title: Vasorelaxant and antihypertensive effects of methanolic extracts from Hymenocardia acida Tul.
abstract: BACKGROUND
  In Congolese traditional medicine, decoctions of Hymenocardia acida root bark (HaRB) and trunk bark (HaTrB) are used for the treatment of conditions assumed to be hypertension. In this work, we propose to study the vasorelaxant effect of HaRB and HaTrB methanolic extracts on isolated rat thoracic aorta, to characterize the group of molecules responsible for the observed vasorelaxant activity, to evaluate the in vitro antioxidant activity of these extracts and to determine the antihypertensive activity of the HaRB extract on spontaneously hypertensive rats (SHR).
  
  
  METHODS
  The vasorelaxant effect of the HaRB and HaTrB methanolic extracts was studied on endothelium-intact aortic rings pre-contracted with phenylephrine (PE, 1μM). The mechanism of this vasorelaxant effect was investigated on endothelium-denuded vessels and on endothelium-intact aortic rings in the presence of three inhibitors: l-N(G)-nitroarginine methyl ester (100μM), indomethacin (10μM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10μM). To determine the nature of the compounds responsible for the vasorelaxant activity, we carried out a fractionation of the extracts and a thiolysis of the most active fraction followed by a liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) analysis. The extracts antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) colorimetric assay. In vivo anti-hypertensive activity of the HaRB extract was conducted on SHR.
  
  
  RESULTS
  HaRB and HaTrB methanolic extracts produced a concentration-dependent vasorelaxation on intact aortic rings pre-contracted with PE (1μM). The vasorelaxant responses obtained were 95.3±1.5% (5μg/ml) and 100.6±3.0% (1μg/ml), respectively. The effect was markedly attenuated by removal of endothelium or pretreatment of aortic rings with all inhibitors except indomethacin. The LC/ESI-MS analysis of the thiolysis products indicated that the fraction which caused the most important vasorelaxation (97.9±2.5% at 3μg/ml) was a mixture of procyanidins and prodelphinidins, with a predominance of procyanidins. Both extracts and all fractions from HaRB extract showed a DPPH scavenging activity, ranging from 0.4 to 0.8 quercetin-equivalents. The HaRB methanolic extract reduced the systolic blood pressure in SHR (from 214±3mmHg to 194±4mmHg) after a 5-week treatment.
  
  
  CONCLUSIONS
  The methanolic extracts of Hymenocardia acida root and trunk bark have vasorelaxant activity. The vasorelaxant effect observed is endothelium-dependent and seems mainly mediated through the NO-cGMP pathway. The COX pathway is not involved. The vasorelaxant activity appears to be due to polymeric procyanidins and prodelphinidins. These extracts also have an antioxidant effect. The extract of Hymenocardia acida root bark shows a significant but weak antihypertensive activity in SHR.
authors: Laboratory of Physiology and Pharmacology, Faculty of Pharmacy, Université Libre de Bruxelles, CP 205/7, Bd du Triomphe, 1050 Brussels, Belgium.
authors: Francine
authors: F
authors: Nsuadi Manga
authors: Charaf
authors: C
authors: El Khattabi
authors: Jeanine
authors: J
authors: Fontaine
authors: Guy
authors: G
authors: Berkenboom
authors: Pierre
authors: P
authors: Duez
authors: Caroline
authors: C
authors: Noyon
authors: Pierre
authors: P
authors: Van Antwerpen
authors: José
authors: J
authors: Lami Nzunzu
authors: Stéphanie
authors: S
authors: Pochet
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D015023:Democratic Republic of the Congo; D006162:Guanylate Cyclase / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D066298:In Vitro Techniques; D019684:Magnoliopsida; D008297:Male; D016488:Medicine, African Traditional; D000432:Methanol / Q000737:chemistry; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018517:Plant Roots; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012997:Solvents / Q000737:chemistry; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D010936:Plant Extracts; D012997:Solvents; D014665:Vasodilator Agents; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D000432:Methanol