Madecassoside prevents acute liver failure in LPS/D-GalN-induced mice by inhibiting p38/NF-κB and activating Nrf2/HO-1 signaling

作者：Wang, Wei; Wu, Lingling; Li, Qing; Zhang, Zhuo; Xu, Liba; Lin, Caixia; Gao, Ling; Zhao, Kaili; Liang, Fei; Zhang, Qing; Zhou, Mei; Jiang, Weizhe^*

来源：Biomedicine & Pharmacotherapy, 2018, 103: 1137-1145.

DOI：10.1016/j.biopha.2018.04.162

• Madecassoside
• Lipopolysaccharide/D-galactosamine
• Acute liver failure
• Inflammatory cytokines
• Antioxidants

Madecassoside (MA), a triterpenoid saponin isolated from Centella asiatica, exerts various pharmacological activities including antioxidative and anti-inflammatory effects. The aim of this study was to explore the protective effect of MA in the treatment of lipopolysaccharide (LPS) and D-galactosamine (D-GalN)-induced acute liver failure(ALF) in mice. We hypothesized that MA administration may decrease the degree of liver injury caused by LPS/D-GalN. In this study, we investigated this hypothesis by treating a mouse model of LPS/D-GalN-induced liver injury with MA. Our study demonstrated that MA (20 mg/kg and 40 mg/kg) treatment for 10 days attenuated LPS/D-GalN-induced liver injury by protecting liver function, suppressing the production of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6, and recovering antioxidant enzyme activity. MA also significantly suppressed LPS-stimulated protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 by blocking the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B). In addition, MA treatment enhanced protein levels of heme oxygenase (HO)-1 and anti-oxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) through the upregulation of nuclear factor E2-related factor 2 (Nrf2) in LPS-stimulated liver injury. These results suggest that MA is a promising agent for the treatment of LPS/D-GalN-induced liver injury that could serve as a candidate for the development of a hepatoprotective drug against ALF.

• 出版日期2018-7
• 单位广西医科大学