Caracterização Farmacológica do efeito vasodilatador do extrato hidroetanólico de folhas frescas da Alpinia zerumbet (ALE)

Abstract

Introdution: The rising use of herbal medications globally emphasizes the importance of understanding their pharmacological mechanisms. Alpinia zerumbet, native to West Asia and widely distributed in Brazil, has been identified for its medicinal properties and is included in the RENISUS list. At the time the leaves of this plant have traditionally been used among the population to treat hypertension, and research on its pharmacological mechanisms is rare. Recent studies from our group have demonstrated that hydroethanolic extract from fresh leaves of Alpinia zerumbet (ALE) exhibits a high content of polyphenols and contains notably vasodilatory effects. Because of the essential role of vasodilatation in the antihypertensive treatment, it is crucial to pharmacologically characterize the extract. Material and Methods: Two hundred and forty male Wistar rats were used, which had free access to food and water and were fed with a standard diet. At three months of age, the rats were euthanized using a CO2 chamber, alongside to isolate the mesenteric arterial bed (LAM). Then, the LAM was transferred to a precision perfusion system, preserved at 37 °C, and arrested with a carbogenic mixture. The vasodilatory mechanism of ALE was evaluated using several blockers and antagonists. Results: The results demonstrated that ALE triggered a vasodilatory effect, induced by endothelium, that was inhibited by deoxycholic acid. Besides, perfusion with L-Name, hemoglobin, and ODQ resulted in a decrease in vasodilatation. When the LAM was incubated with elevated potassium (K +), the vasodilatory effect was diminished which was further noted with the use of charybdotoxin (ChTx) and apamin. Remarkably, when the preparation was incubated with a blend of L-Name and elevated potassium, the inhibition of vasodilatation was almost complete. Additionally, perfusion with PP2 and Wortmanin led to a reduction of vasodilatation mediated by the extract. The vascular endothelium plays a fundamental role in modulating vascular tone through the release of factors such as nitric oxide (NO), which is responsible for initiating GMPc production in smooth muscle cells. NO may activate potassium channels, especially calcium-activated potassium (BKca, IK and SKca) channels, which are crucial for hyperpolarization and following vasodilatation. Despite that, the vasodilatory effect of ALE may also be mediated through calcium-independent pathways that are key to NO production. Conclusion: In sum, this study provides valuable insights into the vasodilatory mechanisms of ALE, emphasizing the importance of endothelium, also, the fundamental role of the combination of NO-GMPc pathway and hyperpolarization on its antihypertensive effect.