Protective effects of a traditional Chinese herbal formula Jiang-Xian HuGan on Concanavalin A-induced mouse hepatitis via NF-kappa B and Nrf2 signaling pathways
作者 Tang, Huan-Huan; Li, Hai-Long; Li, Yue-Xuan; You, Yan; Guan, Yun-Yun; Zhang, Su-Lin; Liu, Li-Xin; Bao, Wei-Lian; Zhou, Yong; Shen, Xiao-Yan
期刊 JOURNAL OF ETHNOPHARMACOLOGY , MAY 10 2018,:217
摘要
Ethnopharmacological relevance: Jiang-Xian HuGan (JXHG) formulated by five natural products including Freshwater clam (Corbicula fluminea), Curcuma longa L, Ligustrtun lucidum, Eclipta prostrate (L) L and Paeonia lactiflora Pall, has exhibited a great hepatoprotective effect. Aim of this study: We investigated the effect of JXHG on concanavalin A (ConA)-induced acute live injury in mice, and to elucidate its underlying molecular mechanisms.Materials and methods: Jiangkanling Capsule (900 mg/kg), low-dose JXHG (LJXHG, 700 mg/kg), high-dose JXHG (HJXHG, 1400 mg/kg) were administered to mice by oral gavage daily for 20 days prior to a single intravenous injection of ConA (20 mg/kg). Liver injury was evaluated by measuring the serum levels of enzymes and cytokines as well as liver histological analysis. We also measured the hepatic expression of cytokines at mRNA levels and the proteins related to NF-kappa B and Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathways.Result Our results showed that JXHG pretreatment significantly alleviated ConA-induced live injury as evidenced by decreased serum levels of glutamic-pyruvic transaminase (ALT) and glutamic oxalacetic transaminase (AST), and reduced hepatocyte apoptosis and mortality. Furthermore, JXHG was able to significantly reduce the serum levels of proinflammatory cytokines, down-regulate the mRNA expression of interleukin-6 (IL-6) and interferon-gamma (IFN-gamma), and up-regulate IL-10 as well as superoxide-dimutase-1 (SOD1), glutathione reductase (GSR) and Glutathione peroxidase 2 (GPX2) mRNA in the liver tissues after Con A injection. In addition, JXHG pretreatment dramatically suppressed the phosphorylation of NF-kappa B p65 (p65), increased Nrf2 expression, and decreased the expression ratio of cleaved caspase-3/caspase-3 in liver tissues.Conclusion: These results suggest that JXHG protects against ConA-induced acute live injury through inhibiting NF-kappa B mediated inflammatory pathway and promoting Nrf2 mediated anti-oxidative stress signaling pathway.