Hepatic gluconeogenesis inhibition by four traditional used, hypoglycemic plants

Type 2 diabetes (T2D) is characterized by insulin resistance combined with a relative deficiency in insulin secretion [1]. In T2D the liver plays a key role in maintaining blood glucose levels during fasting by synthesizing glucose, mainly from pyruvate and amino acids (gluconeogenesis) [2]. In T2D with overt fasting hyperglycemia (> 140 mg/dl,), an excessive rate of hepatic glucose output is the major abnormality responsible for the elevated fasting plasma glucose. In Mexico, besides the prescribed drugs for the treatment of Type 2 diabetes, people use medicinal plants attempting to control their hyperglycaemic state. Generally, they prepare infusions that are drunk during the day, between meals. We documented in our field work at different communities of Mexico, four medicinal plants used by the people to treat T2D; Ageratina petiolaris (AP), Bromelia karatas (BK), Rhizophora mangle (RM) and Smilax moranensis (SM). We previously proved that they exert a chronic and acute hypoglycemic effect in diabetic rats. We hypothesize that one possible mechanism of action for these plants is through inhibition of hepatic gluconeogenesis. We tested the effect of extracts from these plants on gluconeogenesis by performing pyruvate tolerance tests in fasted Wistar rats and analyzing their effect on the in vitro activity of glucose -6-phosphatase from hepatic rat microsomes.

The in vivo results showed that AP, RM and SM reduce the hyperglycemic peak at 30 min after the administration of pyruvate, with only AP and RM sustaining the effect up to 120 min, in vitro AP, RM and SM inhibited the activity of the enzyme (table 1). We conclude that the extracts of AP, RM and SM can inhibit gluconeogenesis both in vivo and in vitro.

[1] ADA AD. Classification and Diagnosis of Diabetes. Diabetes Care 2015; 38: S8-S16.

[2] Guyton AC, Hall JE. Textbook of Medical Physiology. 11th ed. Philadelphia, Pennsylvania: Elsevier, 2006