Nrf2-Dependent Protective Effect of Paeoniflorin on α-Naphthalene Isothiocyanate-Induced Hepatic Injury

作者：Liuliu Mao, Jun Chen, Kang Cheng, Zhihua Dou, Jonathan D. Leavenworth, Hengyue Yang, Diyuan Xu, Lin Luo · 发表于：The American Journal of Chinese Medicine · 年份：2022 · DOI：10.1142/s0192415x22500562 · 被引用次数：15 · 研究领域：Drug-Induced Hepatotoxicity and Protection、Genomics, phytochemicals, and oxidative stress、Drug Transport and Resistance Mechanisms

The pathological mechanism of cholestatic hepatic injury is associated with oxidative stress, hepatocyte inflammation, and dysregulation of hepatocyte transporters. Paeonia lactiflora Pall. and its compound can improve hepatic microcirculation, dilate bile duct, and promote bile flow, which is advantageous to ameliorate liver damage. Paeoniflorin (PEA), as the main efficacy component of Paeonia lactiflora Pall., has multiple pharmacological effects. PEA improves liver injury, but it remains obscure whether the protective action on [Formula: see text]-naphthalene isothiocyanate (ANIT)-induced cholestatic liver injury is dependent on the NF-E2 p45-related Factor 2 (Nrf2) signaling pathway. In this study, C57BL/6 mice were administrated with 80 mg⋅kg[Formula: see text]⋅d[Formula: see text] ANIT followed by PEA (75, 150, and 300 mg⋅kg[Formula: see text]⋅d[Formula: see text]) orally for 10 days, respectively. Tissue histology and liver function were detected, including serum enzymes, gallbladder (GB) weight, phenobarbital-induced sleeping time (PEN-induced ST), hepatic uridine di-phosphoglucuronosyltransferase (UDPG-T), malondialdehyde (MDA), and glutathione (GSH). The expressions of protein Nrf2, sodium taurocholate cotransporting polypeptide (Ntcp), and NADPH oxidase 4 (Nox4) were evaluated. Nrf2 plasmid or siRNA-Nrf2 transfection on LO2 cells and Nrf2 −/− mice were used to explore the liver protective mechanism of PEA. Compared to ANIT-treated mice, PEA decreased serum levels o...