Combination of Astragaloside II and Notoginsenoside Fc Ameliorated Apoptosis and Mitochondrial Oxidative Stress in Diabetes with Acute Kidney Injury via activating PDGFB and inhibiting SHP-1/VEGFA pathway

Abstract

Abstract Acute kidney injury (AKI) is a disease with high morbidity and mortality and ischemia-reperfusion (IR) injury is the main cause of AKI. It has been reported that hyperglycemia was a crucial risk factor for renal IRI in diabetes patients with renal IR-induced AKI. Whereas there is no effective treatment. Here, we explored the nephroprotective effects of combination of Astragaloside II and Notoginsenoside Fc on diabetes with IR-induced AKI and its potential mechanisms. We established hyperglycemia with renal hypoxia reoxygenation (H/R) injury model in vivo and in vitro. We first found that combination of Astragaloside II and Notoginsenoside Fc could improve biochemical indexes and renal histologic injury in model mice. We provided relevant evidence that combination of Astragaloside II and Notoginsenoside Fc significantly reduced apoptosis level. In addition, our data suggested that combination of Astragaloside II and Notoginsenoside Fc could have inhibited effects on oxidative stress and NLRP3 activation, further suppressing inflammatory cell aggregation and inflammatory factor secretion. Further studies found that the combination of Astragaloside II and Notoginsenoside Fc could prevent SHP-1-induced VEGF inhibition and activate PDGFB to ameliorate renal tubular epithelial cells (TECs) function. In conclusion, our study indicated that combined treatment of Astragaloside II and Notoginsenoside Fc exerted beneficial protective effects on renal tubular injury and mitochondrial oxidative stress in diabetes with ischemia-reperfusion induced AKI via activating PDGFB and inhibiting SHP-1/VEGFA signaling pathway. Therefore, combination of Astragaloside II and Notoginsenoside Fc may be a potential therapeutic strategy to treat diabetes with IR-induced AKI.