熊胆粉活性成分熊去氧胆酸(ursodesxycholic acid,UDCA)、牛磺熊去氧胆酸(taurour-sodeoxycholic acid,TUDCA)在不同的神经系统疾病动物模型中具有神经保护作用.其中UDCA、TUDCA可通过抑制丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路中细胞外调节蛋白激酶(extracellular regulated protein kinase,ERK)、c-Jun 氨基末端激酶(c-Jun N-terminal kinasa,JNK)、p38 MAPK的磷酸化发挥抗神经炎症的作用;UDCA通过激活单磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)/雷帕霉素靶蛋白(mechanistic target of rapamycin,mTOR)和抑癌基因诱导的假定激酶蛋白1(PTEN induced putative kinase 1,PINK1)/RBR E3泛素蛋白连接酶(RBR E3 ubiquitin-protein ligase,Parkin)信号通路,抑制小鼠帕金森病(parkinson's disease,PD)中神经细胞凋亡,增加线粒体自噬起到改善线粒体功能障碍和神经保护的作用.熊胆粉、TUDCA通过上调 G 蛋白偶联受体(G protein-coupled bile acid receptor 5,TGR5)的表达抑制蛋白激酶 B(protein kinase B,Akt)/核因子-κB(nuclear factor-KB,NF-κB)信号通路的激活及调控巨噬细胞的分化,减轻神经炎症反应,保护神经细胞;TUDCA下调蛋白激酶R样内质网激酶(protrin kinase R-like ER kinase,PERK)/PERK-真核细胞起始因子 2α(eukaryotic initiation factor 2α,eIF2α)/转录激活因子 4(activating transcription factor 4,ATF4)/C/EBP 同源蛋白(C/EBP-homologous protein,CHOP)信号通路的表达,上调CIBZ基因的表达,激活核因子E2相关因子2(nuclear factor-erythroid 2 related factor 2,Nrf2)/NADPH 醌氧化还原酶 1(NADPH quinone oxidoreductase 1,NQO1)、TGR5/去乙酰化酶 3(recombinant sirtuin 3)等信号通路,抑制内质网应激、氧化应激所引起的神经细胞调亡,TUDCA通过调节细胞自噬和能量代谢抑制细胞凋亡发挥神经保护作用.现将近年来对熊胆粉、UDCA、TUDCA治疗神经系统病作用机制进行综述,为熊胆粉及其活性成分的临床运用提供参考.
Research progress on the mechanism of bear bile powder and its active ingredients in the treatment of nervous system diseases
Ursodesxycholic acid(UDCA)and tauroursodeoxycholic acid(TUDCA),the active components of bear bile powder,have neuroprotective effects in different animal models of nervous system diseases.Among them,UDCA and TUDCA can play anti-neuroinflammatory role by inhibiting the phospho-rylation of extracellular regulated protein kinase(ERK),c-Jun N-terminal kinasa(JNK)and p38 MAPK in mitogen-activated protein kinase(MAPK)signaling pathway.By activating AMP-activated protein kinase(AMPK)/mechanistic target of rapamycin(mTOR)and PINK1/Parkin signaling pathways,UDCA inhibits neuronal apoptosis in Parkinson's disease(PD)model mice and increases mitophagy to play a improve mitochondrial dysfunction and neuroprotective role.By up-regulating the expression of G protein-coupled bile acid receptor 5(TGR5),bear bile powder and TUDCA inhibit the activation of serine threonine kinase(Akt)/nuclear factor-KB(NF-κB)signaling pathway and regulate the differentiation of macrophages,reduce neuroinflammation and protect nerve cells.TUDCA down-regulated the expression of protein kinase R-like ER kinase(PERK)/PERK-eukaryotic initiation factor 2α(eIF2α)/activating tran-scription factor 4(ATF4)/C/EBP-homologous protein(CHOP)signaling pathway.Up-regulation of CIBZ gene expression,activation of nuclear factor-erythroid 2 related factor 2(Nrf2)/NADPH quinone oxidoreductase 1(NQO1),TGR5/recombinant sirtuin 3 and other signaling pathways,inhibit neuronal apoptosis caused by endoplasmic reticulum stress and oxidative stress.TUDCA inhibits apoptosis by regulating autophagy and energy metabolism play a neuroprotective role.This article reviews the mechanism of the active components of bear bile powder in the treatment of nervous system diseases in recent years,and provides a reference for the clinical application of bear bile powder and its active components.
bear bile powderursodesxycholic acidtauroursodeoxycholic acidnervous system diseasesmechanism of action
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