Protective effect of Curcuma longa L. extract on CCl4-induced acute hepatic stress

Abstract

Background: The Curcuma longa L. (CLL) rhizome has long been used to treat patients with hepatic dysfunction. CLL is a member of the ginger family of spices that are widely used in China, India, and Japan, and is a common spice, coloring, flavoring, and traditional medicine. This study was performed to evaluate the hepatoprotective activity of CLL extract and its active component curcumin in an acute carbon tetrachloride (CCl₄)-induced liver stress model.

Methods: Acute hepatic stress was induced by a single intraperitoneal injection of CCl₄ (0.1 ml/kg body weight) in rats. CLL extract was administered once a day for 3 days at three dose levels (100, 200, and 300 mg/kg/day) and curcumin was administered once a day at the 200 mg/kg/day. We performed alanine transaminase (ALT) and aspartate transaminase (AST). activity analysis and also measured total lipid, triglyceride, and cholesterol levels, and lipid peroxidation.

Results: At 100 g CLL, the curcuminoid components curcumin (901.63 ± 5.37 mg/100 g), bis-demethoxycurcumin (108.28 ± 2.89 mg/100 g), and demethoxycurcumin (234.85 ± 1.85 mg/100 g) were quantified through high liquid chromatography analysis. In CCl₄-treated rats, serum AST and ALT levels increased 2.1- and 1.2-fold compared with the control. AST but not ALT elevation induced by CCl₄ was significantly alleviated in CLL- and curcumin-treated rats. Peroxidation of membrane lipids in the liver was significantly prevented by CLL (100, 200, and 300 mg/kg/day) on tissue lipid peroxidation assay and immunostaining with anti-4HNE antibody. We found that CLL extract and curcumin exhibited significant protection against liver injury by improving hepatic superoxide dismutase (p < 0.05) and glutathione peroxidase activity, and glutathione content in the CCl₄-treated group (p < 0.05), leading to a reduced lipid peroxidase level.

Conclusion: Our data suggested that CLL extract and curcumin protect the liver from acute CCl₄-induced injury in a rodent model by suppressing hepatic oxidative stress. Therefore, CLL extract and curcumin are potential therapeutic antioxidant agents against acute hepatotoxicity.

Keywords: CLL extract; Curcumin; GSH; Hepatotoxicity; Lipid peroxidation.

Fig. 1

HPLC analysis of CLL extract. a Chemical structure of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC). b HPLC chromatogram analysis of CLL extract

Fig. 2

Effects of CLL extract on serum liver biomarkers. Serum AST (a) and ALT (b) were analyzed in control, 0.1 ml/kg CCl₄, CCl₄ with curcumin, CCl₄ with CLL extract (100, 200, or 300 mg/kg), 200 mg/kg curcumin alone, and 300 mg/kg CLL extract alone groups. Each bar represents the mean value of experiments performed in triplicate ± S.E.M. (n = 10). *p < 0.05 compared with the CCl₄ group

Fig. 3

Effects of CLL extract on SOD and GPx activity. a Hepatic SOD and b GPx activity was analyzed in control, 0.1 ml/kg CCl₄, CCl₄ with curcumin, CCl₄ with CLL extract (100, 200, or 300 mg/kg), 200 mg/kg curcumin alone, and 300 mg/kg CLL extract alone groups. Each bar represents the mean value of experiments performed in triplicate ± S.E.M. (n = 10). *p < 0.05 compared with the CCl₄ group

Fig. 4

Effects of CLL extract on hepatic lipid peroxidation. The formation of a malondialdehyde (MDA) and b 4-HNE was analyzed in control, 0.1 ml/kg CCl₄, CCl₄ with 200 mg/kg curcumin, CCl₄ with CLL extract (100, 200, or 300 mg/kg), 200 mg/kg curcumin, and 300 mg/kg CLL extract groups. Each bar represents the mean value of experiments performed in triplicate ± S.E.M. (n = 10). *p < 0.05 compared with the CCl₄ group

Fig. 5

Effects of CLL extract on hepatic redox capacity. a Reduced glutathione (GSH), b total GSH, c GSH/oxidized glutathione (GSSG) ratio and d GSH+GSSG content were analyzed in control, 0.1 ml/kg CCl₄, CCl₄ with 200 mg/kg curcumin, CCl₄ with CLL extract (100, 200, or 300 mg/kg), 200 mg/kg curcumin, and 300 mg/kg CLL extract groups. Each bar represents the mean value of experiments performed in triplicate ± S.E.M. (n = 10). *p < 0.05 compared with the CCl₄ group