Cortex Mori Radicis Attenuates Streptozotocin-induced Diabetic Renal Injury in Mice via Regulation of Transient Receptor Potential Canonical Channel 6

Abstract

Objective: Cortex Mori Radicis (CMR) has been reported to possess antipyretic, anti-convulsant, anti-allergic, anti-inflammatory, and anti-diabetic effects. In this study, we aimed to investigate the effect of CMR on streptozotocin (STZ)-induced diabetic renal injury in mice and explore the underlying mechanism. Methods: Mice were gavaged with different doses of CMR for continuous 7 days. Then, STZ (50 mg/kg) was applied to induce renal injury associated with type 1 diabetes. Firstly, blood glucose levels and metabolic parameters were evaluated, including weight, food intake, and excrement. HE and PAS staining were performed to examine renal histological changes. Renal inflammation, fibro-sis, and oxidative stress were assayed by real-time PCR and ELISA, separately. Additionally, podo-cyte-related markers, such as nephrin and wilms' tumor-1 (WT-1), were detected by immunohisto-chemical staining and Western blot separately. Lastly, expression of transient receptor potential canonical channel 6 (TRPC6) and activation of MAPK signaling pathways were assayed. Results: CMR pretreatment significantly lowered the blood glucose levels, suppressed renal in-flammation, fibrosis, and oxidative stress, and relieved renal pathological injury, accompanying the inhibition of nephrin and WT-1 expression in STZ-induced diabetic mice. Moreover, CMR de-creased the expression of TRPC6 and suppressed the phosphorylation of ERK, but not P38 MAPK and JNK. Notably, the application of hyperforin, a specific activator of TRPC6, significantly abro-gated the hypoglycemic effect of CMR and reversed the suppression of CMR on TRPC6 expression and ERK activation in the diabetic mice. Conclution: Our findings indicated that CMR attenuated early renal injury in STZ-induced diabetic mice by inhibiting ERK signaling via regulation of TRPC6, suggesting that CMR can be considered as a promising candidate for the management of diabetes-related renal complications.