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- Title
Berberine Improves Cognitive Deficiency and Muscular Dysfunction via Activation of the AMPK/SIRT1/PGC-1a Pathway in Skeletal Muscle from Naturally Aging Rats.
- Authors
Yu, Y.; Zhao, Y.; Teng, F.; Li, J.; Guan, Y.; Xu, J.; Lv, X.; Guan, F.; Zhang, Ming; Chen, L.
- Abstract
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<0.01). Furthermore, berberine treatment helped normalize the disordered alignment and the decreased number of muscle fibers (p<0.01) in the skeletal muscle of 24 mo rats. Berberine decreased the levels of ROS in both the serum and the skeletal muscle of 24 mo rats (p<0.01). Berberine increased the protein expression of p-AMPK, SIRT1 and PGC-1α and increased the production of ATP in the skeletal muscle of aging rats (p<0.01).Conclusions: Berberine markedly ameliorates aging-related reductions in cognitive ability and muscular function, and the activation of the AMPK/SIRT1/PGC-1α pathway in skeletal muscle may be the underlying protective mechanism of berberine on muscular function.
- Subjects
COGNITION disorders; MUSCLE diseases; REACTIVE oxygen species; ADENOSINE triphosphatase; AGING; ALKALOIDS; ANIMAL experimentation; CARRIER proteins; CELLULAR signal transduction; CHOLESTEROL; COGNITION; DIAGNOSTIC reagents &; test kits; GENE expression; GLUCOSE tolerance tests; HYDROLASES; INTRAPERITONEAL injections; INSULIN resistance; MUSCLES; PROTEIN kinases; RATS; STAINS &; staining (Microscopy); TRANSCRIPTION factors; TRIGLYCERIDES; WESTERN immunoblotting; SKELETAL muscle; PREVENTION
- Publication
Journal of Nutrition, Health & Aging, 2018, Vol 22, Issue 6, p710
- ISSN
1279-7707
- Publication type
Article
- DOI
10.1007/s12603-018-1015-7