Fredi Cifuentes1, Javier Palacios2, Jovan Kuzmicic1, Lorena Carvajal1, Fernanda Muñoz1, Cristina Quispe3, Chukwuemeka R Nwokocha4, Glauco Morales5, Ignacio Norambuena-Soto6, Mario Chiong6, Adrián Paredes5. 1. Laboratorio de Fisiología Experimental (EPhyL), Instituto Antofagasta (IA), Universidad de Antofagasta, Antofagasta, Chile. 2. Laboratorio de Bioquímica Aplicada, Instituto de EtnoFarmacologia (IDE), Facultad de Ciencias de la Salud, Universidad Arturo Prat, Av. Arturo Prat Chacón, 2120, Iquique 1110939, Chile. Electronic address: clpalaci@unap.cl. 3. Laboratorio de Bioquímica Aplicada, Instituto de EtnoFarmacologia (IDE), Facultad de Ciencias de la Salud, Universidad Arturo Prat, Av. Arturo Prat Chacón, 2120, Iquique 1110939, Chile. 4. Department of Basic Medical Sciences Physiology Section, Faculty of Medical Sciences, The University of the West Indies, Mona, Kingston 7, Jamaica. 5. Laboratorio de Química Biológica, Instituto Antofagasta (IA), Universidad de Antofagasta, Antofagasta, Chile. 6. Advanced Center for Chronic Diseases, CEMC, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Chile.
Abstract
BACKGROUND: Xenophyllum poposum is an endemic species of the Andes Cordillera, popularly known as Popusa. Popusa is widely used by mountain communities as a folk medicine to treat altitude sickness and hypertension. PURPOSE: The aim of this study is to evaluate the hypotensive effects and vascular reactivity of Popusa extracts and its pure isolated compounds. METHODS: Hydroalcoholic extract of Xenophyllum poposum (HAE X. poposum; 40 mg/kg dose) were administered to rats by gavage and mean arterial pressures were recorded. Organ bath studies were conducted in endothelium-intact and denuded rings, and the vascular reactivity of the HAE X. poposum extract and its isolated compounds were compared and analysed. Cytosolic Ca2+ was measured in vascular smooth muscle cell line A7r5 using Fura2-AM. RESULTS: HAE X. poposum significantly reduced the mean arterial blood pressure and heart rate in normotensive rats chronically treated with the extract, as well as mice acutely treated with the extract. A negative chronotropic effect was observed in the isolated rat heart. HAE X. poposum induced endothelial vasodilation mediated by nitric oxide (NO), reduced the contractile response to PE, and decreased PE-induced intracellular Ca2+ influx in vascular smooth muscle cells. Pure compounds isolated from HAE X. poposum such as 4‑hydroxy‑3-(3-methyl-2-butenyl) acetophenone, 5-acetyl-6‑hydroxy‑2-isopropenyl-2, and 3-dihydrobenzofurane (dihydroeuparin) also triggered endothelium-dependent vasodilation. CONCLUSION: HAE X. poposum decreases blood pressure, heart rate and vascular response. The vasodilation properties of HAE X. poposum extract and its isolated compounds may act through the endothelial nitric oxide synthase, as well as calcium channel blocker mechanisms. The results of the present study provide the first qualitative analysis that supports the use of X. poposum in traditional folk medicine for the treatment of altitude sickness and hypertension.
BACKGROUND:Xenophyllum poposum is an endemic species of the Andes Cordillera, popularly known as Popusa. Popusa is widely used by mountain communities as a folk medicine to treat altitude sickness and hypertension. PURPOSE: The aim of this study is to evaluate the hypotensive effects and vascular reactivity of Popusa extracts and its pure isolated compounds. METHODS: Hydroalcoholic extract of Xenophyllum poposum (HAE X. poposum; 40 mg/kg dose) were administered to rats by gavage and mean arterial pressures were recorded. Organ bath studies were conducted in endothelium-intact and denuded rings, and the vascular reactivity of the HAE X. poposum extract and its isolated compounds were compared and analysed. Cytosolic Ca2+ was measured in vascular smooth muscle cell line A7r5 using Fura2-AM. RESULTS: HAE X. poposum significantly reduced the mean arterial blood pressure and heart rate in normotensive rats chronically treated with the extract, as well as mice acutely treated with the extract. A negative chronotropic effect was observed in the isolated rat heart. HAE X. poposum induced endothelial vasodilation mediated by nitric oxide (NO), reduced the contractile response to PE, and decreased PE-induced intracellular Ca2+ influx in vascular smooth muscle cells. Pure compounds isolated from HAE X. poposum such as 4‑hydroxy‑3-(3-methyl-2-butenyl) acetophenone, 5-acetyl-6‑hydroxy‑2-isopropenyl-2, and 3-dihydrobenzofurane (dihydroeuparin) also triggered endothelium-dependent vasodilation. CONCLUSION: HAE X. poposum decreases blood pressure, heart rate and vascular response. The vasodilation properties of HAE X. poposum extract and its isolated compounds may act through the endothelial nitric oxide synthase, as well as calcium channel blocker mechanisms. The results of the present study provide the first qualitative analysis that supports the use of X. poposum in traditional folk medicine for the treatment of altitude sickness and hypertension.