Anti-Neuroinflammatory Activity of New Naturally Occurring Benzylated Hydroxyacetophenone Analogs from the Endophytic Fungus Alternaria sp. J030.

Chemical studies on the culture broth of the endophytic fungus Alternaria sp. J030 led to the identification of three benzylated hydroxyacetophenone derivatives, bauvaroalterins A-C (1-3), and 34 structurally diverse metabolites (4-37). The new structures were elucidated by extensive spectroscopic analyses including UV, IR, 1D and 2D NMR, HR-ESI-MS, and further confirmed using single crystal X-ray diffraction. The in vitro anti-neuroinflammatory effects of the co-isolated metabolites were evaluated in lipopolysaccharide (LPS)-stimulated microglial cells. Compounds 1-3 were shown to significantly reduce LPS-induced NO production by inhibiting the expression of iNOS, as well as inhibiting LPS-induced production of the inflammatory factors TNF-α, IL-1β and IL-6. Further studies revealed that 1-3 were capable of down-regulating the expression of NF-κB subunits p50 and p65, thereby suppressing the activation of NF-κB by inhibiting the LPS-induced phosphorylation of IκB-α. Together these findings demonstrate that bauvaroalterins A-C (1-3) exert anti-neuroinflammatory effects via inhibition of the NF-κB/iNOS signalling pathway in LPS induced BV-2 cells.