Diabetic nephropathy(DN)is one of the most common complications of diabetes mellitus,which is characterized in renal tubulointerstitial fibrosis(TIF).The current study was designed to investigate the protective effect of Jujuboside A(Ju A)on TIF in type 2 diabetes(T2DM)mice,and explore its underlying anti-fibrosis mechanism.A mouse T2DM model was established using high fat diet(HFD)feeding combined with intraperitoneal injection of streptozotocin(STZ).Then,diabetic mice were treated with Ju A(10,20 and 40 mg·kg-1·d-1,i.g.)for 12 weeks.Results showed that administration of Ju A not only down-regulated fasting blood glucose(FBG)levels,but also improved hyperlipidemia and renal function in diabetic mice.Moreover,the reduced ECM accumula-tion was observed in the renal cortex of Ju A treated diabetic mice,while the TIF progression was also attenuated by Ju A through blocking the epithelial-to-mesenchymal transition(EMT)of renal tubular epithelial cells(RTECs).Further mechanism studies showed that Ju A treatment effectively down-regulated the protein expression and subsequent nuclear translocation of Yin Yang 1(YY1)in the renal cortex of diabetic mice,and reduced the levels of transforming growth factor-β1(TGF-β1)in the serum and renal cortex of Ju A treated mice.According to in vitro studies,the up-regulated YY1/TGF-β1 signaling pathway was restored by Ju A in high glucose(HG)cultured HK-2 cells.Taken together,these findings demonstrated that Ju A can ameliorate the TIF of DN through down-regulat-ing the YY1/TGF-β1 signaling pathway.

LIU Yang-Yang;LI Lin;JI Bei;HAO Shi-Long;KUANG Xiao-Feng;CAO Xin-Yun;YUAN Jia-Yu;JIANG Zhen-Zhou;QIAN Si-Tong;WEI Chu-Jing;XU Jing;YIN Xiao-Xing;LU Qian;YANG Ting-Ting

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy,Xuzhou Medical University,Xuzhou 221004,China;New Drug Screening Center,Jiangsu Center for Pharmacodynamics Research and Evaluation,China Pharmaceutical Uni-versity,Nanjing 210009,China

中国天然药物

[1]LIU Yang-Yang;LI Lin;JI Bei;HAO Shi-Long;KUANG Xiao-Feng;CAO Xin-Yun;YUAN Jia-Yu;JIANG Zhen-Zhou;QIAN Si-Tong;WEI Chu-Jing;XU Jing;YIN Xiao-Xing;LU Qian;YANG Ting-Ting-.Jujuboside A ameliorates tubulointerstitial fibrosis in diabetic mice through down-regulating the YY1/TGF-β1 signaling pathway)[J].中国天然药物,2022(09):656-668

Jujuboside

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