Evaluation of Vascular Activity of the Neolignan Conocarpan and Its Mechanism of Action

Purpose: Conocarpan (CNP) is a neolignane being in some plants used in folk medicine, whose functions are little known. Identifying its biological potential is an important tool in the search for alternative therapies for the treatment of diseases with high rates of morbidity and mortality, such as cardiovascular diseases. Methods: Male Wistar rats (200–250 g) were used to obtain the mesenteric arterial bed for perfusion experiments. The aortic, pulmonary artery, and second branch of the mesenteric artery rings were used in vascular reactivity. The interaction of conocarpan with the receptor of interest was evaluated using molecular docking. Results: In perfusion of the mesenteric arterial bed, increasing concentrations of conocarpan almost completely reduced the vascular resistance generated by phenylephrine. In vascular reactivity from rings of the aorta and pulmonary artery, relaxation promoted by conocarpan was of little significance; in second branch of mesenteric artery rings with endothelium, there was total relaxation, while in rings without endothelium, this effect was drastically reduced. Regarding the mechanisms of action, among all tested antagonists (atropine, glibenclamide, 4-aminopyridine, iberiotoxin, indomethacin, loratadine and ODQ) on relaxation induced by conocarpan in second branch of mesenteric artery isolated, in the presence of loratadine (H1 receptor antagonist), conocarpan showed a significant reversal of contractile capacity in tested concentrations. Molecular docking showed an affinity for the receptor, reinforcing it as a possible target. Conclusion: Conocarpan has a vasodilating action, especially on resistance vessels. Likewise, its mechanism of action seems to act in an endothelium-dependent pathway, probably by H1 histaminergic receptors.