Studies of the Hypoglycemic Action of Salsolinol in Type 2 Diabetic Mice

[Speaker] Ming-Jai Su:1
[Co-author] Chen-Yen Tsai:1, Chi-Tun Ruan:1, Chi-Huan Yeh:2, Chao-Min Hsu:2, Sheng-Fa Task:3, Shoes-Sheng Lee:3
1:Institute of Pharmacology, College of Medicine, National Taiwan University, Taiwan, 2:ZIH YUAN TANG Biotechnology Co., Ltd, Taipei City, Taiwan, 3:School of Pharmacy, National Taiwan University, Taiwan

Background: Salsolinol is an alkaloid found in herbal plants and animals. It is produced by hypothalamic neurons and was reported to play a physiological function in regulation of pituitary prolactin secretion. Here we aimed to investigate the pharmacological actions of Salsolinol in diet- induced type 2 diabetic mice.
Methods: Diabetes (blood glucose levels >150 mg/dL), was induced in ICR mice after 4 weeks feeding with a fat-rich chow diet and fructose-sweetened water. The mice were then divided into three groups, including control (RO water) group, salsolinol-treated group and glibenclamide-treated groups. Besides, C2C12 skeletal muscle cells were used in this study.
Results: Oral administration of salsolinol at 3 and 10 mg/Kg significantly attenuated fasting glucose and induced insulin secretion in diet-induced diabetic mice. It attenuated the elevation of plasma glucose induced by an OGTT in diabetic mice. The plasma glucose lowering activity of salsolinol (10 mg/Kg) is comparable to that of glibenclamide (10 mg/Kg).Besides, 2-weeks treatment with salsolinol (10 mg/Kg/day) resulted in a significant reduction in plasma cholesterol, plasma triglyceride, adipocyte size and epididymal fat weight/body weight ratio. Moreover, salsolinol significantly increase glycogen content both in liver and skeletal muscles. In comparison with salsolinol, glibenclamide failed toreduce plasma triglyceride level and increase liver glycogen content. In cultured C2C12 cells, salsolinol induced concentration-dependent transient activation of AMPK at 1 to 10 uM.
Conclusion: the mechanisms of salsolinol in the hypoglycemic effect may be related to the stimulation of AMPK and increase of insulin release. Although the clear mechanisms for the antidiabetic effects of salsolinol remains to be determined, our study suggest that salsolinol can be a potent agent for the treatment of diabetes in future.
Keywords: diabetes, salsolinol, glibenclamide, AMPK
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