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

Int J Mol Sci. 2017 Jan 22;18(1):218. doi: 10.3390/ijms18010218.

Abstract

Heliopsis longipes 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 H. longipes 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 H. longipes 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 (NG-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 (1H-[1,2,4]oxadiazolo[4,3-a]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.

Keywords: Heliopsis longipes; affinin; gasotransmitters; prostacyclin; rat aorta; vasodilation.

MeSH terms

  • Amides / chemistry
  • Amides / isolation & purification*
  • Amides / pharmacology*
  • Animals
  • Aorta / drug effects
  • Aorta / physiology
  • Asteraceae / chemistry*
  • Cyclic AMP / metabolism
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiology
  • Epoprostenol / metabolism*
  • Gasotransmitters / metabolism*
  • Indomethacin / pharmacology
  • Male
  • Methylene Chloride
  • Models, Biological
  • Phytochemicals / pharmacology
  • Plant Extracts / pharmacology
  • Plant Roots / chemistry
  • Polyunsaturated Alkamides
  • Potassium Channels / metabolism
  • Rats, Wistar
  • Signal Transduction / drug effects*
  • Vasodilation / drug effects*

Substances

  • Amides
  • Gasotransmitters
  • N-isobutyl-2E-decenamide
  • Phytochemicals
  • Plant Extracts
  • Polyunsaturated Alkamides
  • Potassium Channels
  • Methylene Chloride
  • Epoprostenol
  • Cyclic AMP
  • Indomethacin