Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study  

作　　者：Lan-Gen Zhuang Rong Zhang Guo-Xi Jin Xiao-Yan Pei Qiong Wang Xiao-Xu Ge 

机构地区：[1]Department of Endocrinology,The First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,Anhui Province,China [2]Department of Nephrology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China [3]Department of Endocrinology,Tongren Hospital Affiliated to Shanghai Jiao Tong University,Shanghai 200336,China

出　　处：《World Journal of Diabetes》2024年第10期2111-2122,共12页世界糖尿病杂志（英文）

基　　金：Supported by the General Project of Anhui Provincial Health and Construction Commission,No.AHWJ2022b056.

摘　　要：BACKGROUND Diabetic nephropathy(DN)is a severe microvascular complication of diabetes characterized by inflammation,oxidative stress,and renal fibrosis.Asiaticoside(AC)exhibits anti-inflammatory,antioxidant,and anti-fibrotic properties,suggesting potential therapeutic benefits for DN.This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2(NRF2)/heme oxygenase-1(HO-1)antioxidant pathway.METHODS The effects of AC on high glucose(HG)-induced proliferation,inflammation,oxidative stress,and fibrosis were evaluated in rat glomerular mesangial cells(HBZY-1)in vitro.A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury,inflammation,oxidative stress,and fibrosis.The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model.RESULTS AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats,including reduced body weight,and elevated blood glucose,serum creatinine,blood urea nitrogen,and 24-h urine protein.Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin(IL)-6,IL-8,tumor necrosis factor-alpha,reactive oxygen species,and malondialdehyde levels while increasing superoxide dismutase activity.Additionally,AC suppressed the expression of fibrogenic markers such as collagen I,collagen IV,and fibronectin.AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase(Quinone)1 protein expression in renal tissues and HG-induced HBZY-1 cells.CONCLUSION AC improves DN by reducing inflammation,oxidative stress,and fibrosis through the activation of the NRF2/HO-1 signaling pathway.These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic k

关 键 词：ASIATICOSIDE Diabetic nephropathy INFLAMMATION Renal fibrosis Reactive oxygen species 

分 类 号：R587.1[医药卫生—内分泌]