Abstract
Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinflammation,remains unclear.This study evalu-ated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models,including the 1-methyl-4-phenylpyridinium(MPTP)-induced mouse model and lipopolysaccharide(LPS)-stimulated BV-2 microglia.Our findings revealed that SLSP mitig-ated behavioral impairments and excessive microglial activation in models of PD,including MPTP-treated mice.Additionally,SLSP inhibited the upregulation of inducible nitric oxide synthase(iNOS)and cyclooxygenase-2(COX2)and attenuated the phosphorylation of PI3K,protein kinase B(AKT),nuclear factor-KB(NFKB),and inhibitor of NFκB protein α(IKBα)both in vivo and in vitro.Moreover,SLSP suppressed the production of inflammatory markers such as interleukin(IL)-1β,IL-6,and tumor necrosis factor alpha(TNF-α)in LPS-stimulated BV-2 cells.Notably,the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells.These results suggest that SLSP inhibit microglia-mediated neuroinflam-mation in experimental PD models,likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway.These novel findings indicate that SLSP may offer therapeutic potential for PD by at-tenuating microglia-mediated neuroinflammation.
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