雷公藤内酯醇及其衍生物的神经保护作用及机制

Neuroprotective effects of triptolide and its derivatives and their mechanisms of action

雷公藤是我国的传统中药,雷公藤内酯醇是雷公藤提取物中具有抗炎和免疫调节活性功能的主要成分。近年来,大量证据表明,雷公藤内酯醇及其衍生物(雷公藤氯内酯醇和5-羟雷公藤内酯醇)对帕金森病、阿尔茨海默病、多发性硬化等神经变性疾病具有明确的神经保护作用。现代药理学研究表明,雷公藤内酯醇及其衍生物的神经保护作用机制与其抑制小胶质细胞活化及炎性反应因子释放、抑制氧化应激、拮抗兴奋性氨基酸毒性、抑制钙超载以及促进神经营养因子的合成有关。进一步的研究表明,雷公藤内酯醇及其衍生物主要通过影响MAPKs和NF-κB信号转导通路发挥神经保护作用。

Tripterygium wilfordii hook.f.is a kind of herb in traditional Chinese medicine（TCM）.Triptolide（T10） is the major active component of tripterygium extracts which possesses potent anti-inflammatory and immunosuppressive properties.Recently,more and more evidences have indicated that T10 and its analogues（tripchlorolide and 5-hydroxytriptolide） had neuroprotective effects on various neurodegenerative diseases,such as Parkinson＇s disease（PD）,Alzheimer＇s disease（AD） and multiple sclerosis（MS）.Their neuroprotective mechanisms were involved in the inhibiting of microglial activation and release of pro-inflammatory cytokines,attenuating oxidative stress,suppression of excitotoxicity and Ca2＋ overloading,and increasing the production of neurotrophic factors.The underlying molecular mechanisms were found to be associated with mitogen-activated protein kinases（MAPKs） and NF-κB signal pathways.