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

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 kidney diseases characterized by oxidative stress and inflammation.

血清骨标志物与2型糖尿病患者心血管疾病风险的关系

目的评估2型糖尿病(T2DM)患者中6种骨标志物(骨钙蛋白、骨桥蛋白、骨粘连蛋白、骨保护素、碱性磷酸酶和骨硬化蛋白)水平是否与心血管疾病(CVD)风险相关。方法选取2015年9月-2018年12月蚌埠医学院第一附属医院收治的T2DM患者200例,其中100例在2年的随访过程中出现了CVD。根据随访期间是否发生CVD分为CVD组和无CVD组,每组100例。用多重试剂盒法测量血清中6种骨标志物,使用多因素Logistic回归分析评估骨标志物与CVD风险的关系。结果CVD组年龄、糖尿病病程、骨钙蛋白、骨桥蛋白、骨粘连蛋白、骨保护素、碱性磷酸酶、骨硬化蛋白水平较无CVD组高(P<0.05)。多因素Logistic回归分析结果显示,较高血浆浓度的骨桥蛋白水平[OR^^=5.112(95%CI:1.032,22.423),P=0.000]是T2DM患者发生CVD的危险因素。结论高骨桥蛋白是T2DM患者CVD风险的独立危险因素,而其他5种骨标志物和CVD风险无关。