| Objective: Diabetic nephropathy(DN)is a progressive kidney disease as a result of long-term hyperglycemia in diabetic patients,that underlying mechanism is complex and lack of effective treatments.Various active ingredients in Chinese herbs have been showed the ability to alleviate renal injury and improve DN in recent years.Phillyrin,a natural medicinal active compound extracted from the Oleaceae family,has been demonstrated to possess various pharmacological effects including anti-oxidative,anti-apoptosis and anti-obesity.However,the role of Phillyrin and its underlying mechanism in DN has not yet been explored.Methods: To investigate the effects of Phillyrin on DN and its potential mechanisms of action,we performed experiments using the STZ-induced DN mice as models.The levels of FBG and HBALC,BUN,Scr and β2-Mg in serum were detected.The pathological injury and the levels of SOD and MDA in kidney were evaluated by HE staining.The effects of Phillyrin on Akt、p-Akt、GSK-3β、p-GSK-3β、M-Cyto C、C-Cyto C、Bcl-2、Bax、caspase-3、cleaved caspase-3 expression in kidney in DN mice were detected by western blot.Result: Phillyrin could significantly reduce the levels of fasting blood glucose and Hb Alc,downregulated the levels of serum BUN,Scr and β2-MG,and improved the pathological changes of the kidney in DN mice model.Phillyrin also increased the level of antioxidant and attenuated oxidative damage in DN model mice.In addition,Phillyrin inhibited GSK-3β activity by activating the PI3K/Akt signaling pathway,and then increased the Bcl-2/Bax ratio,reduced the release of cytochrome c from the mitochondria to the cytoplasm,subsequently inhibited the activation of caspase-3,and ultimately suppressed renal cell apoptosis.Discussion: These finding suggested that Phillyrin could be a new promising therapeutic strategies for DN,and this protective effect might be related to suppressing oxidative stress and apoptosis via the PI3K/Akt/GSK-3β pathway. |
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