Gluconeogenesis inhibition and phytochemical composition of two Cecropia species

Cecropia obtusifolia and Cecropia peltata are plants highly used by the Mexican diabetic population to treat type 2 diabetes. Previous studies have assessed their hypoglycemic effect in animal models and in type 2 diabetic patients. Both plants contain cholorogenic acid, an inhibitor of glucose-6-phosphate translocase. In this work, we found a mechanism by which to understand how these plants could produce the observed hypoglycemic effect according to their traditional use. To test the hypothesis that targeting gluconeogenesis with an inhibitor of Gl-6-P translocase could result in a reduction of hepatic glucose production, we examined the effects of Cecropia obtusifolia and Cecropia peltata on gluconeogenesis (in vivo) and the activity of the enzyme (in vitro).

The extracts of the two plants were analyzed by HPLC to confirm their phytochemical composition. To test the inhibition of gluconeogenesis in vivo, a pyruvate tolerance test (2g/kg) was performed in 18-h fasted n5-STZ rats. The effect of the extracts (Cecropia obtusifolia and Cecropia peltata 150 mg/kg) on glucose-6-phosphatase activity was assayed in vitro with intact rat liver microsomes.

Using HPLC-DAD, we confirmed that the main components of both species are chlorogenic acid and isoorientin. Diabetic rats treated with the extracts showed a lower glucose curve. The tested extracts were able to reduce the increase in the glucose blood level, and they inhibited the glucose-6-P activity with IC(50)s of 224 microg/ml for Cecropia obtusifolia aqueous, 160 microg/ml for Cecropia obtusifolia butanolic, 146 microg/ml for Cecropia peltata aqueous and 150 microg/ml for Cecropia peltata butanolic.

The results of the experiments presented here suggest that the administration of both plants can improve glycemic control by blocking the hepatic glucose output, especially in the fasting state. These data support the traditional use of the plants as "agua de uso", a cold infusion of the plant consumed over the course of a day.