Hepatoprotective Effect of Polyphenol‐Enriched Fraction from Folium Microcos on Oxidative Stress and Apoptosis in Acetaminophen‐Induced Liver Injury in Mice

Folium Microcos (FM), the leaves of Microcos paniculata L., shows various biological functions including antioxidant activity and α ‐glucosidase inhibitory effect. However, its therapeutic potential in acute liver injury is still unknown. This study investigated the hepatoprotective effect and underlying mechanisms of the polyphenol‐enriched fraction (FMF) from Folium Microcos . FMF exhibited strong free radical scavenging activities and prevented HepG2/Hepa1–6 cells from hydrogen peroxide‐ (H 2 O 2 ‐) induced ROS production and apoptosis in vitro. Antioxidant activity and cytoprotective effects were further verified by alleviating APAP‐induced hepatotoxicity in mice. Western blot analysis revealed that FMF pretreatment significantly abrogated APAP‐mediated phosphorylation of MAPKs, activation of proapoptotic protein caspase‐3/9 and Bax, and restored expression of antiapoptotic protein Bcl2. APAP‐intoxicated mice pretreated with FMF showed increased nuclear accumulation of nuclear factor erythroid 2‐related factor (Nrf2) and elevated hepatic expression of its target genes, NAD(P)H:quinine oxidoreductase 1 (NQO1) and hemeoxygenase‐1(HO‐1). HPLC analysis revealed the four predominantly phenolic compounds present in FMF: narcissin, isorhamnetin‐3‐O‐ β ‐D‐glucoside, isovitexin, and vitexin. Consequently, these findings indicate that FMF possesses a hepatoprotective effect against APAP‐induced hepatotoxicity mainly through dual modification of ROS/MAPKs/apoptosis axis and Nrf2‐mediated antioxidant response, which may be attributed to the strong antioxidant activity of phenolic components.