Anti-Neuroinflammatory Effect of Alkaloid-Enriched Extracts from Huperzia Serrata (Thunb.) Trevis in Lipopolysaccharide-Stimulated Bv2 Microglia Cells

Abstract

Introduction: Overactivated microglia are a chronic source of meaningful neurotoxic factors, and the inhibition of microglial overactivation restores neuronal survival. Therefore, downregulation of microglial activation may possibly slow or delay the progression of neurodegenerative disorders. Huperzia serrata (Thunb.) Trevis has been widely used to treat chronic diseases involving neuromuscular and cardiovascular diseases. However, the anti-neuroinflammatory effects of the alkaloid-enriched extracts of H. serrata (HsAE) have not yet been investigated. This study was performed to determine the anti-neuroinflammatory effect of HsAE in LPS-stimulated BV2 microglial cells and to investigate the underlying mechanisms.Methods: Arrays of techniques including MTT assay, western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were used to track the pro-inflammatory signaling pathway under HsAE treatment in lipopolysaccharide (LPS)-stimulated BV2 cells.Results: HsAE is non-toxic to BV-2 cells and can even rescue lethal cells upon LPS treatment. HsAE treatment reduced nitric oxide production, cytokine secretion, and inflammation-related pathways (i.e., COX-2, iNOS, and MAPK pathways). Intriguingly, the comparison of the efficacy of HsAE between pre- and post-LPS induction revealed that this traditional medicine is highly effective. Our results therefore support the prophylactic effect of HsAE on LPS-induced neuroinflammation in BV2 cells. Moreover, HsAE prevented activated microglia-induced neurotoxicity in N2a neuronal cells. Conclusion: These results represent a milestone for the development of alkaloid-enriched extracts of H. serrata as a potential candidate for the treatment of neurodegenerative diseases based on herbal medicine. Further in vivo studies to investigate the efficacy of HsAE as an anti-neuroinflammatory agent will be necessary for future applications.

Keywords: Alkaloid-enriched extract of Huperzia serrata (Thunb.) Trevis, Anti-neuroinflammatory, Microglia, Lipopolysaccharide, BV2 cells