Swertiamarin or heat-transformed products alleviated APAP-induced hepatotoxicity via modulation of apoptotic and Nrf-2/NF- κ B pathways

獐牙菜苦苷或其热转化产物通过调节细胞凋亡和 Nrf-2/NF- κ B 通路减轻 APAP 诱导的肝毒性

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作者:Qian Zhou, Qixiu Zhou, Rui Xia, Peng Zhang, Yanqing Xie, Zhuya Yang, Afsar Khan, Zhihong Zhou, Wenhong Tan, Lu Liu

Methods

Mice and L-O2 cells were given APAP to establish the hepatotoxicity model in vivo and in vitro. The effects of STM or HTPS on oxidative stress, inflammation, and apoptosis induced by APAP were evaluated, with N-acetylcysteine (NAC) as a positive control.

Objective

Swertiamarin (STM) belongs to iridoid class of compounds, and the heat-transformed products (HTPS) are produced by STM in the process of drug processing. The purpose of this study was to explore the protective effect and mechanism of STM or HTPS on acetaminophen (APAP)-induced hepatotoxicity.

Results

STM or HTPS reduced the APAP-induced apoptosis of L-O2 cells and significantly alleviated the liver injury index induced by APAP (p < 0.01, 0.005) Interestingly, HTPS had better protective effect against APAP-induced hepatotoxicity than STM (p < 0.05). In addition STM or HTPS improved the histological abnormalities; inhibited lipid peroxidation and reduced the level of inflammatory mediators. They also activated the defense system of nuclear factor erythroid 2 related factor 2 (Nrf-2) and inhibited nuclear factor-κ B (NF-κB).

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