Cortex Mori Radicis extract promotes neurite outgrowth in diabetic rats by activating PI3K/AKT signaling and inhibiting Ca(2+) influx associated with the upregulation of transient receptor potential canonical channel 1

Cortex Mori Radicis extract (CMR) has various pharmacological properties, such as anti-inflammatory, anti-allergic and anti-hyperglycemic effects. However, the effects and mechanisms of CMR in the neuroregeneration of diabetic peripheral neuropathy (DPN) are unclear. In the present study, the effects of CMR on neurite outgrowth of dorsal root ganglia (DRG) neurons in diabetic rats were investigated and its underlying mechanisms were explored. SD rats were subjected to a high-fat diet with low-dose streptozotocin to induce a Type II diabetes model with peripheral neuropathy. CMR was then applied for four weeks continuously with or without injection of small interfere (si)RNA targeting the transient receptor potential canonical channel 1 (TRPC1) via the tail vein. Blood glucose levels, the number of Nissl bodies, neurite outgrowth and growth cone turning in DRG neurons were evaluated. The expression of TRPC1 protein, Ca(2+) influx and activation of the PI3K/AKT signaling pathway were also investigated. The results of the present study showed that CMR significantly lowered blood glucose levels, reversed the loss of Nissl bodies, induced neurite outgrowth and restored the response of the growth cone of DRG neurons in diabetic rats. CMR exerted neurite outgrowth-promoting effects by increasing TRPC1 expression, reducing Ca(2+) influx and enhancing AKT phosphorylation. siRNA targeting TRPC1 in the CMR group abrogated its anti-diabetic and neuroregenerative effects, suggesting the involvement of TRPC1 in the biological effects of CMR on DPN.