栀子及其活性成分治疗神经退行性疾病药理作用的研究进展

Research progress of pharmacologic effects of gardenia and its active ingredients on neurodegenerative diseases

神经退行性疾病是种大脑和脊髓的细胞神经元逐渐退化所直接导致的疾病,可造成认知和功能障碍,严重影响患者的生活质量。栀子活性成分可抑制晚期糖基化终产物(the receptor of advanced glycation endproducts, RAGE)信号通路,抑制雷帕霉素靶蛋白(mammalian target of rapamycin, mTOR)信号通路,增强瘦素信号通路,改善胰岛素的信号传递,激活磷脂酰肌醇三激酶(phosphoinositide 3-kinase, PI3K)/蛋白激酶B(protein kinase B,Akt)/生长关联蛋白43(growth associated protein 43,GAP43)信号通路,上调羟甲基戊二酰辅酶A还原酶降解泛素连接酶复合物(hydroxymethyl glutaryl CoA reductase degrades protein 1,HRD1)的表达,以抑制β-淀粉样蛋白(amyloid-β,Aβ)沉积。栀子活性成分可抑制抑制Toll样受体4(Toll like receptor 4,TLR4)/核转录因子κB(nuclear factorκB,NF-κB)信号通路激活,下调TLR2/TLR4/髓样分化因子88(myeloid differentiation primary response 88,MyD88)通路,抑制环氧合酶-2(cyclooxygenase-2,COX-2)的表达,以降低神经炎性损伤;可增强细胞自噬,促进神经功能恢复。栀子活性成分可降低氧化应激反应,减轻神经组织损伤;通过改善线粒体功能,维持突触正常功能;可下调mTOR信号通路,激活细胞外调节蛋白激酶(extracellular regulatory protein kinase, ERK)1/2-氧化还原调节核因子E_(2)相关因子2(nuclear factor erythroid-2 related factor 2,Nrf2)信号通路,降低神经细胞凋亡;可阻止Tau蛋白过度磷酸化,减轻神经组织损伤。栀子活性成分可改善胆碱能传递,保护多巴胺能神经元,以调节神经递质的表达。

The active ingredients of Gardenia jasminoides can inhibit the the receptor of advanced glycation endproducts(RAGE)signaling pathway,inhibit the mammalian target of rapamycin(mTOR)signaling pathway,enhance the leptin signaling pathway,improve insulin signaling,activate the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/growth associated protein 43(GAP43)signaling pathway,up-regulate the expression of hydroxymethylglutaryl CoA reductase to degrade hydroxymethyl glutaryl CoA reductase degrades protein 1(HRD1),and inhibit amyloid-β(Aβ)deposition.The active ingredients of Gardenia jasminoides can inhibit the activation of Toll like receptor 4(TLR4)/nuclear factorκB(NF-κB)signaling pathway,down-regulate the TLR2/TLR4/myeloid differentiation primary response 88(MyD88)pathway,inhibit the expression of cyclooxygenase-2(COX-2),and improve neuroinflammatory damage.The active ingredients of Gardenia jasminoides can enhance cellular autophagy and promote the recovery of neurological function.The active ingredients of gardenia can reduce oxidative stress response and alleviate nerve tissue damage.The active ingredients of Gardenia jasminoides can improve mitochondrial function and maintain normal synaptic function.The active ingredients of Gardenia jasminoides can down-regulate the mTOR signaling pathway,activate the extracellular regulatory protein kinase(ERK1/2)/nuclear factor erythroid-2 related factor 2(Nrf2)signaling pathway,and reduce neuronal apoptosis.The active ingredients of Gardenia jasminoides can prevent excessive phosphorylation of Tau protein and alleviate nerve tissue damage.The active ingredients of Gardenia jasminoides can improve cholinergic transmission,protect dopaminergic neurons,and regulate the expression of neurotransmitters.