川陈皮素干预阿尔茨海默病作用机制研究进展

Advances in the mechanism of action of nobiletin in Alzheimer’s disease

川陈皮素来源于中药陈皮的多甲氧基黄酮(polymethoxyflavonoids,PMFs)成分,具有抗肿瘤、抗氧化、抗炎、抗肥胖和抗动脉粥样硬化等功效,现代研究发现其在治疗阿尔茨海默病方面具有良好的潜力。阿尔茨海默病(Alzheimer’s disease,AD)是一种神经系统退行性疾病,是严重的健康和社会问题,药物治疗为最常用的治疗手段。川陈皮素通过抑制淀粉蛋白β-分解酶1的活性,增加中性内肽酶的活性,调控cAMP/PKA/ERK,减轻淀粉样蛋白神经毒性;提高乙酰胆碱转移酶的活性、降低乙酰胆碱酯酶活性,增强谷氨酸受体-1的磷酸化水平,提高神经元突触可塑性;调节活性氧、超氧化酶歧化物、丙二醛水平及细胞凋亡相关基因,减轻神经细胞氧化损伤;调节PI2K/AKT和NF-κB信号通路、调控炎症因子水平,减轻神经炎症损伤;逆转Tau蛋白的过度磷酸化,改善微管细胞骨架紊乱;调节胰岛素信号传导和线粒体功能,改善昼夜节律、睡眠周期失调。表明川陈皮素通过多种机制发挥防治AD的作用,但目前关于川陈皮素治疗AD的临床研究尚少,应进一步加强相关研究,以期为AD治疗新药的研发提供前期基础。

Nobiletin is derived from the polymethoxyflavonoids(PMFs)component of the traditional Chinese medicine Chen Pi,which has anti-tumour,antioxidant,anti-inflammatory,anti-obesity and anti-atherosclerotic properties,and modern research has shown it has good potential in the treatment of Alzheimer’s disease(AD).AD is a neurodegenerative disease that is a serious health and social problem and is most commonly treated with drugs.It has been shown that Nobiletin exerts its effects in preventing and treating AD through various mechanisms,by inhibiting the activity of BACE1,increasing the activity of NEP,regulating cAMP/PKA/ERK and reducing Aβneurotoxicity;increasing the activity of CHAT,reducing the activity of ACHE,increasing the phosphorylation level of GLUR1 and improving the synaptic plasticity of neurons;regulating the levels of ROS,SOD,MDA and apoptosis-related genes and reducing oxidative damage to neuronal cells;regulating the PI2K/AKT and NF-κB signaling pathways,modulating levels of inflammatory factors and reducing neuroinflammatory damage;reversing Tau hyperphosphorylation and improving microtubule cytoskeleton disorders;regulating insulin signaling and mitochondrial function and improves circadian rhythm and sleep cycle dysregulation.But there are still few clinical trials of Nobiletin for the treatment of AD,and relevant studies still need to be further strengthened to provide a preliminary basis for the development of new drugs for the treatment of AD.