Berberine Improves Cognitive Deficiency and Muscular Dysfunction via Activation of the AMPK/SIRT1/PGC-1a Pathway in Skeletal Muscle from Naturally Aging Rats

Objective The manifestations of aging include cognitive deficits and muscular dysfunction, which are closely linked to impairment of mitochondrial biogenesis. Berberine, an isoquinoline alkaloid, presents multiple anti-diabetic pharmacological effects. Evidence has indicated that insulin resistance and cognitive impairment share the same pathogenesis, and berberine could reverse glucose metabolism abnormalities and muscle mitochondrial dysfunction induced by a high-fat diet. This study was used to investigate whether berberine could be used as an anti-aging drug to prevent cognitive deficits and muscular dysfunction in natural aging. Methods Biochemical indicators and an intraperitoneal glucose tolerance test were tested in 5-monthold rats (5 mo group), 24-month-old rats (24 mo group) and 24-month-old rats that had undergone 6 months of berberine treatment (BBR group). A Morris water maze test was conducted to assess the cognitive ability of the rats. Insulin resistance in whole-body was evaluated by intraperitoneal glucose tolerance test (IPGTT). The morphology of the skeletal muscle tissue was observed by hematoxylin-eosin (HE) staining. The levels of total cholesterol, triglyceride, ATP and reactive oxygen species (ROS) were assessed with corresponding reagent kits. The protein expressions of GLUT4, AMPK, SIRT1 and PGC-1α in skeletal muscle were examined by Western blot. Results The results showed that administration of berberine for 6 months significantly improved cognitive deficits and insulin resistance in naturally aging rats (p