Berberine elevates mitochondrial membrane potential and decreases reactive oxygen species by inhibiting the Rho/ROCK pathway in rats with diabetic encephalopathy

Abstract

Objectives Diabetic encephalopathy (DE) is a serious complication of diabetes mainly occurring in the elderly patients. Berberine (BBR) is an isoquinoline alkaloids extracted from Coptis chinensis that is applied in the treatment of diabetes clinically. This study explored the possible mechanism of BBR in relieving DE. Methods Wistar rats were injected with streptozotocin and fed a high fat diet to establish the model of DE. The model rats were treated with BBR. The body weight, blood glucose and insulin of rats were measured, and Morris water maze test was conducted to evaluate the learning and memory abilities. The pathological conditions of cortical tissues were detected. The cortical mitochondria membrane potential (MMP) and reactive oxygen species (ROS) were monitored. The expressions of Rho/ROCK pathway-related genes of rat cortex were detected. The changes of MMP and ROS were detected after the treatment of Rho/ROCK pathway activator. Results The body weight of model rats changed little, and levels of blood glucose and insulin were increased. The spatial learning and memory abilities were impaired, with disordered cortical neurons, and obvious neurons apoptosis and glia proliferation. BBR alleviated cognitive dysfunction and pathological damage in rats with DE. BBR enhanced cortical MMP and suppressed ROS. BBR treatment inhibited the Rho/ROCK pathway. Activation of the Rho/ROCK pathway reversed the effects of BBR on MMP and ROS. Conclusion BBR elevated MMP and reduced ROS in rats with DE by inhibiting the Rho/ROCK pathway. This study may offer novel insights for the management of DE.