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).

References:

Acharya SK, Dasarathy S, Tandon A, Joshi YK, Tandon BN. “A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure.” Indian J Med Res 1993 Apr;98:69-74

Abdugafurova MA, Li VS, Sherstnev MP, Atanaev TB, et al. “Antioxidative properties of glycyrrhyzic acid salts and their effect on the liver monooxygenase system.” Vopr Mad Khim 1990 Sep-Oct;36(5):29-31

Akimoto M, Kimura M, Sawano A, Iwasaki H, et al. “Prevention of cancer chemotherapeutic agent-induced toxicity in postoperative breast cancer patients with glycyrrhizin (SNMC).” Gan No Rinsho 1986 Jul;32(8):869-72

Bensky D, Gamble A. Chinese Herbal Medicine: Materia Medicare Eastland Press. Seattle. 1986

Crance JM, Biziagos E, Passagot J, van Cuyck-Gandrë H, Deloince R “Inhibition of hepatitis A virus replication in vitro by antiviral compounds.” J Med Virol 1990 Jun;31(2): 155-60

Hayashi J, Kashiwagi S, Noguchi A, Ikematsu H, et al. “Combination therapy of glycyrrhizin withdrawal and human fibroblast interferon for chronic hepatitis B.” Clin Ther 1989;11(1):161-9

Hikino. “Natural products for liver diseases” 1988 Economic and Medicinal Plant Research Volume 2 (39-67)

Ishida S; Sakiya Y; Ichikawa T; Awazu S. “Pharmacokinetics of glycyrrhetic acid, a major metabolite of glycyrrhizin, in rats.”Chem Pharm Bull (Tokyo) 1989 Sep;37(9):2509-13

Ichikawa T, Ishida S, Sakiya Y, Sawada Y, et al. “Biliary excretion and enterohepatic cycling of glycyrrhizin in rats.” J Pharm Sci 1986 Jul;75(7):672-5

Ju HS, Li XJ, Zhao BL, Han ZW, Xin WJ. “Effects of glycyrrhiza flavonoid on lipid peroxidation and active oxygen radicals ”Yao Hsueh Hsueh Pao 1989;24(11):807-12

Kimura M, Watanabe H, Abo T. “Selective activation of extrathymic T calls in the liver by glycyrrhizin.” Biotherapy 1992;5(3): 167-76

Kiso Y, Tohkin M, Hikino H, Hattori M, et al. “Mechanism of anti-hepatotoxic activity of glycyrrhizin. I: Effect on free radical generation and lipid peroxidation.” Planta Med 1984 Aug;50(4):298-302

Kraus S. “The Anti-estrogenic action of beta-glycyrrhetinic acid.” Exp Med Surg 1969;27:411-420

Kumada H, Yoshida Y, Ikeda K, Koyake E, Yoshiba A. “Study on frequency of the eAg-eAb seroconversion by corticosteroid and glycyrrhizin in eAg positive chronic hepatitis (author’s transl)” Nippon Shokakibyo Gakkai Zasshi 1981 Nov;78(11):2195

Kumagai A, Nishino K, Shimomura A, Kin T, Yamamura Y, “Effect of glycyrrhizin on estrogen action.” Endocrinol Jpn 1967 Mar;14(1):34-8

Leung, AY. Encyclopedia of Common Natural Ingredients used in Food Drugs and Cosmetics. John Wiley and Sons, New York. 1980.

The Merck Index Eleventh Ed. Merck and Company. rahway, NJ. 1989

Matsunami H, Lynch SV, Balderson GA, Strong RW. “Use of glycyrrhizin for recurrence of hepatitis B after liver transplantation [letter] Am J Gastroenterol 1993 Jan;88(1):152-3

Mizoguchi Y, Katoh H, Tsutsui H, Yamamoto S, Morisawa S. “Protection of liver cells from experimentally induced liver cell injury by glycyrrhizin.” Gastroenterol Jpn 1985 Apr;20(2):99-103

Nakamura T, Fuji T, Ichihara A. “Enzyme leakage due to change of membrane permeability of primary cultured rat hepatocytes treated with various hepatotoxins and its prevention by glycyrrhizin.” Cell Biol Toxicol 1985 Oct;1(4):285-95.

Ohta W, Iwamura K. “Treatment of non-A, non-B hepatitis with glycyrrhizin.” Nippon Rinsho 1988 Dec;46(12):2681-8

Ozaki Y, Noguchi M, Kamakura H, Harada M. “Studies on concentration of glycyrrhizin in plasma and its absorption after oral administration of licorice extract and glycyrrhizin.”

Yakugaku Zasshi 1990 Jan; 110(1):77-81

Pizzomo J, Murray M. A Textbook of Natural Medicine. Bastyr College Publications, Seattle. 1989

Sharaf A, Goma N. “Phytoestrogens and their antagonism to progesterone and testosterone.” J Endocrinol 1965; 31:289-290

Shibayama Y. “Prevention of hepatotoxic responses to chemicals by glycyrrhizin in rats.” Exp Mol Pathol 1989 Aug;51(1):48-55

Shiki Y, Shirai K, Saito Y, Yoshida S, et al. “Effect of glycyrrhizin on lysis of hepatocyte membranes induced by anti-liver cell membrane antibody.” J Gastroenterol Hepatol 1992 Jan-Feb;7(1):12-6

Shinada M, Azuma M, Kawai H, Sazaki K. “Enhancement of interferon-gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus.” Proc Soc Exp Biol Meal 1986 Feb;181(2):205-10

Su XS, Chen HM, Wang LH, Jiang CF, et al. “Clinical and laboratory observation on the effect of glycyrrhizin in acute and chronic viral hepatitis.” SO - J Tradit Chin Med 1984 Jun;4(2):127-32

Suzuki H, Ohta Y, Takino T, Fujisawa K, et al. “Effects of glycyrrhizin on biochemical tests in patients with chronic hepatitis — double blind trial.” Asian Med J 1984; 26:423-438

Tamaya T, Sato S, Okada H, “Inhibition by plant herb extracts of steroid bindings in uterus, liver and serum of the rabbit.” Acta Obstet Gynecol Scand 1986;65(8):839-842

Tan YZ. “Effect of glycyrrhiza on liver microsomal enzymes in mouse liver homogenates.” Chung Yao Tung Pao 1986 Oct;11(10):55-6

Wang JT. “A double-blind study of strong neominophagen-C in treating chronic hepatitis.” Chung Hua Nei Ko Tsa Chih 1984 Jan;23(1):14-8, 62

Wichtl M. Teedrogen. Wissenschaftliche Verlagsgesellschaft MbH, Stuttgart. 1989.

Zhang ZH, Yang ZH. “Effect of adenine-arabinosine with glycyrrhizin in treating chronic active hepatitis” Chung Hsi I Chieh Ho Tsa Chih 1988 Mar;8(3):150-1,157, 132-3

Zhao MQ, Hah DW, Ma XH, Zhao YC, et al. “Preventive and therapeutic actions of glycyrrhizin, glycyrrhetic acid and crude saikosides on experimental liver cirrhosis in rats.” Yao Hsueh Hsueh Pao 1983 May;18(5):325-31
 
Copyright 2001 Paul Bergner 




click medherb.com below to search site

 
AUDIO CD-ROM COURSES
Medical Herbalism. Introductory, Advanced, Clinical. CE Available.

FIRST COURSE IN MEDICAL HERBALISM With Resources Kit. Learn 14 herbs, Make your own herbal medicines.

CLASSROOM EDUCATION Medical Herbalism. Advanced and Clinical Programs. Occupational Certification.

Mountain Rose Herbs. A Herbs, Health and Harmony C