Hypoglycemic effects of esculeoside A are mediated via activation of AMPK and upregulation of IRS-1

BACKGROUND: Tomato fruit (Lycopersicon esculentum Mill.) has been suggested to be useful for the prevention of diabetes. Esculeoside A is the main saponin compounds in tomatoes. This study investigated the hypoglycemic effects and the underlying mechanism of esculeoside A in C57BLKS/Leprdb (db/db) mice. METHODS: Wild-type C57BLKS (db/dm) mice were used in the db/dm mouse group and db/db mice were randomly divided into 2 groups: untreated and treated db/db mouse groups. Esculeoside A (100 mg/kg) was administered by gavage for 56 days to the treated db/db mouse group. Distilled water was administered to the db/dm mouse group and the untreated db/db mouse group. The blood and liver biochemical parameters and the expression of liver insulin signaling-related proteins were examined. RESULTS: The results showed that esculeoside A reduced the fasting blood glucose (FBG) levels and improved the glucose tolerance. Further investigation revealed that hepatic protein expressions of total AMP-activated protein kinase (T-AMPK), phosphorylated AMP-activated protein kinase (p-AMPK), insulin receptor substrate-1 (IRS-1), and glucokinase (GCK) were significantly upregulated after esculeoside A treatment. In contrast, the hepatic protein expression of phosphoenolpyruvate carboxykinase (PEPCK) was significantly downregulated by esculeoside A treatment. CONCLUSION: These findings suggested that esculeoside A has a potential of alleviating the metabolic abnormalities in db/db mice via regulation of AMPK/IRS-1 pathway. Our findings supported a possible application of esculeoside A as a functional supplement for diabetes treatment.