Five brasilane-type sesquiterpenoids with neuroprotective activities from Xylaria nigripes

Five brasilane-type sesquiterpenoids, including four previously undescribed compounds named xylaribrasilaids A-D, along with a known analogue, were isolated from the ethyl acetate extracts of solid fermentation from Xylaria nigripes. X. nigripes, a traditional Chinese medicinal fungus utilized for treating various ailments such as insomnia, trauma, and depression, has garnered attention due to its pharmacological potential. Their structures and absolute configurations were elucidated through comprehensive spectroscopic analysis, including NMR, HRESIMS, and experimental ECD data. In vitro bioassays were conducted to assess the neuroprotective activities of these compounds against glutamate-induced damage in PC12 cells. Remarkably, all isolated compounds demonstrated significant enhancements in cell viability while concurrently inhibiting apoptosis. Moreover, they effectively attenuated oxidative stress markers, as evidenced by increased activities of superoxide dismutase and glutathione. Furthermore, these compounds displayed the capacity to mitigate intracellular reactive oxygen species accumulation, highlighting their potential in combating oxidative stress-related neurodegenerative disorders.