The Metabolism and Disposition of Koumine, Gelsemine and Humantenmine from Gelsemium

Abstract

Background: Gelsemium is a toxic flowering plant of the Gelsemiaceae family. It is used to treat skin diseases in China, and it is an important medicinal and homeopathic plant in North America. Up to now, more than 200 compounds have been isolated and reported from Gelsemium. More than 120 of these are indole alkaloids, including the main components, koumine, gelsemine and humantenmine which produce the pharmacological and toxicological effects of Gelsemium. However, their clinical application their limited by its narrow therapeutic window. Therefore, it is very important to study the metabolism and disposition of indole alkaloids from Gelsemium before their clinical application. This paper reviews all the reports on the metabolism and disposition of alkaloids isolated from Gelsemium at home and abroad. Methods: The metabolism and disposition of alkaloids from Gelsemium were searched by the Web of Science, NCBI, PubMed and some Chinese literature databases. Results: Only koumine, gelsemine and humantenmine have been reported, and few other alkaloids have been described. These studies indicated that the three indole alkaloids are absorbed rapidly, widely distributed in tissues, extensively metabolized and rapidly eliminated. There are species differences in the metabolism of these alkaloids, which is the reason for the differences in their toxicity in animals and humans. Conclusion: This review not only explains the pharmacokinetics of indole alkaloids from Gelsemium but also facilitates further study on their metabolism and mechanism of toxicity.

Enhanced oral bioavailability of koumine by complexation with hydroxypropyl-β-cyclodextrin: preparation, optimization, ex vivo and in vivo characterization

“…According to the experimental parameters from published reports, it is found that the absolute bioavailability (Fabs) of KME is only 1% (Wang et al. 2019 ). However, the pharmacokinetics of KME in rats and beagle dogs have also been previously investigated in our laboratory.…”

Orally Administered Koumine Persists Longer in the Plasma of Aged Rats Than That of Adult Rats as Assessed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

“…There are several possible explanations for the differences in the pharmacokinetics of KM in aged rats. First, the increased plasma concentrations of KM due to the low CL in the aged rats could be either or partly due to the altered activity of CYP450, resulting in slower formation of metabolites and faster metabolism saturation or binding by plasma proteins (Zhang et al, 2015;Hu et al, 2017;Wang et al, 2019). CYP3A4/3A5 may be the main enzyme responsible for KM metabolism by the liver microsomes; the KM metabolic pathway in liver microsomes involves oxidization, demethylation, and dehydrogenation (Zhang et al, 2013;Hu et al, 2017;Xiao et al, 2017;Zuo et al, 2020).…”

Streptozotocin-Induced Hyperglycemia Affects the Pharmacokinetics of Koumine and its Anti-Allodynic Action in a Rat Model of Diabetic Neuropathic Pain

“…Further, our previous studies have reported that KM elimination occurs majorly through liver microsomes ( Wei et al, 2016 ; Wei et al, 2017 ). The KM metabolic pathway in liver microsomes involves oxidization, demethylation, and dehydrogenation ( Wang et al, 2019 ). Diabetes affects the metabolism of proteins, carbohydrates, and lipids, and may be directly or indirectly involved in drug biotransformation.…”