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Glycyrrhiza: Licorice as a liver herb

by Paul Bergner

Medical Herbalism 04-30-94 6(1): 6-7

Licorice root (Glycyrrhiza glabra) is a time-honored herbal medicine in the major world herbal traditions. It is used as a primary herb in perhaps more categories than any other medicinal plant. It is used with success for acute respiratory problems, gastric ulcers, gastritis, inflammatory conditions in general, and adrenal exhaustion. Components of licorice root have both estrogenic and anti-estrogenic activity (Leung; Kraus; Kumagai et al; Sharaf and Goma; Tamaya et al). It is thus an important herb for treating hormone-related female problems.

It has not traditionally been used as a liver herb, but medical research over the past two decades in Japan and China has shown that licorice is also an important liver herb with strong hepatoprotectant properties. This should not be thought of as just another minor use for licorice. It is as significant a hepatoprotectant as the better-known milk thistle seed, and acts through separate mechanisms than that herb. The two together should be considered in any hepatoprotectant formula or treatment plan.

Form and dose

Most of the Asian clinical research and practice has been with glycyrrhizin, a major constituent of licorice root. The product in most Japanese trials is Strong Neominophagen-C (SNMC) which contains glycyrrhizin (40 mg), and the amino acids cysteine (20 mg), and glycine (400 mg) in 20 ml saline solution. A typical treatment for hepatitis is 40 ml of SNMC a day for thirty days delivering 80 mg of glycyrrhizin per day (Hikino). The upper range of clinical trials has been 200 ml SNMC (400 mg glycyrrhizin) (Mori et al, 1989,1990), but trials above 100 ml (200 mg glycyrrhizin) have been rare, due to concern over possible side effects (see below) (Hikino).

Oral extracts

Comparable therapeutic levels of glycyrrhizin can probably be reached with oral preparations. Glycyrrhizin is considered the most important active constituent of licorice, and therapeutic levels for a wide variety of conditions are easily achieved with oral administration. Licorice root (G. glabra) contains 6-14% glycyrrhizin (Merck), so an oral dose of 7-8 grams powdered licorice would deliver the highest range of glycyrrhizin used in the hepatitis trials to the gut. This compares to a traditional Chinese oral dose of 3-12 grams G. uralensis (Bensky). How much of this would reach the plasma, and thus be equivalent to the intravenous trials, has not been tested. Oral administration of glycyrrhizin alone or as licorice root extract has been tested in mice (Ozaki et al), and found to be comparable, with each form achieving similar levels of glycyrrhizin or its active metabolites in the plasma.

Hepatitis

Clinical trials for hepatitis, especially chronic active hepatitis, have been so successful in Japan that glycyrrhizin is now a standard medical treatment there (Kumada et al; Matsunami et al.; Ohta et al; Su et al; Suzuki et al; Wang; Zhang et al).

Mechanisms of hepatoprotection

The mechanisms of hepatoprotection are diverse. They include antioxidant activity (Kiso et al; Abdugafurova et al; Tan; Ju et al), direct antiviral effects (Hikino; Crance), enhancement of interferon production (Hikino; Shinada) enhanced antibody production (Hikino), enhancement of extrathymic T-Cell activity in the liver (Kimura et al), and protection from immunological (auto-immune) injuries (Hikino; Mizoguchi et al). A number of animal and in vitro trials have shown that glycyrrhizin can protect liver cells from damage from a variety of chemical or immunological agents (Nakamura et al; Mizoguchi et al; Shibayama; Shiki et al; Zhao et al).

Other Clinical trials

Glycyrrhizin has also been effective in treating HIV/ARC in hemophiliacs, and, notably, improved liver dysfunction in these patients (Mori et al, 1990; Mori et al, 1989). It has also been effective in preventing the hepatic side effects of chemotherapy with a methotrexate combination or interferon (Akimoto et al; Hayashi et al), and in treating general hepatic failure (Acharya).

Enterohepatic cycling

One reason licorice is so effective in treatment of the liver is that it enters the enterohepatic loop, that is, it is excreted in the bile, then reabsorbed in the gut to recycle repeatedly through the liver (Ichikawa; Ishida).

Side effects and drug interactions

Licorice produces the well-documented side effect of hyperaldosteronism (hypertension, edema, hypokalemia) when taken in large doses (>50 g/day) or for long duration (>six weeks) (Wichtl). No such side effects have been observed in clinical trials of 40 ml SNMC/day for thirty days, or with 100 ml SNMC (200 mg glycyrrhizin/day) “for a short period” (Hikino). With widespread use of SNMC in Japan, hyperaldosteronism was seen with larger doses and extended use (SNMC). The side effect is reversible on discontinuation of glycyrrhizin. Licorice or glycyrrhizin may also interact with herbs or other medications containing cardiac glycosides (Wichtl).

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Copyright 2001 Paul Bergner