Affinin (Spilanthol), Isolated from Heliopsis Longipes, Induces Vasodilation Via Activation of Gasotransmitters and Prostacyclin Signaling Pathways

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Jan 25

PMID 28117739

Citations 6

Authors

Jesus Eduardo Castro-Ruiz

Alejandra Rojas-Molina

Francisco J Luna-Vazquez

Fausto Rivero-Cruz

Teresa Garcia-Gasca

Cesar Ibarra-Alvarado

Affiliations

Soon will be listed here.

Abstract

roots have been widely used in Mexican traditional medicine to relieve pain, mainly, toothaches. Previous studies have shown that affinin, the major alkamide of these roots, induces potent antinociceptive and anti-inflammatory activities. However, the effect of root extracts and affinin on the cardiovascular system have not been investigated so far. In the present study, we demonstrated that the dichloromethane and ethanolic extracts of roots, and affinin, isolated from these roots, produce a concentration-dependent vasodilation of rat aorta. Affinin-induced vasorelaxation was partly dependent on the presence of endothelium and was significantly blocked in the presence of inhibitors of NO, H₂S, and CO synthesis (N-nitro-l-arginine methyl ester (l-NAME), dl-propargylglycine (PAG), and chromium mesoporphyrin (CrMP), respectively); K⁺ channel blockers (glibenclamide (Gli) and tetraethyl ammonium (TEA)), and guanylate cyclase and cyclooxygenase inhibitors (1-[1,2,4]oxadiazolo[4,3-]quinoxalin-1-one (ODQ) and indomethacin (INDO), respectively). Our results demonstrate, for the first time, that affinin induces vasodilation by mechanisms that involve gasotransmitters, and prostacyclin signaling pathways. These findings indicate that this natural alkamide has therapeutic potential in the treatment of cardiovascular diseases.

Citing Articles

Proangiogenic Effect of Affinin and an Ethanolic Extract from Roots: Ex Vivo and In Vivo Evidence.

Garcia-Badillo P, Avalos-Soriano A, Lopez-Martinez J, Garcia-Gasca T, Castro-Ruiz J Molecules. 2021; 26(24).

PMID: 34946751 PMC: 8706137. DOI: 10.3390/molecules26247670.

Development of a quantified herbal extract of hawthorn leaves with vasodilator effect.

Ornelas-Lim C, Luna-Vazquez F, Rojas-Molina A, Ibarra-Alvarado C Saudi Pharm J. 2021; 29(11):1258-1266.

PMID: 34819787 PMC: 8596289. DOI: 10.1016/j.jsps.2021.10.002.

Seedlings. Metabolic Responses Induced by the Alkamide Affinin.

Campos-Garcia T, Molina-Torres J Metabolites. 2021; 11(3).

PMID: 33673570 PMC: 7997251. DOI: 10.3390/metabo11030143.

A Review of Endothelium-Dependent and -Independent Vasodilation Induced by Phytochemicals in Isolated Rat Aorta.

Knox M, Vinet R, Fuentes L, Morales B, Martinez J Animals (Basel). 2019; 9(9).

PMID: 31470540 PMC: 6769919. DOI: 10.3390/ani9090623.

Ethyl Acetate Fraction of Engl. and K. Krause (Anacardiaceae) Trunk Barks Corrects Angiotensin II-Induced Hypertension and Endothelial Dysfunction in Mice.

Nitiema M, Soleti R, Koffi C, Belemnaba L, Mallegol P, Ouedraogo N Oxid Med Cell Longev. 2019; 2019:9464608.

PMID: 31183001 PMC: 6512010. DOI: 10.1155/2019/9464608.

References

Mustafa A, Gadalla M, Snyder S . Signaling by gasotransmitters. Sci Signal. 2009; 2(68):re2. PMC: 2744355. DOI: 10.1126/scisignal.268re2. View

White R, Kryman J, El-Mowafy A, Han G, Carrier G . cAMP-dependent vasodilators cross-activate the cGMP-dependent protein kinase to stimulate BK(Ca) channel activity in coronary artery smooth muscle cells. Circ Res. 2000; 86(8):897-905. DOI: 10.1161/01.res.86.8.897. View

Beltowski J, Jamroz-Wisniewska A . Hydrogen sulfide and endothelium-dependent vasorelaxation. Molecules. 2014; 19(12):21183-99. PMC: 6271169. DOI: 10.3390/molecules191221183. View

Wongsawatkul O, Prachayasittikul S, Isarankura-Na-Ayudhya C, Satayavivad J, Ruchirawat S, Prachayasittikul V . Vasorelaxant and antioxidant activities of Spilanthes acmella Murr. Int J Mol Sci. 2009; 9(12):2724-2744. PMC: 2635640. DOI: 10.3390/ijms9122724. View

Majed B, Khalil R . Molecular mechanisms regulating the vascular prostacyclin pathways and their adaptation during pregnancy and in the newborn. Pharmacol Rev. 2012; 64(3):540-82. PMC: 3400831. DOI: 10.1124/pr.111.004770. View

Decaluwe K, Pauwels B, Verpoest S, Van de Voorde J . Divergent mechanisms involved in CO and CORM-2 induced vasorelaxation. Eur J Pharmacol. 2011; 674(2-3):370-7. DOI: 10.1016/j.ejphar.2011.11.004. View

Derbyshire E, Marletta M . Structure and regulation of soluble guanylate cyclase. Annu Rev Biochem. 2012; 81:533-59. DOI: 10.1146/annurev-biochem-050410-100030. View

Zhao Y, Vanhoutte P, Leung S . Vascular nitric oxide: Beyond eNOS. J Pharmacol Sci. 2015; 129(2):83-94. DOI: 10.1016/j.jphs.2015.09.002. View

Boonen J, Bronselaer A, Nielandt J, Veryser L, De Tre G, De Spiegeleer B . Alkamid database: Chemistry, occurrence and functionality of plant N-alkylamides. J Ethnopharmacol. 2012; 142(3):563-90. DOI: 10.1016/j.jep.2012.05.038. View

10.

Zhang Z, Huang H, Liu P, Tang C, Wang J . Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP channels. Can J Physiol Pharmacol. 2007; 85(12):1248-53. DOI: 10.1139/Y07-120. View

11.

Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Modis K, Panopoulos P . Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci U S A. 2012; 109(23):9161-6. PMC: 3384190. DOI: 10.1073/pnas.1202916109. View

12.

Molina-Torres J, Salazar-Cabrera C, Armenta-Salinas C, Ramirez-Chavez E . Fungistatic and bacteriostatic activities of alkamides from Heliopsis longipes roots: affinin and reduced amides. J Agric Food Chem. 2004; 52(15):4700-4. DOI: 10.1021/jf034374y. View

13.

OSullivan S, Kendall D, Randall M . Vascular effects of delta 9-tetrahydrocannabinol (THC), anandamide and N-arachidonoyldopamine (NADA) in the rat isolated aorta. Eur J Pharmacol. 2005; 507(1-3):211-21. DOI: 10.1016/j.ejphar.2004.11.056. View

14.

Molina-Torres J, Ramirez-Chavez E . Antimicrobial properties of alkamides present in flavouring plants traditionally used in Mesoamerica: affinin and capsaicin. J Ethnopharmacol. 1999; 64(3):241-8. DOI: 10.1016/s0378-8741(98)00134-2. View

15.

Zygmunt P, Petersson J, Andersson D, Chuang H, Sorgard M, Di Marzo V . Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature. 1999; 400(6743):452-7. DOI: 10.1038/22761. View

16.

Yetik-Anacak G, Sorrentino R, Linder A, Murat N . Gas what: NO is not the only answer to sexual function. Br J Pharmacol. 2014; 172(6):1434-54. PMC: 4369255. DOI: 10.1111/bph.12700. View

17.

Carino-Cortes R, Gayosso-De-Lucio J, Ortiz M, Sanchez-Gutierrez M, Garcia-Reyna P, Cilia-Lopez V . Antinociceptive, genotoxic and histopathological study of Heliopsis longipes S.F. Blake in mice. J Ethnopharmacol. 2010; 130(2):216-21. DOI: 10.1016/j.jep.2010.04.037. View

18.

Wu L, Fan N, Lin M, Chu I, Huang S, Hu C . Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine macrophage by down-regulating LPS-induced inflammatory mediators. J Agric Food Chem. 2008; 56(7):2341-9. DOI: 10.1021/jf073057e. View

19.

Acosta-Madrid I, Castaneda-Hernandez G, Cilia-Lopez V, Carino-Cortes R, Perez-Hernandez N, Fernandez-Martinez E . Interaction between Heliopsis longipes extract and diclofenac on the thermal hyperalgesia test. Phytomedicine. 2009; 16(4):336-41. DOI: 10.1016/j.phymed.2008.12.014. View

20.

Nangle M, Cotter M, Cameron N . An in vitro study of corpus cavernosum and aorta from mice lacking the inducible nitric oxide synthase gene. Nitric Oxide. 2004; 9(4):194-200. DOI: 10.1016/j.niox.2004.01.006. View