Senna alata leaf extract restores insulin sensitivity in high-fat diet-induced obese mice

Background: Senna alata (S. alata) has numerous pharmacological activities including anti-lipogenic effect in highfat diet (HFD)-induced obese mice. The present study investigated the effect of Senna alata (S. alata) leaf extracts on the regulation of abnormal glucose metabolism in HFD-induced obese mice. Methods: Male ICR mice were induced to become obese by being fed a HFD (45 kcal% lard fat) for 12 weeks. During the last 6 weeks of diet feeding, the obese mice were treated with the water extract of S. alata leaf at 250 and 500 mg/kg/day. After 6 weeks of treatment, blood was collected for measuring biochemical parameters. The liver, epididymal fat and skeletal muscle tissues were excised and kept for determining histology and western blot analysis. Results: Treatment with S. alata (250 and 500 mg/kg) significantly reduced hyperglycemia, hyperinsulinemia, and hyperleptinemia. The glucose intolerance was improved by S. alata. The elevated monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) levels in obese mice were reduced in S. alata treatment. The level of serum adiponectin was increased in obese mice treated with S. alata (250 and 500 mg/kg). The epididymal fat weight was reduced in S. alata treatment. The enlarged adipocyte size was smaller in obese mice treated with S. alata. In comparison with the obese control mice, the mice treated with S. alata showed a significant reduction of liver glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) proteins. Moreover, S. alata up-regulated the liver and muscle adenosine monophosphate-activated protein kinase phosphorylation (pAMPK) and muscle glucose transporter 4 (GLUT4). Conclusions: The results indicate that the restoration of impaired glucose metabolism of S. alata may be associated with reduced hepatic gluconeogenesis and increased glucose uptake via AMPK activation.