This study was carried out to investigate the protective effects of curcumin on acute or subacute carbon tetrachloride-induced liver damage in rats. Acute hepatotoxicity was induced by intraperitoneal injection of carbon tetrachloride after 4 consecutive days of curcumin treatment. Subacute hepatotoxicity was induced by oral administration of carbon tetrachloride twice a week during 4 weeks of curcumin treatment. In rats with acute liver injury, curcumin (100 and 200 mg kg(-1)) lowered the activity of serum alanine aminotransferase to 52-53% (P < 0.05) and aspartate aminotransferase to about 62% (P < 0.05) those of control rats. In rats with subacute liver injury, curcumin (100 mg kg(-1)) lowered the activity of serum alanine aminotransferase to 34% (P < 0.01) and alkaline phosphatase to 53% (P < 0.05) of control rats. The liver hydroxyproline content in the curcumin (100 mg kg(-1))-treated group was reduced to 48% of the carbon tetrachloride control group (P < 0.01). Malondialdehyde levels in curcumin (100 mg kg(-1)) treated rat liver was decreased to 67% of the control rat liver (P < 0.01) in subacute injury. It was concluded that curcumin improved both acute and subacute liver injury induced by carbon tetrachloride in rats.

Tetrandrine, an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to elicit antifibrotic effects in various cell types. In the present study, the effect of tetrandrine on liver fibrosis was investigated by using bile duct ligation and scission in rats as a model of hepatic fibrosis. Treatment with tetrandrine in fibrotic rats reduced serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels to 72%, 52% and 51% that of controls at 10 mg/kg/day, respectively. Liver hydroxyproline contents in tetrandrine-treated rats with bile duct ligation and scission were also reduced to 65% of that of control rats with bile duct ligation and scission at 10 mg/kg/day. The morphological characteristics of fibrotic liver, which appeared in control bile duct ligation and scission group, were improved in tetrandrine-treated bile duct ligation and scission group. We also examined the effect of tetrandrine on cultured rat hepatic stellate cells, which plays an important role in the pathogenesis of hepatic fibrosis, activation to investigate whether it could act mainly by direct action on rat hepatic fibroblastic cells. In cultured rat hepatic stellate cells, tetrandrine reduced DNA synthesis to 57% of control hepatic stellate cells at 10 mg/ml without affecting cell viability. Smooth muscle-a-actin expression, the phenotypic marker of activated hepatic stellate cells, was also decreased. We conclude that tetrandrine has an antifibrotic effect on liver fibrosis in rats induced by bile duct ligation and scission, indicating that it might exert a direct effect on rat hepatic stellate cells.Hepatic fibrosis is a consequence of severe liver damage that occurs in many patients with chronic liver disease. Regardless of many different causes, hepatic fibrosis is characterized by increased and altered deposition of newly formed extracellular matrix components such as collagens, proteoglycans, fibronectin and hyaluronic acid (Friedman 1993), leading to the complication of portal hypertension and hepatic failure.In the injured liver, these extracellular matrix components are produced in hepatic stellate cells in the space of Disse, which function in intact liver lobules as the primary storage area for retinoids (Hendrisks et al. 1985). During the course of ongoing liver fibrogenesis, hepatic stellate cells acquire myofibroblastic features, proliferate (Friedman et al. 1989;Hautekeete & Geerts 1997), synthesize increased amounts of extracellular matrix components (Shiratori et al. 1987) and express smooth muscle-a-actin . The transformation of hepatic stellate cells into myofibroblast-like cells is recognized as a critical step in hepatic fibrosis. Therefore, this cell type is an important target for antifibrotic therapy.Tetrandrine is a bis-benzyl isoquinoline alkaloid derived from Stephania tetrandra (Moore). This compound has been characterized pharmacologically to exhibit hypotensive, immunosuppressive properties (Sutter & Wang 1993), and inhibition of lipid perox...

We previously demonstrated that curcumin, a well-known antioxidant, inhibits collagen deposition in carbon tetrachloride-induced liver injury in rats. The major effector cells responsibleforcollagensynthesis in the liver are activated hepatic stellate cells. In this study,we investigated the inhibitory effects of curcumin on the collagen synthesis and activation of rat hepatic stellate cells in-vitro, and on hepatic stellate cell activation in-vivo. The effects of curcumin on the production of collagen and smooth muscle alpha-actin proteins and of alpha1(I) collagen mRNA were studied in-vivo and in-vitro. The effect of curcumin on DNA synthesis was also determined in-vitro. In-vivo, treatment with curcumin reduced collagen deposition and smooth muscle alpha-actin-positive areas and lowered mRNA levels of type I collagen in the liver. In-vitro, curcumin at a concentration of 5 microg mL(-1) reduced DNA synthesis, and downregulated smooth muscle alpha-actin and type I collagen expression, and alpha1(I) collagen mRNA expression. We concluded that curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro, and thus may prove a valuable anti-fibrogenic agent.

The aim of this study was to investigate the protective effect of honokiol and magnolol on hepatocyte injury induced by either tertiary butyl hydroperoxide (tBH)- or D-galactosamine (GalN). The cellular leakage of LDH and AST, and cell death by treatment with 1.5 mM tBH for 1 h, were significantly inhibited by treatment with honokiol (40 and 20 microM) or magnolol (40 microM). Treatment with honokiol or magnolol significantly inhibited lipid peroxidation in both cells and media, the generation of intracellular reactive oxygen species (ROIs), and intracellular glutathione (GSH) depletion induced by tBH. The cellular leakage of LDH and AST, and cell death, by 24-hour treatment with 30 mM GalN were significantly inhibited by treatment with honokiol (20, 5 and 1 microM) or magnolol (20, 5 and 1 microM). Treatment with honokiol (20, 5 and 1 microM) or magnolol (20 and 5 microM) significantly inhibited the intracellular GSH depletion induced by GalN. The hepatoprotective effects of honokiol and magnolol on oxidative stress induced by tBH were probably the result of their antioxidant activity. Honokiol and magnolol also had a protective effect against GalN-induced hepatotoxicity, which was used as an alternate model to oxidative stress, acting by inhibiting intracellular GSH depletion.

The antifibrotic effects of hot water extract (WEC), intracellular biopolymer (IPC) and extracellular biopolymers (EPC) from mycelial liquid culture of Cordyceps militaris on liver fibrosis were studied. Liver fibrosis was induced by a bile duct ligation and scission (BDL/S) operation, duration of 4 weeks in rats. In BDL/S rats, the levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin in serum and hydroxyproline content in liver were dramatically increased. The WEC or IPC treatment (30 mg/kg/day for 4 weeks, p.o.) in BDL/S rats reduced the serum AST, ALT and ALP levels significantly (p<0.01). The EPC treatment (30 mg/kg/day for 4 weeks, p.o.) reduced the serum ALT, AST and ALP levels significantly (p<0.01). Malondialdehyde contents in liver treated with WEC, IPC or EPC were significantly reduced (p<0.05). But Liver hydroxyproline content was decreased only in EPC treated BDL/S rats to 55% that of BDL/S control rats (p<0.01). The morphological characteristics and expression of alpha smooth muscle like actin in fibrotic liver, which appeared in BDL/S control group were improved in EPC treated fibrotic liver. These results indicate that EPC (30 mg/kg/day for 4 weeks, p.o.) has an antifibrotic effect on fibrotic rats induced by BDL/S.