Polysaccharide extract PCP1 from Polygonatum cyrtonema ameliorates cerebral ischemia-reperfusion injury in rats by inhibiting TLR4/NLRP3 pathway.
10.19540/j.cnki.cjcmm.20250116.401
- Author:
Xin ZHAN
1
;
Zi-Xu LI
1
;
Zhu YANG
1
;
Jie YU
1
;
Wen CAO
1
;
Zhen-Dong WU
2
;
Jiang-Ping WU
3
;
Qiu-Yue LYU
3
;
Hui CHE
1
;
Guo-Dong WANG
1
;
Jun HAN
4
Author Information
1. Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of Institute of Health and Medicine,Wannan Medical College Wuhu 241002,China Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicine in Southern Wuhu 241002,China Anhui Innovative Center for Drug Basic Research of Metabolic Diseases Wuhu 241002,China.
2. Anhui Qingyang Jiuhua Traditional Chinese Medicine Technology Qingyang 242800,China.
3. Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of Institute of Health and Medicine,Wannan Medical College Wuhu 241002,China Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicine in Southern Wuhu 241002,China Anhui Innovative Center for Drug Basic Research of Metabolic Diseases Wuhu 241002,China Wuhu Modern Technology Research and Development Center of Chinese Herbal Medicine and Functional Food Wuhu 241002,China.
4. Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of Institute of Health and Medicine,Wannan Medical College Wuhu 241002,China Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicine in Southern Wuhu 241002,China Anhui Innovative Center for Drug Basic Research of Metabolic Diseases Wuhu 241002,China Wuhu Modern Technology Research and Development Center of Chinese Herbal Medicine and Functional Food Wuhu 241002,China Anhui College of Traditional Chinese Medicine Wuhu 241002,China.
- Publication Type:Journal Article
- Keywords:
PCP1;
Toll-like receptor 4;
cerebral ischemia-reperfusion injury;
inflammation;
pyroptosis
- MeSH:
Animals;
Toll-Like Receptor 4/genetics*;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*;
Rats, Sprague-Dawley;
Rats;
Reperfusion Injury/genetics*;
Male;
Signal Transduction/drug effects*;
Polysaccharides/isolation & purification*;
Polygonatum/chemistry*;
Brain Ischemia/genetics*;
Drugs, Chinese Herbal/administration & dosage*;
Mice;
Humans
- From:
China Journal of Chinese Materia Medica
2025;50(9):2450-2460
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
