獐牙菜苦苷或热转化产物通过调节凋亡和Nrf-2/NF-κB信号通路减轻对乙酰氨基酚诱导的肝毒性。

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

作者信息

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

机构信息

Yunnan Yunzhong Institute of Nutrition and Health, Yunnan University of Chinese Medicine, Kunming 650500, People's Republic of China.

Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.

出版信息

Heliyon. 2023 Jul 27;9(8):e18746. doi: 10.1016/j.heliyon.2023.e18746. eCollection 2023 Aug.

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.

METHODS

Mice and L-O2 cells were given APAP to establish the hepatotoxicity model and . 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.

RESULTS

STM or HTPS reduced the APAP-induced apoptosis of L-O2 cells and significantly alleviated the liver injury index induced by APAP ( < 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-B).

目的

獐牙菜苦苷（STM）属于环烯醚萜类化合物，其热转化产物（HTPS）是在药物炮制过程中由STM产生的。本研究旨在探讨STM或HTPS对乙酰氨基酚（APAP）诱导的肝毒性的保护作用及其机制。

方法

给小鼠和L-O2细胞给予APAP以建立肝毒性模型。以N-乙酰半胱氨酸（NAC）作为阳性对照，评估STM或HTPS对APAP诱导的氧化应激、炎症和细胞凋亡的影响。

结果

STM或HTPS减少了APAP诱导的L-O2细胞凋亡，并显著减轻了APAP诱导的肝损伤指数（P<0.01，0.005）。有趣的是，HTPS对APAP诱导的肝毒性的保护作用比STM更好（P<0.05）。此外，STM或HTPS改善了组织学异常；抑制了脂质过氧化并降低了炎症介质水平。它们还激活了核因子红细胞2相关因子2（Nrf-2）的防御系统并抑制了核因子-κB（NF-κB）。