期刊
JOURNAL OF NUTRITION HEALTH & AGING
卷 22, 期 6, 页码 710-717出版社
SPRINGER FRANCE
DOI: 10.1007/s12603-018-1015-7
关键词
Berberine; aging; cognitive deficits; skeletal muscle; insulin resistance; mitochondrial biogenesis
资金
- Science and Technology Development Projects of Jilin Province [20140203011YY, 20150311013YY, 20170520020JH]
- National Natural Science Foundation of China [81503122]
- Norman Bethune Program of Jilin University [2015224, 2015401]
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. 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-1 alpha in skeletal muscle were examined by Western blot. 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-1 alpha and increased the production of ATP in the skeletal muscle of aging rats (p < 0.01). Berberine markedly ameliorates aging-related reductions in cognitive ability and muscular function, and the activation of the AMPK/SIRT1/PGC-1 alpha pathway in skeletal muscle may be the underlying protective mechanism of berberine on muscular function.
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