Publication:
Gentiopicroside alleviates neuroinflammation in Parkinson's disease by mediating microglial pyroptosis via the NF-κB/NLRP3/GSDMD pathway

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Date
2025
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Authors
Shen Hong ; Song Hui ; Sun Qiang
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Publisher
Universidad de Murcia, Departamento de Histología e Histopatología
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DOI
https://doi.org/10.14670/HH-18-879
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info:eu-repo/semantics/article
Description
Abstract
Objective. The study aimed to evaluate the therapeutic potential of gentiopicroside (GPS) in Parkinson's disease (PD) through both in vitro and in vivo experiments, focusing on elucidating the underlying mechanisms of its action. Methods. To achieve this, a PD model was established in C57BL6 mice using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), followed by assessment of behavioral changes, pathological alterations, microglial activation, and neuro-inflammation. Simultaneously, a cellular PD model was developed in the BV-2 mouse microglia cell line by exposing them to 1-methyl-4-phenyl-pyridinium (MPP+). The expression of pro-inflammatory molecules was quantified using enzyme-linked immunosorbent assay (ELISA), while pyroptosis was analyzed by flow cytometry with caspase-1/PI double staining. The expression of key factors in the nuclear factor-kappa B (NF-κB)/NOD-like receptor thermal protein domain-associated protein 3 (NLRP3)/gasdermin D (GSDMD) signaling pathway was determined by immunoblotting. Results. The findings revealed that GPS effectively mitigated motor deficits, neurological impairments, microglial activation, and neuroinflammation in the MPTP-induced mouse model of PD. Additionally, GPS protected BV-2 cells from MPP+-induced inflammatory cytokine production and pyroptosis. Mechanistic studies indicated that GPS may exert its neuroprotective effects by inactivating the NF-κB/NLRP3/GSDMD-mediated pyroptotic pathway in both in vivo and in vitro settings. Conclusion. GPS exhibits neuroprotective effects in PD by suppressing microglia-mediated neuro-inflammation and pyroptosis, suggesting its potential as a favorable therapeutic agent for PD treatment
Citation
Histology and Histopathology, Volúmen 40, nº 9 (2025)
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