title: Treatment with an extract of Terminalia superba Engler & Diels decreases blood pressure and improves endothelial function in spontaneously hypertensive rats.
abstract: BACKGROUND
  The stem bark of Terminalia superba (TS) is widely used as a decoction by Cameroonian folk medicine for the treatment of hypertension. The aim of the present study was to evaluate the effect of a chronic treatment with a TS extract on spontaneously hypertensive rats (SHR) with respect to efficacy, biochemical mechanisms and safety.
  
  
  METHODS
  Eleven-week-old SHR and normotensive Wistar Kyoto rats (WKY) were daily treated by gavage with a methylene chloride extract of stem bark of Terminalia superba (TMSE, 150mg/kg) or with the vehicle for 5 weeks. Systolic blood pressure (SBP) was measured weekly using the tail-cuff method. At the end of the treatment period, vascular function was assessed on isolated thoracic rings, urinary 8-iso-PGF2α levels were measured and cytochrome P-450 3A (CYP 3A) activity was evaluated in liver microsomes.
  
  
  RESULTS
  TMSE reduced SBP (P<0.001) in SHR but not in WKY rats. In SHR, the vasorelaxant response to acetylcholine was significantly improved by TMSE as a result of increased nitric oxide synthase (NO) activity and decreased superoxide anion production. In addition, TMSE reduced the vasoconstrictive effect of phenylephrine and improved the sensitivity of smooth muscle cells to NO. TMSE dramatically decreased 8-iso-PGF2α levels in SHR. By contrast, TMSE did not affect all these parameters in WKY rats. Neither diuresis nor the hepatic CYP 3A activity was modified in both animal groups.
  
  
  CONCLUSIONS
  This study demonstrated that Terminalia superba has a potent antihypertensive activity in SHR which is partly due to endothelium-dependent and endothelium-independent effects as well as decreased oxidative stress. The data also provide evidence for the lack of herb-drug interaction through hepatic CYP 3A.
authors.affiliation: EA 4267 Fonctions et Dysfonctions Epithéliales, Faculté de Médecine-Pharmacie, 19 rue Ambroise Paré, 25030 Besançon, France; Laboratoire de Physiologie Animale, Département des Sciences Biologiques, Ecole Normale Supérieure, B.P. 3805 Yaoundé, Cameroun.
authors.forename: Esther Ngo Lemba
authors.initials: EN
authors.lastname: Tom
authors.affiliation: EA 4267 Fonctions et Dysfonctions Epithéliales, Faculté de Médecine-Pharmacie, 19 rue Ambroise Paré, 25030 Besançon, France.
authors.forename: Corine
authors.initials: C
authors.lastname: Girard-Thernier
authors.affiliation: EA 4267 Fonctions et Dysfonctions Epithéliales, Faculté de Médecine-Pharmacie, 19 rue Ambroise Paré, 25030 Besançon, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Martin
authors.affiliation: Laboratoire de Physiologie Animale, Département de Biologie et Physiologie Animale, Faculté des Sciences, B.P. 812 Yaoundé, Cameroun.
authors.forename: Théophile
authors.initials: T
authors.lastname: Dimo
authors.affiliation: EA 4267 Fonctions et Dysfonctions Epithéliales, Faculté de Médecine-Pharmacie, 19 rue Ambroise Paré, 25030 Besançon, France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Alvergnas
authors.affiliation: EA 4267 Fonctions et Dysfonctions Epithéliales, Faculté de Médecine-Pharmacie, 19 rue Ambroise Paré, 25030 Besançon, France.
authors.forename: Maude
authors.initials: M
authors.lastname: Nappey
authors.affiliation: EA 4267 Fonctions et Dysfonctions Epithéliales, Faculté de Médecine-Pharmacie, 19 rue Ambroise Paré, 25030 Besançon, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Berthelot
authors.affiliation: EA 4267 Fonctions et Dysfonctions Epithéliales, Faculté de Médecine-Pharmacie, 19 rue Ambroise Paré, 25030 Besançon, France. Electronic address: cdemouge@univ-fcomte.fr.
authors.forename: Céline
authors.initials: C
authors.lastname: Demougeot
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000494:pharmacology; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013113:Spin Labels; D029766:Terminalia / Q000737:chemistry*
chemical_list: D003497:Cyclic N-Oxides; D010936:Plant Extracts; D013113:Spin Labels; D000109:Acetylcholine; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester
keywords: 8 isoprostaglandin F(2α); 8-iso-PGF(2α); ACh; CYP 3A; Diet; Drug interaction; Endothelial function; KCl; N(W)-nitro-l-arginine methyl ester; NO; NOS; Oxidative stress; PE; SBP; SHR; SNP; Spontaneously hypertensive rats; TMSE; Terminalia superba; Terminalia superba methylene chloride extract; VSMCs; WKY; Wistar Kyoto rats; acetylcholine; cytochrome P 450 3A; l-NAME; nitric oxide; nitric oxide synthase; phenylephrine; potassium chloride; sodium nitroprusside; spontaneously hypertensive rats; systolic blood pressure; vascular smooth muscle cells