Ginseng extract and ginsenoside Rb1 attenuate carbon tetrachloride-induced liver fibrosis in rats

Abstract

Background: Ginsenosides, the major bioactive compounds in ginseng root, have been found to have antioxidant, immunomodulatory and anti-inflammatory activities. This study investigated the effects of ginsenosides on carbon tetrachloride (CCl4)-induced hepatitis and liver fibrosis in rats.

Methods: Male Sprague-Dawley rats were randomly divided into four groups: control, CCl4, CCl4 + 0.5 g/kg Panax ginseng extract and CCl4 + 0.05 g/kg ginsenoside Rb1 groups. The treated groups were orally given Panax ginseng extract or ginsenoside Rb1 two weeks before the induction of liver injury for successive 9 weeks. Liver injury was induced by intraperitoneally injected with 400 ml/l CCl4 at a dose of 0.75 ml/kg body weight weekly for 7 weeks. The control group was intraperitoneally injected with olive oil.

Results: The pathological results showed that ginsenoside Rb1 decreased hepatic fat deposition (2.65 ± 0.82 vs 3.50 ± 0.75, p <0.05) and Panax ginseng extract lowered hepatic reticular fiber accumulation (1.05 ± 0.44 vs 1.60 ± 0.39, p <0.01) increased by CCl4. Plasma alanine aminotransferase and aspartate aminotransferase activities were increased by CCl4 (p <0.01), and aspartate aminotransferase activity was decreased by Panax ginseng extract at week 9 (p <0.05). Exposure to CCl4 for 7 weeks, the levels of plasma and hepatic triglycerides (p <0.01), hepatic cholesterol (p <0.01), interleukin-1β (p <0.01), prostaglandin E2 (p <0.05), soluble intercellular adhesion molecule-1 (p <0.05), hydroxyproline (p <0.05), matrix metalloproteinase-2 (p <0.05) and tissue inhibitor of metalloproteinase-1 (TIMP-1) (p <0.01) were elevated, however, hepatic interleukin-10 level was lowered (p <0.05). Both Panax ginseng extract and ginsenoside Rb1 decreased plasma and hepatic triglyceride, hepatic prostaglandin E2, hydroxyproline and TIMP-1 levels, and Panax ginseng extract further inhibited interleukin-1β concentrations (p <0.05).

Conclusions: Panax ginseng extract and ginsenoside Rb1 attenuate plasma aminotransferase activities and liver inflammation to inhibit CCl4-induced liver fibrosis through down-regulation of hepatic prostaglandin E2 and TIMP-1.

Figure 1

The representative histological sections of rat liver specimens. A: hematoxylin and eosin stain at 20 × 10 magnification, B: semi-quantitative scores graded from 0 (no lesion), 1 (trace lesion), 2 (weak lesion), 3 (moderate lesion) to 4 (severe lesion) for fat changes, and from 0 (no lesion), 1 (lesion in the central vein area), 2 (lesion in the central vein area and expansion to the surrounding area) to 3 (lesion in the central and portal vein areas or cirrhosis) for necrosis, inflammation and fibrosis in control, CCl₄, GE and Rb1 groups. Solid and dashed arrows represent the central vein and collagen fibers. Data are presented as mean ± SD (n =10). Values not sharing the same letter differ significantly (p <0.05). Scale bar =50 μm.

Figure 2

The representative histological sections of rat liver specimens. A: Masson’s trichrome stain at 15 × 10 magnification, B: silver stain at 15 × 10 magnification; C: semi-quantitative scores graded from 0 (no collagen formation), 1 (collagen formation in the central vein area), 2 (collagen and fibrous bridge formation in different central vein areas) to 3 (cirrhosis) for fibrosis in the control, CCl₄, GE and Rb1 groups. Collagen fibers stained with Masson’s trichrome appear blue. Reticular fibers stained with silver appear brown. Solid and dashed arrows represent the central vein and fiber bridging. Data are presented as mean ± SD (n =10). Values not sharing the same letter differ significantly (p <0.05). Scale bar =50 μm.

Figure 3

Effects of ginsenosides extract and ginsenoside Rb1 on hepatic lipids in rats. A: hepatic triglycerides, B: total cholesterol concentration. Data are presented as mean ± SD (n =10). Values not sharing the same letter differ significantly (p <0.05).

Figure 4

Effects of ginsenosides extract and ginsenoside Rb1 on liver fibrosis markers in rats. A: hepatic hydroxyproline level, B: MMP-2 level; C: TIMP-1 level. Data are presented as mean ± SD (n =10). Values not sharing the same letter differ significantly (p <0.05).