Arjunolic acid from Cyclocarya paliurus ameliorates diabetic retinopathy through AMPK/mTOR/HO-1 regulated autophagy pathway

Cyclocarya paliurus (CP) is a traditional Chinese herb and possesses a variety of biological activities including anti-hyperglycemia, anti-hyperlipidemia, antioxidant and anti-inflammation. Arjunolic acid (AA) is an abundant and bioactive ingredient in CP that shows significant protection against many metabolic diseases such as diabetic complication. Diabetic retinopathy (DR) is a serious complication of diabetes and may lead to vision loss. However, the protective effects and underlying mechanisms of AA against DR is not still understood.We aimed to investigate whether AA activates AMPK/mTOR/HO-1 regulated autophagy pathway to alleviate DR.In the study, the STZ-induced diabetic model of rats was established, and AA with 10 and 30 mg/kg dosages was given orally for ten weeks to investigate their effect on retinal injury of DR. H2O2-induced ARPE-19 cells were applied to evaluate anti-apoptosis and anti-oxidant effect of AA.The results revealed that AA could prevent STZ-induced weight loss and increase the retinal thickness and nuclei counts. The level of HO-1 protein was upregulated both in vivo and in vitro. In addition, AA prevented retinal damage and cell apoptosis through the AMPK-mTOR-regulated autophagy pathway. Furthermore, anti-apoptosis capacity, as well as the expression of HO-1 and LC3 protein, were effectively locked by AMPK inhibitor dorsomorphin dihydrochloride (compound C).This finding implies that AA may be a promising candidate drug by protecting retinal cells from STZ-induced oxidative stress and inflammation through the AMPK/mTOR/HO-1 regulated autophagy pathway.