenance of protein thiol levels by green tea. [31]

Detoxification Activity: Glucuroni-dation, the predominant human Phase II liver detoxification pathway, has been shown to be enhanced with green tea administration. [40, 41] Glucuronic acid is conjugated with toxins to facilitate their elimination from the body via the bile. Examples of toxins eliminated in this manner include aflatoxin and acetaminophen metabolites. Green tea administration in rats (as their only drinking fluid) increased glucuronidation by 100 percent. The authors of the study suggest the increase in glucuronidation may contribute to the anti-carcinogenic effect of green tea by facilitating the metabolism of chemical carcinogens into inactive, readily-excretable products. [40]

The effect of green tea on other detoxifying and antioxidant enzymes is controversial. Some researchers found oral feeding of green tea in drinking water (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in the liver. [38]

Other researchers reported no increase in glutathione peroxidase, catalase, or superoxide dismutase following a much larger exposure of rats to green tea in drinking water (2.5%, w/v, as the sole drinking fluid, for four weeks). [40]

Green Tea and Hepatitis: One of the polyphenols present in green tea, (+)-catechin, has been studied for its effects on animal models of hepatitis, as well as in human clinical studies. Pure (+)-catechin (also known as (+)-cyanidanol-3 ­ trade name Catergen) has been used to treat hepatitis since 1976. [42] This compound has been shown to be an efficient immune stimulator, promoting activation of macrophages, cytotoxic-T-lymphocytes, and natural killer cells in mice in a dose-dependent manner. [42]

Several clinical studies demonstrate the effectiveness of (+)-catechin in the treatment of viral hepatitis. One double-blind study found a significant drop in antibodies to hepatitis B e antigen (HBeAg) in patients with HBeAg positive hepatitis B. Patients were given 1.5 g for two weeks, followed by 2.25 g for 14 weeks. HBeAg antibody titers decreased at least 50 percent in 31 percent of patients, (P < 0.01), and HBeAg completely disappeared in approximately 11 percent (P < 0.05). The patient group responding best to the treatment had higher initial values of SGPT, SGOT and gamma-globulin than the patients whose HBeAg titers remained unchanged. Mean values for these liver enzymes also fell significantly in the treatment group. The compound was reported to be well tolerated in this study, the only notable side-effect being a transient febrile reaction in 13 patients. [43]

In another double-blind study, 12 patients with chronic hepatitis B were treated with the combination of recombinant human alpha-interferon and (+)-catechin Ñ three million units of interferon twice per week and 2.5 g of (+)-catechin daily for 24 weeks. Four patients experienced clinical improvement in which HBeAg and DNA polymerase disappeared from sera, and aminotransferase activities fell to normal levels. Side-effects were minimal, and all patients tolerated the treatment. [44]

Pure (+)-catechin has been found to cause hemolysis in some patients, [45, 46] possibly by the promotion of antibody formation against (+)-catechin, which might cross-react with red blood cells. [47] However, there are no reports in the literature of green tea, green tea extracts, or green tea polyphenols causing this side-effect.

In an animal model of viral hepatitis, pre-treatment with green tea extract significantly prevented increases in hepatic transaminases and alkaline phosphatase levels in a dose-related manner. [48] With this information, as well as the research on (+)-catechin, one might surmise that green tea could be used as part of a hepatitis treatment protocol, although more human research is needed in this area before a solid recommendation can be made.

Green Tea and Liver Cancer: Much of the green tea research involves its effects on cancer prevention and treatment. A full review of the anti-cancer properties of green tea is beyond the scope of this review, but at least a passing mention must be made on the subject with regard to liver cancer.

Green tea has been found to reduce or prevent the growth of hepatic neoplasms in rodents. One study used mice which had been exposed to the known carcinogen diethylnitro-samine (DENA) (50 micrograms/kg bw, i.p., once per week for eight weeks). The mice were treated with green (and black) tea for 40 weeks. After treatment, the mice were examined for pulmonary and hepatic tumors. Mice treated with both DENA and tea displayed a significant decrease in the mean number of lung and liver tumors, compared to DENA-only treated animals. Mice receiving 0.63 or 1.25 percent green tea, or 1.25 percent black tea, exhibited a reduction in the incidence of liver tumors of 54, 50, and 63 percent, respectively, compared to DENA-only treated mice. [32]

Other researchers found similar results in rats, [49, 50] although one research group found a slight, but significant increase in the number of liver tumors in rats treated with green tea catechins and a decrease in intestinal cancer in the same animals. [51]

Toxicity: Green tea has not been found to be toxic at any dose. Animal studies (and the experience of a billion tea drinkers) have found no toxicity. [29] Single doses of decaffeinated green tea solids up to 4.5 g/day (equal to 45 cups of tea) have been well tolerated by humans. [34]

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