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Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis.

Li JP, Gao Y, Chu SF, Zhang Z, Xia CY, Mou Z, Song XY, He WB, Guo XF, Chen NH - Acta Pharmacol. Sin. (2014)

Bottom Line: Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues.Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes.Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro.

View Article: PubMed Central - PubMed

Affiliation: State Key of Laboratory Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

ABSTRACT

Aim: To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol- and CCl4-induced hepatic fibrosis in rats and to explore the mechanisms of the effects.

Methods: Rats were given 6% alcohol in water and injected with CCl4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and α-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies.

Results: In the alcohol- and CCl4-treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 μmol/L) induced Nrf2 translocation, and suppressed CCl4-induced cell proliferation, reversed CCl4- induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and α-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro.

Conclusion: Rg1 exerts protective effects in a rat model of alcohol- and CCl4-induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes.

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Related in: MedlinePlus

Effect of Rg1 on CCl4-induced changes in the levels of hepatic antioxidant enzyme activities and lipid peroxidation. The activities of antioxidant enzyme and level of lipid peroxidation in the liver (n=6) were determined and the data are shown as follows: MDA levels (A), CAT activities (B), GPX activities (C), SOD activities (D), Western bloting analysis of SOD protein (E). Representative blots were from three independent experiments. The data were expressed as mean±SD. bP<0.05, cP<0.01 vs control. eP<0.05, fP<0.01 vs CCl4 alone.
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fig5: Effect of Rg1 on CCl4-induced changes in the levels of hepatic antioxidant enzyme activities and lipid peroxidation. The activities of antioxidant enzyme and level of lipid peroxidation in the liver (n=6) were determined and the data are shown as follows: MDA levels (A), CAT activities (B), GPX activities (C), SOD activities (D), Western bloting analysis of SOD protein (E). Representative blots were from three independent experiments. The data were expressed as mean±SD. bP<0.05, cP<0.01 vs control. eP<0.05, fP<0.01 vs CCl4 alone.

Mentions: The levels of MDA were monitored to evaluate the effect of Rg1 treatment on alcohol- and CCl4-induced liver lipid peroxidation. A significant increase of MDA showed that oxidative damage was induced in the untreated fibrosis group (8.61±0.94 nmol/mg protein, P<0.001, Figure 5A). Treatment with Rg1 (10, 20, and 40 mg/kg) significantly decreases the lipid peroxidation compared with the model group (7.14±0.65, 6.61±0.41, and 6.30±0.35 nmol/mg protein; P<0.05, P<0.01 and P<0.001, respectively. Figure 5A).


Nrf2 pathway activation contributes to anti-fibrosis effects of ginsenoside Rg1 in a rat model of alcohol- and CCl4-induced hepatic fibrosis.

Li JP, Gao Y, Chu SF, Zhang Z, Xia CY, Mou Z, Song XY, He WB, Guo XF, Chen NH - Acta Pharmacol. Sin. (2014)

Effect of Rg1 on CCl4-induced changes in the levels of hepatic antioxidant enzyme activities and lipid peroxidation. The activities of antioxidant enzyme and level of lipid peroxidation in the liver (n=6) were determined and the data are shown as follows: MDA levels (A), CAT activities (B), GPX activities (C), SOD activities (D), Western bloting analysis of SOD protein (E). Representative blots were from three independent experiments. The data were expressed as mean±SD. bP<0.05, cP<0.01 vs control. eP<0.05, fP<0.01 vs CCl4 alone.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4125711&req=5

fig5: Effect of Rg1 on CCl4-induced changes in the levels of hepatic antioxidant enzyme activities and lipid peroxidation. The activities of antioxidant enzyme and level of lipid peroxidation in the liver (n=6) were determined and the data are shown as follows: MDA levels (A), CAT activities (B), GPX activities (C), SOD activities (D), Western bloting analysis of SOD protein (E). Representative blots were from three independent experiments. The data were expressed as mean±SD. bP<0.05, cP<0.01 vs control. eP<0.05, fP<0.01 vs CCl4 alone.
Mentions: The levels of MDA were monitored to evaluate the effect of Rg1 treatment on alcohol- and CCl4-induced liver lipid peroxidation. A significant increase of MDA showed that oxidative damage was induced in the untreated fibrosis group (8.61±0.94 nmol/mg protein, P<0.001, Figure 5A). Treatment with Rg1 (10, 20, and 40 mg/kg) significantly decreases the lipid peroxidation compared with the model group (7.14±0.65, 6.61±0.41, and 6.30±0.35 nmol/mg protein; P<0.05, P<0.01 and P<0.001, respectively. Figure 5A).

Bottom Line: Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues.Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes.Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro.

View Article: PubMed Central - PubMed

Affiliation: State Key of Laboratory Bioactive Substances and Functions of Natural Medicines, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

ABSTRACT

Aim: To investigate the anti-fibrosis effects of ginsenoside Rg1 on alcohol- and CCl4-induced hepatic fibrosis in rats and to explore the mechanisms of the effects.

Methods: Rats were given 6% alcohol in water and injected with CCl4 (2 mL/kg, sc) twice a week for 8 weeks. Rg1 (10, 20 and 40 mg/kg per day, po) was administered in the last 2 weeks. Hepatic fibrosis was determined by measuring serum biochemical parameters, HE staining, Masson's trichromic staining, and hydroxyproline and α-SMA immunohistochemical staining of liver tissues. The activities of antioxidant enzymes, lipid peroxidation, and Nrf2 signaling pathway-related proteins (Nrf2, Ho-1 and Nqo1) in liver tissues were analyzed. Cultured hepatic stellate cells (HSCs) of rats were prepared for in vitro studies.

Results: In the alcohol- and CCl4-treated rats, Rg1 administration dose-dependently suppressed the marked increases of serum ALT, AST, LDH and ALP levels, inhibited liver inflammation and HSC activation and reduced liver fibrosis scores. Rg1 significantly increased the activities of antioxidant enzymes (SOD, GSH-Px and CAT) and reduced MDA levels in liver tissues. Furthermore, Rg1 significantly increased the expression and nuclear translocation of Nrf2 that regulated the expression of many antioxidant enzymes. Treatment of the cultured HSCs with Rg1 (1 μmol/L) induced Nrf2 translocation, and suppressed CCl4-induced cell proliferation, reversed CCl4- induced changes in MDA, GPX, PCIII and HA contents in the supernatant fluid and α-SMA expression in the cells. Knockdown of Nrf2 gene diminished these actions of Rg1 in CCl4-treated HSCs in vitro.

Conclusion: Rg1 exerts protective effects in a rat model of alcohol- and CCl4-induced hepatic fibrosis via promoting the nuclear translocation of Nrf2 and expression of antioxidant enzymes.

Show MeSH
Related in: MedlinePlus