Synergistic hepatoprotective effects of CGplus on CCl4-induced acute injury.

Abstract

Traditional Chinese/Korean medicine suggests "blood stasis ()", "stagnation of vital energy ()" and "dampness and Phlegm ()" as the main etiologies of liver disorders, and multiherbal formulas are generally believed to exert synergistic action. The present study aimed to investigate the synergistic hepatoprotective effects of CGplus (a mixture of Salviae miltiorrhiza, Artemisia iwayomogi and Ammomum xanthioides) compared to those of the individual herbs. A total of fifty-six male Balb/C mice were randomly divided into eight groups and were administered water (normal and CCl4 groups), 100mg/kg S. miltiorrhiza, A. iwayomogi, or A. xanthioides, 50 or 100mg/kg CGPlus or dimethyl dimethoxybiphenyl dicarboxylate (DDB) as a positive control for 4 consecutive days. After a single CCl4 injection (i.p., 10mL/kg of 0.2% CCl4 in olive oil), blood and liver tissues were collected after 18h of fasting for serum biochemistry, histopathological examination and molecular analyses. CCl4 injection induced drastic hepatic injury characterized by a more than 30-fold increase in the release of AST and ALT into the serum. These alterations were significantly attenuated by pretreatment with each of the three herbs, while the effects of the individual herbs were synergistically augmented by CGPlus pretreatment. The synergistic hepatoprotective actions of CGPlus were demonstrated consistently by analyses of oxidative stress (oxidative stressors, oxidation products and antioxidant enzymes), pro-/anti-inflammatory cytokines (TNF-ɑ, IL-1β, IL-6, IL-10), and apoptosis (caspase-3, p53 and BAX) and histopathology. These data suggest that CGPlus exerts its hepatoprotective effects in a synergistic manner, and further studies are required for clinical application using other chronic models.