Neuroprotective effects of a new triterpenoid from edible mushroom on oxidative stress and apoptosis through the BDNF/TrkB/ERK/CREB and Nrf2 signaling pathway in vitro and in vivo

Inonotus obliquus (Fr.) Pilat is an edible mushroom which is used to produce tea and syrup due to its medicinal properties. In this study, 10 secondary metabolites (1-10), including a new lanostane triterpenoid named 2 alpha-hydroxy-inotodiol (2 alpha-HI, 1), were identified from the edible mushroom I. obliquus through high-resolution electrospray ionization mass spectrometry (HRESIMS) and nuclear magnetic resonance spectroscopy (NMR) data analysis. The neuroprotective function of all steroidal metabolites in H2O2-induced SH-SY5Y cells was investigated. The results showed that 2 alpha-HI exhibited the most remarkable neuroprotective activity. In the meantime, 2 alpha-HI significantly ameliorated oxidative stress damage, reactive oxygen species (ROS) accumulation and mitochondrial damage induced by H2O2 in SH-SY5Y cells. The Nrf2 siRNA and inhibitors transfected the SH-SY5Y cells, indicating the Nrf2 and BDNF/TrkB/ERK/CREB pathway mediated the neuroprotective effects of 2 alpha-HI against the H2O2-stimulated oxidative stress and apoptosis. Moreover, the neuroprotection of 2 alpha-HI was preliminarily verified in zebrafish. In conclusion, this research was the first to confirm that 2 alpha-HI could effectively protect SH-SY5Y cells against H2O2-induced oxidative stress and apoptosis via the Nrf2 and BDNF/TrkB/ERK/CREB signaling pathway. Hence, this mushroom could be a potential dietary supplement to ameliorate neurodegenerative diseases.

Automated summary

This study identified 10 secondary metabolites, including a new lanostane triterpenoid named 2 alpha-hydroxy-inotodiol (2 alpha-HI), from the edible mushroom I. obliquus. The results showed that 2 alpha-HI exhibited remarkable neuroprotective activity against oxidative stress and apoptosis induced by H2O2 in SH-SY5Y cells, mediated by the Nrf2 and BDNF/TrkB/ERK/CREB signaling pathway. Additionally, the neuroprotective effects of 2 alpha-HI were preliminarily verified in zebrafish.