Terpenoids from stigma maydis (Zea mays L.) alleviate hydrogen peroxide-induced SH-SY5Y cell injury by activating Nrf2

Five terpenoids (1-5), including three new ent-kaurane diterpenoids (1-3), one new ent-rosane type diterpenoid (4) and one known triterpenoid (5), were isolated from stigma maydis (Zea mays L.). The structures of the compounds were elucidated by comprehensive spectroscopic analyses. The relative configurations of stigmanes A-D (1-4) were determined by NOESY experiments. In addition, the relative configuration of stigmane D (4) was further established by NMR calculations. The absolute configurations of these compounds were identified by a comparison of experimental and calculated specific rotations. The neuroprotective effects of these compounds against H₂O₂-induced injury in human neuroblastoma SH-SY5Y cells were evaluated, and the results showed that among the compounds, 2 exhibited the most significant neuroprotection. Further study demonstrated that 2 could activate nuclear factor E2-related factor (Nrf2), downregulate apoptosis and reactive oxygen species (ROS) generation, and increase antioxidant enzyme activities in SH-SY5Y cells. However, the neuroprotective effect was reversed when Nrf2 was silenced. In conclusion, this study suggested that terpenoids from stigma maydis exerted neuroprotective effects through Nrf2 activation.

Keywords: Neuroprotection; Nrf2; Stigma maydis; Terpenoids.