Detoxification effects and potential mechanisms of NP-induced hepatotoxicity by ethanolic extracts from Clinacanthus nutans (Burm.f.) Lindau leaf

Abstract Clinacanthus nutans (Burm.f.) Lindau (C. nutans) is native to tropical Asian countries and is an important ingredient in the traditional medicinal system. It is of interest because of the flavonoids it contains, which are rare in plants. It has traditionally been used to treat herpes infections and snake venoms. However, the ability of C. nutans to counteract exogenous chemical-induced hepatotoxicity is not yet known. Nonylphenol (NP) is a widely distributed environmental endocrine disruptor, and the liver is one of the target organs for its toxic effects. In this study, we designed in vitro tests to investigate the protective effect of ethanolic extracts from C. nutans leaf (CE) on NP-induced hepatotoxicity and its molecular mechanism. Sixty µM NP was selected as the optimum to treat Hep G2 cells for 24 h to establish a cell injury model, and the intervention doses of CE were 0.25, 0.5, 1, 2 mg/mL, followed by ERK inhibitor (PD98059), P38 inhibitor (SB202190), Nrf2 inhibitor (ML385) to assist in validation of the intervention mechanism. The results showed that CE could reverse NP-induced Hep G2 cytotoxicity and upregulated cell survival, cellular GSH content, CAT viability and ATP content which was probably achieved by inhibiting ERK/P38 mitogen-activated protein kinases (MAPKs) pathway and activating the nuclear erythroid 2-related factor 2/Heme Oxygenase-1 (Nrf2/HO-1) pathway. These data suggest that CE play a detoxifying role in NP-induced hepatotoxicity, which may be achieved by inhibiting the ERK/P38 MAPKs pathway and activating the Nrf2/HO-1 pathway.