Shen Hong, Song Hui, Sun Qiang
Department of Encephalopathy, Suzhou Wujiang District Hospital of Traditional Chinese Medicine (Suzhou Wujiang District Second People's Hospital), Suzhou, Jiangsu Province, PR China.
Department of Neurology, TaiHe Hospital, Hubei University of Medicine, Shiyan, Hubei Province, PR China.
Histol Histopathol. 2025 Sep;40(9):1467-1478. doi: 10.14670/HH-18-879. Epub 2025 Jan 27.
The study aimed to evaluate the therapeutic potential of gentiopicroside (GPS) in Parkinson's disease (PD) through both and experiments, focusing on elucidating the underlying mechanisms of its action.
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 neuroinflammation. 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.
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 and settings.
GPS exhibits neuroprotective effects in PD by suppressing microglia-mediated neuroinflammation and pyroptosis, suggesting its potential as a favorable therapeutic agent for PD treatment.
本研究旨在通过体内和体外实验评估龙胆苦苷（GPS）在帕金森病（PD）中的治疗潜力，重点阐明其作用的潜在机制。
为此，使用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）在C57BL6小鼠中建立PD模型，随后评估行为变化、病理改变、小胶质细胞活化和神经炎症。同时，通过将BV-2小鼠小胶质细胞系暴露于1-甲基-4-苯基吡啶离子（MPP）来建立细胞PD模型。使用酶联免疫吸附测定（ELISA）定量促炎分子的表达，同时通过半胱天冬酶-1/碘化丙啶（PI）双重染色的流式细胞术分析细胞焦亡。通过免疫印迹法测定核因子-κB（NF-κB）/NOD样受体热蛋白结构域相关蛋白3（NLRP3）/gasdermin D（GSDMD）信号通路中关键因子的表达。
研究结果表明，GPS可有效减轻MPTP诱导的PD小鼠模型中的运动缺陷、神经损伤、小胶质细胞活化和神经炎症。此外，GPS保护BV-2细胞免受MPP诱导的炎性细胞因子产生和细胞焦亡。机制研究表明，GPS可能通过在体内和体外环境中使NF-κB/NLRP3/GSDMD介导的细胞焦亡途径失活来发挥其神经保护作用。
GPS通过抑制小胶质细胞介导的神经炎症和细胞焦亡在PD中表现出神经保护作用，表明其作为PD治疗的有利治疗剂的潜力。
