The Lignan (‐)‐Cubebin Inhibits Vascular Contraction and Induces Relaxation Via Nitric Oxide Activation in Isolated Rat Aorta

Abstract

Cubebin, the most abundant lignan in Piper cubeba, has been described as having several effects as trypanocidal, antimycobacterial, antispasmodic, antimicrobial, anti-inflammatory, and analgesic. This study investigated the vasorelaxant effect produced by (-)-cubebin in isolated rat aortic rings pre-contracted with phenylephrine (Phe), and the possible mechanism involved in this event was evaluated. Endothelium-dependent relaxation was evoked by acetylcholine and (-)-cubebin in intact aortic rings, while endothelium-independent vasorelaxation was elicited by sodium nitroprusside and (-)-cubebin in denuded rings. Cumulative concentration-response curves for Phe (10(-10) -10(-5) M) were determined for endothelium-intact and endothelium-denuded aortic rings in either the presence or absence of (-)-cubebin. Dose-response curves were also constructed for pre-incubation of vascular rings with Nω-nitro-L-arginine methyl ester (L-NAME) (a non-specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) (a guanylyl cyclase inhibitor). (-)-Cubebin was found to exert a vasorelaxant effect irrespective of the presence of endothelium, which was abolished by pretreatment with L-NAME and ODQ, but not with indomethacin. In addition, (-)-cubebin was able to reduce Phe contraction in the case of intact rings. These results suggest that (-)-cubebin promotes vasorelaxation via NO/cGMP pathway in rat aorta, without prostacyclin involvement.

Antiparasitic Activity and Characterization of Lignans from the Ethanolic Extract of Zanthoxylum monogynum A. St-Hil. Leaves

“…13 Its leishmanicidal, antimicrobial, antioxidant, vasodilator action, sexual stimulant, antimutagenic, and analgesic properties have also been reported. 23,[26][27][28][29][30][31] Compounds 3 e 4 were identified in a mixture soluble in chloroform. GC-MS data showed two peaks for this sample.…”

Medicinal Attributes of Lignans Extracted from Piper Cubeba: Current Developments

“…[56] Carvalho et al investigated the effect produced by (À)-cubebin from the dried seeds of P. cubeba on the contractility and relaxation of rat aortic rings with phenylephrine to evaluate the possible mechanism involved.I tw as suggested that (À)-cubebin elicited endothelium-dependenta nd endothelium-independent vascular relaxation in rat aorta mediated by the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway without prostanoid participation. [57]…”

Cubebin: A Small Molecule with Great Potential

“…20,21 Assim, a ocorrência dessa lignana pode estar relacionada com o sistema de defesa da planta em sinergia com outros metabolitos. 22 Entre as muitas atividades biológicas desta lignana que serão discutidas neste artigo algumas delas despertam maior interesse por parte dos pesquisadores, devido à importância da descoberta, bem como os estudos pioneiros sobre a atividade antichagásica da cubebina e seus derivados sintéticos, 6 estimulação na melanogénese, 10 atividade i i itória so re a e zi a redutase 5α-testosterona, 11 atividade anti-androgênica, 25 atividade vasodilatadora 15,26 e citotoxicidade. 27,28 Apesar da cubebina apresentar muitas atividades biológicas in vitro e in vivo, bem como outras lignanas, esta molécula chama a atenção devido à sua ocorrência em várias espécies de plantas, facilidade de obtenção de derivados semisintéticos e ainda atividades biológicas de extrema importância o que torna a cubebina uma molécula de grande interesse químico e farmacológico.…”

“…A disfunção erétil masculina ocorre quando a enzima fosfodiesterase (PDE 5) inibe o GMPc que é responsável pelo relaxamento da musculatura lisa nos corpos cavernosos do pênis aumentando o fluxo de sangue levando à ereção, os medicamentos usados atualmente contra a disfunção erétil como o citrato de sildenafil inibem essa enzima, embora ainda não confirmado este também pode ser o mecanismo de ação da (-)-cubebina. 15 Carvalho et al, 26 também avaliaram o efeito vasodilatador da (-)-cubebina na relaxação da aorta isoladas de ratos utilizando anéis com e sem endotélio, com a intenção de avaliar a influência do mesmo sobre o relaxamento. O grupo com endotélio teve seu relaxamento utilizando acetilcolina e (-)-cubebina, já os anéis sem endotélio foram tratados com nitroprussiato de sódio e (-)-cubebina.…”