Effect and mechanisms of curcumin and/or saikosaponin a on the inhibition of CCl4-induced liver injury in rats

• Main Authors: Shu-Ju Wu, 吳淑如
• Other Authors: 趙振瑞
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/79958952583112409238

博士 === 臺北醫學大學 === 藥學系(博士班) === 98 === Curcumin and saikosaponin a, as the antioxidants, are bioactive phytochemicals of turmeric and Bupleurum. The combined effect of curcumin and saikosaponin a on hepatoprotection against CCl4-induced liver injury has not been studied yet. Therefore, we used pure phytochemical compounds of curcumin and saikosaponin a to determine their hepatoprotective effects on CCl4-induced liver injury. This study investigated the effects of supplementation with curcumin and/or saikosaponin a on carbon tetrachloride (CCl4)-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into 5 groups: control, CCl4, CCl4+curcumin (0.005%; CU), CCl4+ saikosaponin a (0.004%; SS), and CCl4+curcumin+saikosaponin a (0.005%+0.004%; CU+SS) groups. CCl4 (40% in olive oil) was injected intraperitoneally at a dose of 0.75 mL/kg body weight once a week. Curcumin and/or saikosaponin a was administered orally 1 week before CCl4 injection for 8 weeks. Rats were intraperitoneally injected with an equivalent dosage of olive oil as the control group. After 8-week treatments with curcumin and/or saikosaponin a, plasma and liver were collected for biochemical and pathological analyses. The pathological results showed that curcumin and saikosaponon a reduced fatty change and hepatic necrosis in the portal veins, and the effect of the CU+SS group was more obvious (P <0.05). Liver fibrosis was ameliorated in the SS and CU+SS groups. Hstopathological results showed hepatic collagen deposition was significantly reduced in the CU and SS groups, and activated nuclear factor-?羠 expression induced by CCl4 in the liver was significantly inhibited by curcumin and/or saikosaponin a. After 8 weeks, supplementation with curcumin and/or saikosaponin a significantly decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, as well as plasma and hepatic cholesterol and triglyceride levels. Supplementation with curcumin and/or saikosaponin a significantly improved hepatic antioxidant status and suppressed malondialdehyde formation. The CU+SS group showed increases in hepatic superoxide dismutase activity and total glutathione level compared with the CCl4 group. Hepatic proinflammatory cytokines tumor necrosis factor-?? (TNF-α), interleukin-1?? (IL-1β), and interleukin-6 (IL-6) were significantly decreased, and the anti-inflammatory cytokine interleukin-10 (IL-10) was significantly increased by supplementation with curcumin and/or saikosaponin a. Additionally, curcumin and/or saikosaponin a significantly decreased hepatic transforming growth factor-??1 (TGF-??1) and hydroxyproline levels. Therefore, supplementation with curcumin and/or saikosaponin a protects against CCl4 –induced liver injury and fibrosis by attenuating hepatic lipids and lipid peroxidation, enhancing antioxidant defense, and suppressing inflammation and fibrogenesis. However, Curcumin and saikosaponin a had no additive effects on hepatoprotection.