Two new constituents from the endophyte of Alternaria alternata and its anti-neuroinflammatory activity guided by...

Two new compounds, 3-hydroxy-1-(3-hydroxy-5-methoxyphenyl)-2-methyl propan-1-one (1) and 1,2,6-trihydroxy-8-methoxy-2,3,3a,9b-tetrahydrocyclopenta[c] isochromen-5(1H)-one (2), along with nine known compounds 3-11, involving pyranones, phenylpropenoids and alkaloids, were obtained from Alternaria alternata, an endophyte isolated from Hypericum perforatum L. The structures were elucidated by extensive spectroscopic analyses, including 1D NMR, 2D NMR, HRESIMS, IR, UV spectroscopy. The absolute configuration was established via spectroscopy techniques and X-ray crystallisation method. Furthermore, guided by molecular docking, compounds 1 and 3 exhibited promising anti-neuroinflammatory activity in LPS-induced BV-2 microglial cells, with IC₅₀ values of 0.9 ± 0.3 μM and 3.0 ± 0.4 μM respectively. Moreover, they effectively attenuated the LPS-induced elevation of NO, TNF-α, IL-6, and IL-1β production in BV-2 microglial cells. These findings diversify the metabolite of A. alternata and highlight their potential as leading compounds against neuroinflammatory-related diseases.