Treatment with an extract of Terminalia superba Engler & Diels decreases blood pressure and improves endothelial function in spontaneously hypertensive rats

Abstract

Ethnopharmacological relevance: 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.

Materials and 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.

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.