Aralia taibaiensi,widely distributed in western China,particularly in the Qinba Mountains,has been utilized as a folk medicine for treating diabetes,gastropathy,rheumatism,and cardiovascular diseases.Saponins from A.t...Aralia taibaiensi,widely distributed in western China,particularly in the Qinba Mountains,has been utilized as a folk medicine for treating diabetes,gastropathy,rheumatism,and cardiovascular diseases.Saponins from A.taibaiensis(sAT)have demonstrated protective effects against oxidative stress and mitochondrial dysfunction induced by ischemia/reperfusion(I/R).However,the underlying mechanisms remain unclear.In vivo,middle cerebral artery occlusion/reperfusion(MCAO/R)induced inflammatory infiltration,neuronal injury,cell apoptosis,mitochondrial dysfunction,and oxidative stress in the ischaemic penumbra,which were effectively mitigated by sAT.sAT increased the mRNA and protein expression levels of apelin and its receptor apelin/apelin receptors(ARs)both in vivo and in vitro.(Ala13)-Apelin-13(F13A)and small interfering RNA(siRNA)abolished the regulatory effects of sAT on neuroprotection mediated by adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/protein kinase B(Akt).Furthermore,sAT induced apelin/AR expression by simultaneously inhibiting P38 mitogen-activated protein kinase(P38 MAPK)/activating transcription factor 4(ATF4)and upregulating hypoxia-inducible factor-1α(HIF-1α).Our findings indicate that sAT regulates apelin/AR/AMPK by inhibiting P38 MAPK/ATF4 and upregulating HIF-1a,thereby suppressing oxidative stress and mitochondrial dysfunction.展开更多
基金supported by the National Science Foundation of China(No.81903832),the Key Research and Development Plan of Shaanxi Province(No.2022SF-182),the Fundamental Research Funds for the Central Universities(No.D5000210799)Shaanxi Provincial Traditional Chinese Medicine Administration"Double Chain Integration"Middle Youth Research and Innovation Team Project(No.2022-SLRH-LJ-007)Shanghai Science and Technology Innovation Action Plan(No.22S21902600).
文摘Aralia taibaiensi,widely distributed in western China,particularly in the Qinba Mountains,has been utilized as a folk medicine for treating diabetes,gastropathy,rheumatism,and cardiovascular diseases.Saponins from A.taibaiensis(sAT)have demonstrated protective effects against oxidative stress and mitochondrial dysfunction induced by ischemia/reperfusion(I/R).However,the underlying mechanisms remain unclear.In vivo,middle cerebral artery occlusion/reperfusion(MCAO/R)induced inflammatory infiltration,neuronal injury,cell apoptosis,mitochondrial dysfunction,and oxidative stress in the ischaemic penumbra,which were effectively mitigated by sAT.sAT increased the mRNA and protein expression levels of apelin and its receptor apelin/apelin receptors(ARs)both in vivo and in vitro.(Ala13)-Apelin-13(F13A)and small interfering RNA(siRNA)abolished the regulatory effects of sAT on neuroprotection mediated by adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/protein kinase B(Akt).Furthermore,sAT induced apelin/AR expression by simultaneously inhibiting P38 mitogen-activated protein kinase(P38 MAPK)/activating transcription factor 4(ATF4)and upregulating hypoxia-inducible factor-1α(HIF-1α).Our findings indicate that sAT regulates apelin/AR/AMPK by inhibiting P38 MAPK/ATF4 and upregulating HIF-1a,thereby suppressing oxidative stress and mitochondrial dysfunction.
