Phytochemical characterization of Tabernanthe iboga root bark and its effects on dysfunctional metabolism and cognitive performance in high-fat-fed C57BL/6J mice

Root bark of the African shrub Tabernanthe iboga has been used in traditional medicine for fatigue, ritual neuro-stimulation, and diabetes treatment. Its main alkaloid, ibogaine, is known for reducing opioid craving. Using metabolomics, researchers identified five phenolic compounds and 30 alkaloids in the water extract, seven alkaloids previously unreported from the root bark. In male mice fed a high-fat diet for 10 weeks to induce metabolic syndrome, supplementing the diet with low or high doses of iboga extract did not improve increased body weight, plasma glucose, lipids, insulin, leptin, or most inflammatory markers. Only the low dose reduced the inflammatory mediator MCP-1. The high dose impaired spatial learning and memory in water maze tests, suggesting negative effects on cognition.

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Abstract

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.