Stem-leaf saponins of Panax notoginseng attenuate experimental Parkinson's disease progression in mice by inhibiting microglia-mediated neuroinflammation via P2Y2R/PI3K/AKT/NFκB signaling pathway

Stem-leaf saponins of Panax notoginseng (SLSP) consist of abundant PPD-type saponins possessing a variety of pharmacological properties, however, their function in relation to Parkinson's disease (PD) featuring with microglia-mediated neuroinflammation remains undefined. This study assessed the impact of SLSP on restraining microglia-driven neuroinflammation in experimental models of PD, including 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS) stimulated BV-2 microglia. Our results demonstrated that SLSP inhibited the behavioral impairments and excessive microglial activation in MPTP-treated mice. Furthermore, SLSP was observed to inhibit the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2), and mitigate the phosphorylation of phosphoinositol 3-kinase (PI3K), protein kinase B (AKT), nuclear factor-κB (NFκB) and inhibitor of NFκB protein ɑ (IκBɑ) both in vivo and in vitro. Meanwhile, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α) in BV-2 cells stimulated by LPS. In addition, the P2Y2R agonist partially nullified the inhibitory impacts of SLSP in BV-2 cells treated with LPS. Our results manifested that SLSP inhibited microglia-mediated neuroinflammation in experimental PD models probably through P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP have potential therapeutic benefit for PD by attenuating microglia-mediated neuroinflammation.