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.
10.1016/S1875-5364(25)60809-0
- Author:
Hui WU
1
;
Chenyang NI
2
;
Yu ZHANG
2
;
Yingying SONG
2
;
Longchan LIU
2
;
Fei HUANG
3
;
Hailian SHI
2
;
Zhengtao WANG
2
;
Xiaojun WU
4
,
5
Author Information
1. Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: zgykdxwuhui@foxmail.com.
2. Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
3. Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: Fei_H@hotmail.com.
4. Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, The MOE Innovation Centre for Basic Medicine Research on Qi-Blood TCM Theories, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: xiaojunwu320@
5. com.
- Publication Type:Journal Article
- Keywords:
Microglia;
NFκB;
Neuroinflammation;
P2Y2 receptor;
Stem-leaf saponins of Panax Notoginseng
- MeSH:
Animals;
Panax notoginseng/chemistry*;
Saponins/pharmacology*;
Microglia/immunology*;
Mice;
NF-kappa B/immunology*;
Signal Transduction/drug effects*;
Proto-Oncogene Proteins c-akt/immunology*;
Phosphatidylinositol 3-Kinases/genetics*;
Male;
Parkinson Disease/immunology*;
Mice, Inbred C57BL;
Disease Models, Animal;
Plant Leaves/chemistry*;
Neuroinflammatory Diseases/drug therapy*;
Humans
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(1):43-53
- CountryChina
- Language:English
-
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 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 (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (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-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 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.
