| Summary: | Seven new withanolides (1−7) and four known ones (8−11) were isolated from the calyxes and fruits of Nicandra physaloides, an edible and medicinal plant. Their structures were identified by extensive spectroscopic analyses or comparison with literature data. The antioxidant effects and hepatoprotective mechanisms of compounds 1–11 on hydrogen peroxide (H2O2)-induced oxidative stress injury were investigated. Among them, compound 11 showed significant activity with EC50 value of 83.78 ± 0.30 μM. Further, 11 was found to markedly increase cellular survivals and activities of SOD, CAT and GSH, and to reduce the accumulation of reactive oxygen species (ROS) in H2O2-induced LO2 cells. In addition, compound 11 significantly activated Nrf2 nuclear translocation and enhanced the expression of target gene HO-1, suggesting its preliminary mechanism of protective effects. In summary, withanolide 11 might be used as a lead compound for developing a hepatopathy medicine owing to its antioxidative and hepatoprotective effects.
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