ABSTRACT
In West Indian folklore, a variety of plants are used for medicinal purposes. One such plant, Bixa orellana (annatto), is commonly used in the treatment of diabetes mellitus. Preliminary studies have shown that a crude annatto seed extract exhibited either glucose lowering or hyperglycaemia-inducing activity depending on how it was further manipulated. This present investigation sought to determine the effects of the glucose-lowering extract on C-peptide and streptozotocin-induced diabetic dogs. This annatto extract was found to decrease blood glucose levels in fasting normoglycaemic and streptozotocin-induced diabetic dogs. In addition, in normal dogs, it suppressed the postprandial rise in blood glucose after an oral glucose load. Interestingly, the extract also caused an increase in insulin-to-glucose ratio in normal dogs. Increased insulin levels were not due to increased insulin synthesis as after 1-h residence time and half-hour postprandial, decreased C-peptide levels was observed. It was concluded that Bixa orellana (annatto) lowered blood glucose by stimulating peripheral utilization of glucose, and it is possible that this glucose-lowering extract might be of pharmacological importance.
Subject(s)
Bixaceae/chemistry , Carotenoids/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Plant Extracts/pharmacology , Animals , Blood Glucose/drug effects , C-Peptide/drug effects , C-Peptide/metabolism , Carotenoids/isolation & purification , Dogs , Female , Hypoglycemic Agents/isolation & purification , Insulin/blood , Male , Medicine, Traditional , Plant Extracts/isolation & purification , Postprandial Period , Streptozocin , Time Factors , West IndiesABSTRACT
Various plants are used in Caribbean folklore for the treatment of a variety of illnesses including diabetes mellitus. Preliminary investigations of several crude plant extracts have indicated that the annatto (Bixa orellana), among others, does in fact exhibit hypoglycaemic properties. This present investigation sought to isolate the hypoglycaemic principle(s) from the crude extract and to determine the mechanism of action. Purification experiments employing thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) resulted in an oil-soluble, partially purified annatto extract. The latter caused a decrease in blood glucose level of 5.62+/-0.13 (n=34) mmol/dL versus 6.31+/-0.12 (n=34) for the control (p<0.01) 1 h after administration. This hypoglycaemia persisted for an additional hour when the oral glucose tolerance test (OGTT) was performed on dogs treated with annatto and compared with the control. Plasma insulin levels measured at 1.0 h showed that there was an increase in plasma insulin levels of 59.57+/-8.3 microIU/mL for the annatto treated dogs versus 40.95+/-5.46 microIU/mL for the control (p<0.05), this elevation persisted throughout the duration of the OGTT which followed. Insulin receptor studies, using a modification of the method of Gambhir et al. done on mononuclear leucocytes and erythrocytes obtained from blood taken 1 h after administration showed that there was an increase in the percentage receptor binding when compared with the control. Insulin affinity results showed that there was an increase of 1.8+/-0.2x10(8) m-1 (n=12) in mononuclear leucocytes for the annatto treated dogs versus 1.2+/-0.2x10(8) m-1 for the control (p<0.05). In the enythrocytes, there was also an increase in affinity from 1.2+/-0.2x10(8) m-1 to 2.3+/-0.2x10(8) m-1 for the control and treated animals, respectively. In conclusion, it can be stated that annatto is responsible for the hypoglycaemic episodes seen in the dogs which was mediated by an increase in plasma insulin concentration as well as an increase in insulin binding on the insulin receptor due to elevated affinity of the ligand for the receptor.
