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

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 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. Results: STM or HTPS reduced the APAP-induced apoptosis of L-O2 cells and significantly alle viated 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-kappa B (NF-kappa B).

Automated summary

This study aimed to explore the protective effect and mechanism of swertiamarin (STM) or its heat-transformed products (HTPS) on acetaminophen (APAP)-induced hepatotoxicity. The results showed that STM or HTPS could reduce APAP-induced apoptosis of L-O2 cells and markedly alleviate the liver injury induced by APAP. Interestingly, HTPS exhibited a better protective effect against APAP-induced hepatotoxicity than STM. Furthermore, STM or HTPS improved histological abnormalities, inhibited lipid peroxidation, reduced the level of inflammatory mediators, and modulated the defense system of Nrf-2 and NF-kappa B.