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-f...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.展开更多
Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and...Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were examined.Results:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities.Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity.Furthermore,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal.Conclusions:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.展开更多
基金Supported by the General Project of Anhui Provincial Health and Construction Commission,No.AHWJ2022b056.
文摘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.
文摘Objective:To evaluate the effect of asiaticoside on streptozotocin(STZ)and nicotinamide(NAD)-induced carbohydrate metabolism abnormalities and deregulated insulin signaling pathways in rats.Methods:Asiaticoside(50 and 100 mg/kg body weight)was administered to STZ-NAD-induced diabetic rats for 45 days,and its effects on hyperglycaemic,carbohydrate metabolic,and insulin signaling pathway markers were examined.Results:Asiaticoside increased insulin production,lowered blood glucose levels,and enhanced glycolysis by improving hexokinase activity and suppressing glucose-6-phosphatase and fructose-1,6-bisphosphatase activities.Abnormalities in glycogen metabolism were mitigated by increasing glycogen synthase activity and gluconeogenesis was decreased by decreasing glycogen phosphorylase activity.Furthermore,asiaticoside upregulated the mRNA expressions of IRS-1,IRS-2,and GLUT4 in STZ-NAD-induced diabetic rats and restored the beta cell morphology to normal.Conclusions:Asiaticoside has the potential to ameliorate type 2 diabetes by improving glycolysis,gluconeogenesis,and insulin signaling pathways.
