The protective effect of Cordycepin on diabetic nephropathy through autophagy induction in vivo and in vitro

Diabetic nephropathy (DN) is one of the most serious chronic complications of diabetes mellitus (DM). Autophagy is an important physiological function for podocytes to maintain stability of intracellular environment. In this study, we planned to clarify the effect of Cordycepin, a traditional Chinese medicine, on DN and the related mechanisms. All rats were randomly divided into normal control group, diabetic controls, low-dose group (10 mg/kg), medium-dose group (100 mg/kg), and high-dose group (500 mg/kg). The level of cholesterol, blood sugar, triglyceride, creatinine, and urine protein was examined through an automatic biochemistry analyser. Enzyme-linked immunosorbent assay (Elisa) was used to detect the level of IL-1β, IL-6, and IL-18. HE staining was used to examine histopathologic changes. TUNEL staining was used to detected cell apoptosis. The expression of fibrosis markers α-SMA, t-TG, and TIMP-1, apoptosis-related proteins cleaved-caspase3, Bax and Bcl-2, autophagy markers Beclin1, light chain 3 (LC3)I/II, and p62 were evaluated by western blot. The level of cholesterol, blood sugar, triglyceride, creatinine, and urine protein in the diabetic controls was much higher than that in the normal control group. Obvious histopathology injuries were also found in DN model group. After Cordycepin treatment, all the above indexes were improved compared with the DN group and tissue damages were also alleviated. Further studies showed that Cordycepin suppressed cell apoptosis and renal fibrosis and rescued cell autophagy in DN rat model. Moreover, the results of our in vitro experiments showed that the addition of 3-methyladenine (3-MA, specific autophagy inhibitor) successfully abolished the protective effect of Cordycepin on renal fibrosis through inducing apoptosis and renal fibrosis. The above protective effects of Cordycepin were exhibited in a dose-dependent manner. Cordycepin participated in the modulation of cell apoptosis, fibrosis, and autophagy induction in DN. Our study for the first time revealed that Cordycepin had a certain therapeutic effect on DN in rats through autophagy induction.