Vasodilator and hypotensive effects of pure compounds and hydroalcoholic extract of Xenophyllum poposum (Phil) V.A Funk (Compositae) on rats

Fredi Cifuentes; Javier Palacios; Jovan Kuzmicic; Lorena Carvajal; Fernanda Muñoz; Cristina Quispe; Chukwuemeka R. Nwokocha; Glauco Morales; Ignacio Norambuena-Soto; Mario Chiong; Adrián Paredes

doi:10.1016/j.phymed.2018.09.226

Vasodilator and hypotensive effects of pure compounds and hydroalcoholic extract of Xenophyllum poposum (Phil) V.A Funk (Compositae) on rats

Fredi Cifuentes, Javier Palacios, Jovan Kuzmicic, Lorena Carvajal, Fernanda Muñoz, Cristina Quispe, Chukwuemeka R. Nwokocha, Glauco Morales, Ignacio Norambuena-Soto, Mario Chiong, Adrián Paredes

Universidad de Chile

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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.

Original language	English
Pages (from-to)	99-108
Number of pages	10
Journal	Phytomedicine
Volume	50
DOIs	https://doi.org/10.1016/j.phymed.2018.09.226
Publication status	Published - Nov 15 2018

Bibliographical note

Publisher Copyright:
© 2018

Funding

Financial support by Network for Extreme Environments Research project (NEXER; Project ANT1756, Universidad de Antofagasta, Chile) and Universidad Arturo Prat (Iquique, Chile; VRIIP0006-17 and VRIIP0209-17 ) are gratefully acknowledged. We are grateful to Mauricio Boric and Alejandra Vielma (Pontificia Universidad Católica de Chile, Facultad de Biología) for assistance with Langendorff isolated heart system. We are grateful to Giovanni Appendino and Federica Pollastro (Dipartimento di Scienze del Farmaco, università degli Studi del Piemonte Orientale A. Avogadro, Novara, Italy) for assistance with Biotage Sp-4 Flash Purification System.

Funders	Funder number
Network for Extreme Environments Research	ANT1756
Universidad Arturo Prat	VRIIP0006-17, VRIIP0209-17
Universidad de Antofagasta

ASJC Scopus Subject Areas

Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine

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10.1016/j.phymed.2018.09.226

Cite this

Cifuentes, F., Palacios, J., Kuzmicic, J., Carvajal, L., Muñoz, F., Quispe, C., Nwokocha, C. R., Morales, G., Norambuena-Soto, I., Chiong, M., & Paredes, A. (2018). Vasodilator and hypotensive effects of pure compounds and hydroalcoholic extract of Xenophyllum poposum (Phil) V.A Funk (Compositae) on rats. Phytomedicine, 50, 99-108. https://doi.org/10.1016/j.phymed.2018.09.226

Cifuentes, F, Palacios, J, Kuzmicic, J, Carvajal, L, Muñoz, F, Quispe, C, Nwokocha, CR, Morales, G, Norambuena-Soto, I, Chiong, M & Paredes, A 2018, 'Vasodilator and hypotensive effects of pure compounds and hydroalcoholic extract of Xenophyllum poposum (Phil) V.A Funk (Compositae) on rats', Phytomedicine, vol. 50, pp. 99-108. https://doi.org/10.1016/j.phymed.2018.09.226

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title = "Vasodilator and hypotensive effects of pure compounds and hydroalcoholic extract of Xenophyllum poposum (Phil) V.A Funk (Compositae) on rats",

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.",

author = "Fredi Cifuentes and Javier Palacios and Jovan Kuzmicic and Lorena Carvajal and Fernanda Mu{\~n}oz and Cristina Quispe and Nwokocha, {Chukwuemeka R.} and Glauco Morales and Ignacio Norambuena-Soto and Mario Chiong and Adri{\'a}n Paredes",

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doi = "10.1016/j.phymed.2018.09.226",

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AU - Cifuentes, Fredi

AU - Palacios, Javier

AU - Kuzmicic, Jovan

AU - Carvajal, Lorena

AU - Muñoz, Fernanda

AU - Quispe, Cristina

AU - Nwokocha, Chukwuemeka R.

AU - Morales, Glauco

AU - Norambuena-Soto, Ignacio

AU - Chiong, Mario

AU - Paredes, Adrián

PY - 2018/11/15

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N2 - 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.

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Vasodilator and hypotensive effects of pure compounds and hydroalcoholic extract of Xenophyllum poposum (Phil) V.A Funk (Compositae) on rats

Abstract

Bibliographical note

Funding

ASJC Scopus Subject Areas

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