Preparations of the root bark of Tabernanthe iboga have long been used in Central and West African traditional medicine to combat fatigue, as a neuro-stimulant in rituals, and for treatment of diabetes. The principal alkaloid of T. iboga, ibogaine, has attracted attention in many countries around the world for providing relief for opioid craving in drug addicts. Using a plant metabolomics approach, we detected five phenolic compounds, including 3-O-caffeoylquinic acid, and 30 alkaloids, seven of which were previously reported from T. iboga root bark. Following a report that iboga extracts contain insulinotropic agents, we aimed to determine the potential alleviating effects of the water extract of iboga root bark on high-fat diet (HFD)-induced hyperglycemia as well as its effects on cognitive function in male C57BL/6J mice. Feeding a HFD to mice for 10 weeks produced manifestations of metabolic syndrome such as increased body weight and increased plasma levels of glucose, triacylglycerols, total cholesterol, LDL-cholesterol, insulin, leptin, and pro-inflammatory mediators (IL-6, MCP-1, ICAM-1), as compared to mice fed a low-fat diet (LFD). Supplementation of HFD with iboga extract at ibogaine doses of 0.83 (low) and 2.07 (high) mg/kg/day did not improve these HFD-induced metabolic effects except for a reduction of plasma MCP-1 in the low dose group, indicative of an anti-inflammatory effect. When the HFD mice were tested in the water maze, the high-dose iboga extract caused hippocampus-dependent impairments in spatial learning and memory, as compared to mice receiving only a HFD.

Root bark preparations of the Gabonese plant Tabernanthe iboga (T. iboga) has long been used in traditional medicine in Central and West African regions for the management of type 2 diabetes (T2D). This study is the first investigation of in vivo hypoglycaemic activity in healthy rats and anti-hyperglycaemic activity of T. iboga in a 10% fructose-fed (40 mg/kg (i.p.) streptozotocin (STZ) injected type 2 diabetic rat model.T. iboga at 50 to 200 mg/kg induced hypoglycaemia activity over 3 hours fasted glucose tolerance in healthy Wistar rats and anti-hyperglycaemic effects on non-fasted and fasted blood glucose in fructose-fed STZ T2D rats with no toxicity.Fructose-fed STZ T2D rats developed characteristic type 2 diabetic complications over 6 weeks exhibiting significantly elevated fasting and non-fasting blood glucose, polydipsia, reduced body weight gain and glucose and insulin tolerance compared with STZ alone and normal control rats. T. iboga (50 mg/kg and 200 mg/kg bw) administered p.o. once daily for 4 weeks significantly improved diabetic symptoms of polydipsia, reduced body weight, hyperglycaemia, glucose and insulin tolerance (as AUC) compared with fructose-fed STZ T2D rats. T. iboga aqueous extract (50 mg/kg and 200 mg/kg) also significantly reversed altered actions of marker enzymes of liver including alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, HbA1c and elevated triglycerides in fructose-fed STZ type 2 diabetic rats. Our outcomes show that daily oral provision of T. iboga improves type 2 diabetes complications, superior to glibenclamide, in rat fructose-fed STZ model and offers the potential for safe clinical management of T2D in Gabon.

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