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 neuroinf...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 evaluated 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 mitigated behavioral impairments and excessive microglial activation in models of PD,including MPTP-treated mice.Additionally,SLSP inhibited the upregulation of inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX2)and attenuated the phosphorylation of PI3K,protein kinase B(AKT),nuclear factor-κB(NFκB),and inhibitor of NFκB proteinα(IκBα)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-2cells.Notably,the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPStreated BV-2 cells.These results suggest that SLSP inhibit microglia-mediated neuroinflammation 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 attenuating microglia-mediated neuroinflammation.展开更多
Neural stem/progenitor cells：Radial glial cells constitute multipotent cells in the ventricular zone,lining the wall of the lateral ventricle of the embryonic brain.They have the capacity to give rise to cells belong...Neural stem/progenitor cells：Radial glial cells constitute multipotent cells in the ventricular zone,lining the wall of the lateral ventricle of the embryonic brain.They have the capacity to give rise to cells belonging to all three major linages（neurons,astrocytes and oligodendrocytes）of the nervous system（Tang and Illes,2017）.展开更多
基金supported by the Educational Commission of Shanghai in China(No.2021LK114)the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(No.2023YZZ02)the Xinglin Young Talent Program at Shanghai University of Traditional Chinese Medicine(No.A1-U17205010430)。
文摘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 evaluated 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 mitigated behavioral impairments and excessive microglial activation in models of PD,including MPTP-treated mice.Additionally,SLSP inhibited the upregulation of inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX2)and attenuated the phosphorylation of PI3K,protein kinase B(AKT),nuclear factor-κB(NFκB),and inhibitor of NFκB proteinα(IκBα)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-2cells.Notably,the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPStreated BV-2 cells.These results suggest that SLSP inhibit microglia-mediated neuroinflammation 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 attenuating microglia-mediated neuroinflammation.
基金supported by Deutsche Forschungsgemeinschaft(DFGIL 20/21-1)Sino-German Centre(GZ919)
文摘Neural stem/progenitor cells：Radial glial cells constitute multipotent cells in the ventricular zone,lining the wall of the lateral ventricle of the embryonic brain.They have the capacity to give rise to cells belonging to all three major linages（neurons,astrocytes and oligodendrocytes）of the nervous system（Tang and Illes,2017）.
