Yu Nu compound regulates autophagy and apoptosis through mTOR in vivo and vitro
Background: Yu Nu compound (YNJ) is a traditional Chinese medicine widely utilized to treat type 2 diebetes, which has been reported to regulate autophagy. Abnormal podocyte autophagy and apoptosis could result in podocyte loss in diabetics nephropathy (DN). The mechanism of Yu Nu compound in DN is still unclear. Therefore, the study aims to investigate how Yu Nu compound exerts effects on DN rats.Methods: GK rats were administered using YNJ with different dose once a day by gavage for 4 weeks.
... gavage for 4 weeks. The renal cortex injury was observed by HE and electron microscope. Cell apoptosis of renal cortex was analyzed by tunnel staining. The mTOR, autophagy-related proteins and apoptosis-related proteins were detected by Western blot or Real-time PCR in vivo and vitro. MPC5 cells were exposed to high glucose (HG, 30mM) for 12h for simulating podocytes injury in DN. MPC5 cells were treated by serum containing YNJ with different dosage. Cell activities and apoptosis were respectively detected through CCK8 assay and Flow cytometry.Results: The results showed that the medium dose of YNJ has better effects on decreasing blood glucose and improving renal injury in GK rats, followed by decreasing mTOR levels. The autophagy levels were enhanced, accompanied with the increase of cell apoptosis in vivo and vitro. The decreasing endogenous mTOR could reverse the effects of YNJ on cell apoptosis and autophagy.Conclusion : the study suggested that YNJ reduced the excessive autophagy and suppressed apoptosis through regulating mTOR. The maintenance of normal basal autophagic activity possibly based on the effect of YNJ on multiple target was essential for maintaining podocytes function.