Ex Vivo Study of the Vasorelaxant Activity Induced by Phenanthrene Derivatives Isolated from Maxillaria densa Priscila Rendó n-Vallejo, † Oswaldo Herna ́ ndez-Abreu, † Jorge Vergara-Galicia, † Ce ́ sar Milla ́ n-Pacheco, ‡ Armando Mejía, ‡ Maximiliano Ibarra-Barajas, § and Samuel Estrada-Soto* ,† † Facultad de Farmacia, Universidad Autó noma del Estado de Morelos, Avenida Universidad 1001, Colonia Chamilpa, 62209. Cuernavaca, Morelos, Me ́ xico ‡ Departamento de Biotecnología, Divisió n de Ciencias Bioló gicas y de la Salud, Universidad Autó noma Metropolitana, Iztapalapa, AP 55-535, Mé xico 09340, D. F. Me ́ xico § Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autó noma de Me ́ xico, Tlalnepantla, Me ́ xico 54090, Me ́ xico * S Supporting Information ABSTRACT: The phenanthrenes gymnopusin (1), fimbriol A (2), and erianthridin (3) from Maxillaria densa were found to induce significant relaxant effects in a concentration-dependent and endothelium-independent manner on aortic rings precontracted with norepinephrine (NE, 0.1 μM) and KCl (80 mM). Compound 1 was the most active and also inhibited the cumulative concentration-response contraction of NE or CaCl 2 . Contractions induced by FPL 64176, an agonist of L- type voltage-dependent calcium channels, were blocked by 1. The potassium channel blockers glibenclamide and TEA (tetraethylammonium) reduced the relaxations induced by 1. Nevertheless, the effect of 1 was not modified by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a specific soluble guanylate cyclase inhibitor. The functional results obtained suggest that 1 induces relaxation through an endothelium-independent pathway by the control of cationic channels (calcium channel blockade and potassium channel opening) in the myogenic response of rat aortic rings. H ypertension, defined as an elevation of systolic and/or diastolic blood pressure to above 140/90 mmHg, is the most common cardiovascular disease. Hypertension is a major risk factor for endothelial dysfunction, metabolic syndrome, renal dysfunction, congestive heart failure, coronary artery disease, and stroke. 1 Antihypertensive drugs influence arterial blood pressure at the sites of four effectors, namely, the resistance vessels, the capacitance vessels, the heart, and the kidney. Accordingly, new antihypertensive agents with new or known therapeutic targets are needed to control hypertension more effectively, with less adverse effects and having a neutral impact on known cardiovascular risk factors. 2 There are many preparations using orchids that are used currently in traditional Chinese medicine for the treatment of several diseases, including hypertension. 3 Phenanthrene de- rivatives are an uncommon class of aromatic metabolites, which presumably are formed by oxidative coupling of the aromatic rings of stilbene precursors. They have been isolated from higher plants as the family Orchidaceae, inclusive of the Bletilla, Bulbophyllum, Coelogyna, Cymbidium, Dendrobium, Ephemer- antha, Epidendrum, Eria, and Maxillaria species. In addition, a large number of phenanthrenes have been reported to possess various biological activities such as antiallergic, anti-inflamma- tory, antimicrobial, antiplatelet aggregations, cytotoxicity, spasmolytic, vasorelaxant effects, and others. 4-6 Thus, in an attempt to find novel antihypertensive compounds with vasorelaxant activity, our group is studying medicinal plants that are used as smooth muscle relaxant agents against diverse ailments. 7,8 In Mexico, Maxillaria densa Lindl. (Orchidaceae) is an indigenous medicinal plant used for the treatment of gastrointestinal diseases. Previously, a dichloro- methane-methanol (50:50) extract from M. densa and the isolated compounds gymnopusin (1), fimbriol A (2), erianthridin (3), 2,5-dihydroxy-3,4-dimethoxyphenanthrene, and nudol showed concentration-dependent inhibition of the spontaneous contractions of rat ileum strips with potencies comparable to that of papaverine. Their spasmolytic effects did not involve a direct nitrergic or antihistaminergic mode of action or interference with calcium influx into the smooth muscle cells. 9 Also, in a previous investigation it was demonstrated that methanolic extracts of the orchids Laelia autumnalis and Laelia anceps showed a significant vasorelaxant activity on contractions induced by norepinephrine (NE) on isolated rat aorta rings, in an endothelium-independent and a concentration-dependent manner. 10-12 Received: August 14, 2012 Published: December 12, 2012 Note pubs.acs.org/jnp © 2012 American Chemical Society and American Society of Pharmacognosy 2241 dx.doi.org/10.1021/np300508v | J. Nat. Prod. 2012, 75, 2241-2245