Objective:To evaluate the antidiabetic effects of manool in streptozotocin-induced diabetic rats and HepG2 cells.Methods:Diabetes was induced in Wistar rats using streptozotocin and nicotinamide,and animals were treat...Objective:To evaluate the antidiabetic effects of manool in streptozotocin-induced diabetic rats and HepG2 cells.Methods:Diabetes was induced in Wistar rats using streptozotocin and nicotinamide,and animals were treated with two doses of manool(1 and 2 mg/kg).Biochemical,oxidative stress,apoptotic,and inflammatory parameters were assessed,followed by histopathology of the pancreas.Expression of key marker genes in the liver and pancreas was analyzed via qRT-PCR.Catalase and superoxide dismutase activities,malondialdehyde level,and glucose consumption were examined in vitro.Results:Manool significantly reduced fasting glucose level,improved insulin levels,and restored glucokinase and Ki67 expression in rats with diabetes.It also enhanced antioxidant defense,upregulated insulin signaling,activated the mTOR pathway,and promoted β-cell regeneration via increased expression of Pdx1,MAFA,Ngn3,and Ins1 in a dose-dependent manner.However,manool suppressed JAK/STAT pathway only at a higher dose of 2 mg/kg.Histopathological study showed near-normal islet architecture in manool-treated diabetic rats.Conclusions:Manool exerts antidiabetic effects by modulating oxidative stress,inflammation,β-cell regeneration,and insulin sensitivity in diabetic rats.However,further pharmacological and clinical investigations are required before confirming its therapeutic applicability.展开更多
文摘Objective:To evaluate the antidiabetic effects of manool in streptozotocin-induced diabetic rats and HepG2 cells.Methods:Diabetes was induced in Wistar rats using streptozotocin and nicotinamide,and animals were treated with two doses of manool(1 and 2 mg/kg).Biochemical,oxidative stress,apoptotic,and inflammatory parameters were assessed,followed by histopathology of the pancreas.Expression of key marker genes in the liver and pancreas was analyzed via qRT-PCR.Catalase and superoxide dismutase activities,malondialdehyde level,and glucose consumption were examined in vitro.Results:Manool significantly reduced fasting glucose level,improved insulin levels,and restored glucokinase and Ki67 expression in rats with diabetes.It also enhanced antioxidant defense,upregulated insulin signaling,activated the mTOR pathway,and promoted β-cell regeneration via increased expression of Pdx1,MAFA,Ngn3,and Ins1 in a dose-dependent manner.However,manool suppressed JAK/STAT pathway only at a higher dose of 2 mg/kg.Histopathological study showed near-normal islet architecture in manool-treated diabetic rats.Conclusions:Manool exerts antidiabetic effects by modulating oxidative stress,inflammation,β-cell regeneration,and insulin sensitivity in diabetic rats.However,further pharmacological and clinical investigations are required before confirming its therapeutic applicability.