Lignans derived from Eucommia ulmoides Oliver(Eucommia lignans)inhibit the progression of inflammatory diseases,while their effect on the progression of diabetic nephropathy(DN)remained unclear.This work was designed ...Lignans derived from Eucommia ulmoides Oliver(Eucommia lignans)inhibit the progression of inflammatory diseases,while their effect on the progression of diabetic nephropathy(DN)remained unclear.This work was designed to assess the function of Eucommia lignans in DN.The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS.The binding between Eucommia lignans and aldose reductase(AR)was predicted by molecular docking.Eucommia lignans(200,100,and 50 mg·kg^(-1))were used in model animals to evaluate their renal function changes.Rat glomerular mesangial cells(HBZY-1)were transfected with sh-AR,sh-AMPK,and oe-AR in the presence of high glucose(HG)or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis.Eucommia lignans significantly attenuated the progression of DN in vivo.Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury,while downregulating the levels of Cyto c,caspase 9,AR,and NOX4 in HBZY-1 cells.In contrast,HG-induced downregulation of Nrf2,HO-1 and p-AMPKαlevels were abolished by Eucommia lignans.Meanwhile,knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression,and AR overexpression reversed the effect of Eucommia lignans.Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis.Thus,these findings might provide evidence for the use of Eucommia lignans in treating DN.展开更多
基金supported by the National Development of Key Novel Drugs for Special Projects of China(No.2017ZX09304014)the National Natural Science Foundation of China(No.82003929)+1 种基金Hunan Provincial Natural Science Foundation of China(No.2021JJ40993)Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples(No.2017TP1037).
文摘Lignans derived from Eucommia ulmoides Oliver(Eucommia lignans)inhibit the progression of inflammatory diseases,while their effect on the progression of diabetic nephropathy(DN)remained unclear.This work was designed to assess the function of Eucommia lignans in DN.The major constituents of Eucommia lignans were analyzed by UPLC-Q-TOF-MS/MS.The binding between Eucommia lignans and aldose reductase(AR)was predicted by molecular docking.Eucommia lignans(200,100,and 50 mg·kg^(-1))were used in model animals to evaluate their renal function changes.Rat glomerular mesangial cells(HBZY-1)were transfected with sh-AR,sh-AMPK,and oe-AR in the presence of high glucose(HG)or HG combined with Eucommia lignans to evaluate whether Eucommia lignans affected HG-induced cell injury and mitochondrial dysfunction through the AR/Nrf2/HO-1/AMPK axis.Eucommia lignans significantly attenuated the progression of DN in vivo.Eucommia lignans notably reversed HG-induced upregulation of inflammatory cytokines and mitochondrial injury,while downregulating the levels of Cyto c,caspase 9,AR,and NOX4 in HBZY-1 cells.In contrast,HG-induced downregulation of Nrf2,HO-1 and p-AMPKαlevels were abolished by Eucommia lignans.Meanwhile,knockdown of AR exerted similar therapeutic effect of Eucommia lignans on DN progression,and AR overexpression reversed the effect of Eucommia lignans.Eucommia lignans alleviated renal injury through the AR/Nrf2/HO-1/AMPK axis.Thus,these findings might provide evidence for the use of Eucommia lignans in treating DN.
基金This work was supported by the National Natural Science Foundation of China(81874137)the Outstanding Youth Foundation of Hunan Province(2018JJ1047)+4 种基金the Huxiang Young Talent Project(2016RS3022)the Hunan Province Science and Technology Talent Promotion Project(2019TJ-Q10)the Project of Scientific Research Plan of Health and Family Planning Commission of Hunan Province(c20180476)the Fundamental Research Funds for the Central South University(2018zzts938)the Wisdom Accumulation and Talent Cultivation Project of the Third Xiangya Hosipital of Central South University(ZC060001 and YX202007).
