Vasodilatory study of Mitragyna speciosa (Korth.) Havil methanolic extract using rats aortic ring assay

Mitragyna speciosa, also known as ketum, has been traditionally used in Southeast Asia for managing fatigue, pain, and hypertension. In Malaysia, the leaf decoction is consumed to alleviate symptoms associated with elevated blood pressure. However, the potential vasodilatory activity of M. speciosa and its possible mechanisms of action remain poorly understood.

This study was designed as an initial ex vivo investigation of the vasodilatory activity of the methanolic leaf extract of M. speciosa (KME) and to elucidate the underlying mechanisms of vascular relaxation.

The ex vivo vasodilatory effects of KME were evaluated using isolated rat thoracic aortic rings. Endothelium-dependent pathways, such as the nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway and muscarinic receptors, were studied using pharmacological inhibitors. The roles of ion channels, including potassium (K⁺) and calcium (Ca²⁺) channels, were also assessed. The alkaloid profile of KME was determined using a well-established UPLC-MS/MS method.

KME produced concentration-dependent relaxation in precontracted aortic rings under ex vivo conditions. Mitragynine exhibited a similar relaxation profile and could be a significant contributor to the vasorelaxant activity of KME. Endothelial denudation and inhibition of NO/sGC/cGMP signalling pathway significantly reduced the KME-induced relaxation, indicating an endothelium-dependent mechanism in this model. Muscarinic receptor blockade also reduced the relaxation response. Potassium and calcium-channel-related mechanisms contributed partially to the response. UPLC-MS analysis revealed that mitragynine is the major indole alkaloid in KME, along with speciociliatine, speciogynine, corynantheidine, paynantheine, and mitraciliatine.

KME demonstrated concentration-dependent ex vivo vasorelaxant activity in isolated rat aortic rings, primarily though endothelium-dependent NO/sGC/cGMP and partial contributions from muscarinic receptors and ion channels. These findings provide preliminary mechanistic support for the traditional use of M. speciosa in blood pressure-related conditions; however, they do not establish in vivo antihypertensive efficacy. Further in vivo, molecular, pharmacokinetic, and safety studies are required to clarify its pharmacological profile and therapeutic relevance.