Effects and their binding sites of glycyrrhetinic acid and glycyrrhizin on isolated rat hepatocyte membrane.

Gu, Yundi; Zhou, Fangcheng; Yang, Shanmai; Zhang, Jianxia; Jin, Shi; Cheng, Lingzhong

(Department of Histology and Embryology, School of Basic Medical Sciences, Shanghai Medical University, Shanghai 200032, Peop. Rep. China).

Shanghai Yike Daxue Xuebao, 27(4), 270-273 (Chinese) 2000

The effects and their binding sites of glycyrrhetinic acid and glycyrrhizin on isolated rat hepatocyte membrane were studied. Hepatocytes were isolated from the normal rat livers by collagenase pouring into circulation and were cultured with D-Hanks soln., Zhuling polysaccharides, glycyrrhizin and glycyrrhetinic acid resp. in vitro. After 24 h, The hepatocytes were collected and obsd. under electron microscope, and colloidal gold probe was used to detect the binding sites of the glycyrrhizin and glycyrrhetinic acid on the surface of the hepatocytes. Under scanning electron microscope, hepatocytes treated with the glycyrrhetinic acid exhibited a surface with abundant smooth- surfaced bleb-like processes of various size and were devoid of microvilli; under transmission electron microscope, concd. colloidal gold granules in black were obviously seen at the surface of hepatocytes treated with glycyrrhetinic acid-bovine serum albumin-colloidal gold granule probe. The biol. effect and the binding sites of glycyrrhetinic acid on the surface of hepatocytes were more remarkable than that of glycyrrhizin.

 

Effects of glycyrrhizin and glycyrrhetinic acid on damage to isolated hepatocytes by transient exposure to tert-butyl hydroperoxide.

Takayama, Fusako; Egashira, Toru; Yamanaka, Yasumitsu

(Department of Pharmacology, Oita Medical University, Japan).

Yakuri to Chiryo, 28(9), 763-770 (Japanese) 2000

We investigated the effects of glycyrrhizic (GL) and glycyrrhetinic acid (GA) which are applied to allergic reaction and inflammatory disease, on the damage to isolated rat hepatocytes transiently exposed to 75 mM tert-Bu hydroperoxide (t-BuOOH). In t-BuOOH-exposed cells, the level of phosphatidylcholine hydroperoxide (PCOOH), a peroxidative product of biomembranes in the hepatocytes, and the leakage of acid phosphatase (AP), a lysosomal enzyme, AST, ALT and LDH into the culture medium, were significantly increased above the background levels found in control expts. In t-BuOOH-exposed cells, the level of phosphatidylcholine (PC) was significantly (p < 0.05) decreased. By ESR spectroscopy anal. using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), spin adducts of carbon center radicals and hydroxyl radicals (DMPO-OH) were detected after t-BuOOH exposure for 15 min. GL and GA (2, 20 nM) added to culture medium before and during the t-BuOOH exposure, could not changed the increased PCOOH level, but improved the decreased PC level in hepatocytes and the leakage of AP, AST, ALT and LDH into the culture medium. GL and GA also reduced the DMPO-OH formation in hepatocyte suspension, although they have not radical scavenging abilities. These results suggest that GL and GA exert their protective effects by the membrane stabilization which results in inhibiting the prolongation of oxidative stress.

The protective effect of glycyrrhizin against injury of the liver caused by ischemia-reperfusion.

Nagai, Takayuki; Egashira, Toru; Yamanaka, Yasumitsu; Kohno, Masahiro

(Dep. Pharmacol., Med. Coll. Oita, Oita 879-56, Japan).

Arch. Environ. Contam. Toxicol., 20(3), 432-6 (English) 1991.

Effects of glycyrrhizin (GR) on in vivo injury of the rat liver caused by ischemia-reperfusion were detd. Levels of serum transaminases (AST, ALT) and lactate dehydrogenase (LDH), lipid peroxides in the liver, and blood superoxide dismutase activity were increased. The total glutathione content in the liver was decreased. GR given at 100 mg/kg s.c. for 10 days suppressed the elevation of the lipid peroxide level, serum AST, ALT, LDH level, and the decrease in glutathione content during reperfusion. The suppressive effect of GR was similar with that of a-tocopherol (VE). GR showed neither 1,1-diphenyl-2-picrylhydrazyl (DPPH) nor 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-OOH radical-trapping ability, but exhibited DMPO-OH radical-trapping action. VE exhibited both DPPH and DMPO-OOH radical-trapping ability. The hydroxyl radical trapping action of GR is the likely mechanism suppressing liver injury caused by ischemia-reperfusion.

Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats.

Shimizu, Ichiro; Ma, Yue-Rong; Mizobuchi, Yoko; Fei, Liu; Miura, Tetsuo; Nakai, Yoichiro; Yasuda, Mitugi; Shiba, Masako; Horie, Takahiro; Amagaya, Sakae; Kawada, Norifumi; Hori, Hitoshi; Ito, Susumu

(Second Department of Internal Medicine, School of Medicine, University of Tokushima, Tokushima, Japan).

Hepatology (Philadelphia), 29(1), 149-160 (English) 1999

It has been shown that lipid peroxidn. is assocd. with hepatic fibrosis and stellate cell activation. Shosaiko-to (TJ-9) is an herbal medicine, which is commonly used to treat chronic hepatitis in Japan, although the mechanism by which TJ-9 protects against hepatic fibrosis is not known. As a result, we assayed the preventive and therapeutic effects of TJ-9 on exptl. hepatic fibrosis, induced in rats by dimethylnitrosamine (DMN) or pig serum (PS), and on rat stellate cells and hepatocytes in primary culture, and assessed the antioxidative activities and the active components of TJ-9. Male Wistar rats were given a single i.p. injection of 40 mg/kg DMN or 0.5 mL PS twice weekly for 10 wk. In each model, rats were fed a basal diet throughout, or the same diet, which also contained 1.5% TJ-9, for 2 wk before treatment or for the last 2 wk of treatment. TJ-9 suppressed the induction of hepatic fibrosis, increased hepatic retinoids, and reduced the hepatic levels of collagen and malondialdehyde (MDA), a prodn. of lipid peroxidn. Immunohistochem. examn. showed that TJ-9 reduced the deposition of type I collagen and the no. of a-smooth muscle actin (a-SMA) pos.-stellate cells in the liver and inhibited, not only lipid peroxidn. in cultured rat hepatocytes that were undergoing oxidative stress, but also the prodn. of type I collagen, a-SMA expression, cell proliferation, and oxidative burst in cultured rat stellate cells. In addn., TJ-9 inhibited Fe2+/ADP-induced lipid peroxidn. in rat liver mitochondria in a dose-dependent manner and showed radical scavenging activity. Among the active components of TJ-9, baicalin and baicalein were found to be mainly responsible for the antioxidative activity. These findings suggest that Sho-saiko-to (TJ-9) functions as a potent antifibrosuppressant by inhibition of lipid peroxidn. in hepatocytes and stellate cells in vivo.

Effects of glycyrrhizin on the serum biochemical indexes in patients with liver cirrhosis.

Wang, Qi; Guo, Wendong; Xiao, Jinmei; Gao, Ying; Wang, Huiyun (Dept. of Gastroenterology, 2nd Clinical Medical College, Shanxi Medical University, Taiyuan 030001, Peop. Rep. China).

Shanxi Yike Daxue Xuebao, 29(2), 102-103 (Chinese) 1998

Objective: To observe the curative effect of glycyrrhizin as an anti-lipid peroxidn. drug on patients with liver cirrhosis. Methods: Forty patients with liver cirrhosis received glycyrrhizin injection (80 mL/d), and serum SOD, LPO, GSH-Px, GSH, ALT and bilirubin were measured before treatment and after 4 wk. Results: SOD and GSH-Px activities were decreased and LPO were increased in patients with liver cirrhosis. After treatment, SOD and GSH-Px were increased and LPO, ALT and bilirubin were decreased. Conclusion: It is considered that glycyrrhizin is an anti-lipid peroxidn. drug.

Inhibitory effect of glycyrrhizin on NF-kB binding activity in CCl4- plus ethanol-induced liver cirrhosis in rats.

Wang, Ji-Yao; Guo, Jin-Sheng; Li, Hai; Liu, Shu-Ling; Zern, Mark A.

(Department of Gastroenterology, ZhongShan Hospital, Shanghai Medical University, Shanghai, Peop. Rep. China).

Liver (Copenhagen), 18(3), 180-185 (English) 1998

Potenlini is an injectable compd. whose active component is glycyrrhizin, which is extd. from licorice. Previous studies showed that it could reduce liver injury, improve alanine aminotransferase (ALT) levels and act as an antifibrotic agent. However, the mechanism of its action remains unclear. The aim of this study was to det. the mol. mechanism of its action by investigating the effects of potenlini on nuclear factor-kB(NF-kB) binding activity in an animal model of liver cirrhosis. Rats were randomly allocated into a normal control group, a model control group, and a potenlini group. Rats in the latter two groups were treated with CCl4 and ethanol soln. in order to induce chronic liver injury. Rats in the potenlini group were given potenlini treatment at the same time. Serum ALT levels were significantly reduced in rats treated with potenlini compared with levels in rats of the model control group, which had dramatically increased ALT levels. Histol., liver steatosis and fibrosis were severe in the rats of the model group, but were significantly improved in rats of the potenlini group. NF-kB binding activity was markedly increased in the liver specimens taken from the rats of the model control group in comparison with the binding of normal livers, but the binding levels were nearly normal in the livers of the potenlini group. The results suggest that potenlini can inhibit the NF-kB binding activity in CCl4 and ethanol-induced chronic liver injury, and that effect may be a possible mechanism by which potenlini protects the liver from hepatotoxin-induced liver injury and cirrhosis.

Studies on the regulation by drugs against experimental hepatitis. 1. The therapeutical effects of glycyrrhizinic acid, DL-methionine, their mixture and tablets against acute injury induced by carbon tetrachloride or D-galactosamine.

Fujita, Haruhisa; Sakurai, Toshiharu; Toyoshima, Shigeshi

(Sch. Med., Keio Univ., Tokyo, Japan).

Oyo Yakuri, 16(4), 637-45 (Japanese) 1978.

The optimum doses of glycyrrhizinic acid (I) [1405-86-3] and DL-methionine [59-51-8] for treatment of rat hepatic failure induced by CCl4 or d-galactosamine were 100 mg/kg/day, whereas that of a glycyrrhizinic acid-DL-methionine mixt. [70055-51-5] was 50 mg/kg/day for each compd. The mixt. had greater therapeutic effects than its components alone.

Study on the regulation by drugs against experimental hepatitis. 2. The therapeutical effects of glycyrrhizinic acid, DL-methionine and their complex against chronical liver injury induced by D-galactosamine in rats.

Fujita, Haruhisa; Sakurai, Toshiharu; Toyoshima, Shigeshi

(Sch. Med., Keio Univ., Tokyo, Japan).

Oyo Yakuri, 16(4), 647-57 (Japanese) 1978.

Glycyrrhizinic acid (I) [1405-86-3], DL-methionine [59-51-8], and a glycyrrhizinic acid-methionine mixt. [70055-51-5] administered to rats with hepatitis induced by d-galactosamine [7535-00-4] prevented the increase of liver wt. due to galactosamine administration. Histol. examn. showed a marked improvement in the development of biliary duct after the administration of the mixt. These 3 agents produced no side effects within 3 mo and improved the increase of body wt.