Eun-Jeon Park

Protective effect of curcumin in rat liver injury induced by carbon tetrachloride

This study was carried out to investigate the protective effects of curcumin on acute or subacute carbon tetrachloride‐induced liver damage in rats.

Curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro

We previously demonstrated that curcumin, a well‐known antioxidant, inhibits collagen deposition in carbon tetrachloride‐induced liver injury in rats. The major effector cells responsible for collagen synthesis 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 α‐actin proteins and of α1(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 α‐actin‐positive areas and lowered mRNA levels of type I collagen in the liver. In‐vitro, curcumin at a concentration of 5 μg mL−1 reduced DNA synthesis, and downregulated smooth muscle α‐actin and type I collagen expression, and α1(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.

Anti-fibrotic effects of a hot-water extract from Salvia miltiorrhiza roots on liver fibrosis induced by biliary obstruction in rats.

The anti‐fibrotic effects of a hot‐water extract form the traditional Chinese medicinal herb Salvia miltiorrhiza (Labiatae) on liver fibrosis induced by biliary obstruction was studied in rats. Liver fibrosis was induced in male Sprague‐Dawley rats by bile duct ligation and scission (BDL). After surgery, the hot‐water extract of S. miltiorrhiza roots (100 mg kg−1, p.o.) was administered daily for 28 days. The concentrations of aspartate transaminase, alanine transaminase, alkaline phosphatase, total bilirubin and total cholesterol in serum and hydroxyproline and malondialdehyde contents in liver were significantly increased in BDL rats. Treatment with the extract of S. miltiorrhiza significantly reduced (P < 0.01) the serum aspartate transaminase, alanine transaminase, alkaline phosphatase, and total cholesterol concentrations in BDL rats. The liver hydroxyproline content in BDL rats treated with extract was also reduced to 68% of that in BDL control rats (P < 0.01). The liver malondialdehyde content in BDL rats treated with the extract was also reduced to 47% of that in BDL control rats (P < 0.01). The morphological characteristics of fibrotic livers were improved in BDL rats treated with extract. Immunohistochemical examination of fibrotic liver showed that the extract of S. miltiorrhiza markedly reduced protein expression of α‐smooth muscle cell‐like actin, which indicates that hepatic stellate cell activation was inhibited during liver fibrosis development. The results indicate that the hot‐water extract of S. miltiorrhiza roots inhibits fibrosis and lipid peroxidation in rats with liver fibrosis induced by biliary obstruction.

Preventive effects of a purified extract isolated from Salvia miltiorrhiza enriched with tanshinone I, tanshinone IIA and cryptotanshinone on hepatocyte injury in vitro and in vivo

Salvia miltiorrhiza is traditionally used to treat liver disease in Asia. In this study, we tested the ability of a purified extract of S. miltiorrhiza (PF2401-SF) and its constituents, tanshinone I, tanshinone IIA, and cryptotanshinone, to protect against acute and subacute liver damage induced by carbon tetrachloride by measuring serum transaminase levels, the reduced form of glutathione (GSH), antioxidant enzyme activities, and lipid peroxidation levels in the liver. We also evaluated their ability to protect primary cultured rat hepatocytes from tertiary-butylhydroperoxide (tBH) or d-galactosamine (GalN). PF2401-SF was protective at 50-200mg/kg per day in acute liver injury and 25-100mg/kg per day in subacute liver injury. Tanshinone I, tanshinone IIA, and cryptotanshinon (40 microM), inhibited lactate dehydrogenase leakage, GSH depletion, lipid peroxidation and free radical generation in vitro. PF2401-SF and its major constituents, tanshinone I, tanshinone IIA and cryptotanshinone, can protect against liver toxicity in vivo and in vitro due to its antioxidant effects.

Scutellaria baicalensis inhibits liver fibrosis induced by bile duct ligation or carbon tetrachloride in rats

This study was carried out to investigate the antifibrotic effects of methanol extracts from the traditional Chinese medicinal herb, the root of Scutellaria baicalensis Georgi, on liver fibrosis induced by bile duct ligation and scission (BDL) or carbon tetrachloride (CCl4) in rats. Liver fibrosis was assessed by histological observations and by measuring levels of liver hydroxy‐proline, lipid peroxidation based on malondialdehyde (MDA) production, and serum enzyme activities. The morphological characteristics of liver tissue were examined by Massons trichrome staining and immunostaining against smooth muscle cell α‐actin. In both models, the levels of hydroxyproline and MDA in liver were significantly increased. Treatment with a methanol extract of S. baicalensis significantly reduced the levels of liver hydroxyproline and MDA, with improved histological findings. In both models, the liver areas positive for smooth muscle cell α‐actin were considerably decreased by treatment with oral methanol extract of S. baicalensis (150 mg kg−1 daily for 28 days). A methanol extract of S. baicalensis root inhibits fibrosis and lipid peroxidation in rat liver induced by BDL or CCl4.

Protective effect of Rhodiola sachalinensis extract on carbon tetrachloride-induced liver injury in rats

This study was carried out to investigate the protective effect of an aqueous extract from the root of Rhodiola sachalinensis (RSE) on liver injury induced by repetitive administration of carbon tetrachloride in rats. RSE was given orally to rats at doses of 50, 100 or 200 mg/kg throughout the carbon tetrachloride treatment for 28 days. In rats treated with carbon tetrachloride, the levels of hydroxyproline and malondialdehyde (MDA) in the liver, and serum enzyme activities were significantly increased. RSE treatment significantly reduced the levels of liver hydroxyproline and MDA, and serum enzyme activities, in accordance with improved histological findings. Immunohistological findings indicated RSE treatment inhibited hepatic stellate cell activation, which is a major step for collagen accumulation during liver injury. These data suggest that RSE protects the liver from repetitive injury induced by carbon tetrachloride in rats.

The ethanol-soluble part of a hot-water extract from Artemisia iwayomogi inhibits liver fibrosis induced by carbon tetrachloride in rats.

This study was carried out to investigate the protective effects of the hot‐water extract from Artemisia iwayomogi (Compositae) on carbon tetrachloride‐induced liver fibrosis in rats.

Antifibrotic effect of extracellular biopolymer from submerged mycelial cultures ofCordyceps militaris on liver Fibrosis induced by Bile duct ligation and scission in rats

The antifibrotic effects of hot water extract (WEC), intracellular biopolymer (IPC) and extracellular biopolymers (EPC) from myceiial liquid culture ofCordyceps 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.

An isocoumarin with hepatoprotective activity in Hep G2 and primary hepatocytes from Agrimonia pilosa.

Phytochemical investigation of the aqueous extract of the roots of Agrimonia pilosa Ledeb. (Rosaceae), as guided by hepatoprotective activityin vitro, furnished two isocoumarins, agrimonolide (1) and agrimonolide 6-O-β-D-glucoside (3), and (+)-catechin (2). Compound 1 showed hepatoprotective effects on both tacrine-induced cytotoxicity in human liver-derived Hep G2 cells andtert-butyl hydroperoxide-induced cytotoxicity in rat primary hepatocytes with EC50 values of 88.2 ± 2.8 and 37.7 ± 1.6 μM, respectively.

Tanshinone II A Induces Apoptosis and S Phase Cell Cycle Arrest in Activated Rat Hepatic Stellate Cells

Tanshinone IIA, a major component extracted from the traditional herbal medicine, Salvia miltiorrhiza Bunge, improves blood circulation and treats chronic hepatitis and hepatic fibrosis. Activation of hepatic stellate cells (HSCs) is the predominant event in liver fibrosis. The therapeutic goal in liver fibrosis is the reversal of fibrosis and selective clearance of activated HSCs. We used rat HSCs transformed by Simian virus 40 (t-HSC/Cl-6) to overcome the limitations inherent in studying subcultures of HSCs. Treatment of t-HSC/Cl-6 cells with tanshinone IIA inhibited cell viability in a dose- and time-dependent manner. Tanshinone IIA induced apoptosis as demonstrated by DNA fragmentation, poly(ADP-ribose) polymerase and caspase-3 cleavage, increased Bax/Bcl-2 protein ratio, and depolarization of mitochondrial membranes to facilitate cytochrome c release into the cytosol. Furthermore, this compound markedly induced S phase cell cycle arrest, and down-regulated cyclins A and E, and cdk2. Thus, tanshinone IIA induces apoptosis and S phase cell cycle arrest in rat HSCs in vitro.