Antihypertensive and vasorelaxant activities of flavonoid glycosides from Ruta montana (L.) L. in rat

Species of the genus Ruta have attracted attention as a source of various classes of natural products with biological activities. This study aimed to evaluate the antihypertensive property of Ruta montana (L.) L. Flavonoid-glycosides enriched extract (RMFEE) in the Nω-Nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Each treated group received, the RMFEE (150 and 400 mg/kg), orally and the blood pressure (BP) parameters were measured. Additionally, the vasorelaxant activity of RMFEE (0.75, 1.50, 2.25 and 3.75 mg/mL) was evaluated in isolated thoracic aortic rings previously contracted with epinephrine (EP; 10-5 M) or potassium chloride (KCl; 80 mM). Moreover, to investigate the signalling pathways involved in RMFEE-induced vascular relaxation of aortic rings, we employed specific pathway inhibitors. The involvement of calcium channels in the vasodilator activity of plant RMFEE (0.50 and 1 mg/mL) was also assessed using a calcium-free Krebs-Henseleit (KH) buffer. In this investigation, a sub-chronic oral administration of RMFEE (400 mg/kg body weight) demonstrated a significant systolic blood pressure-lowering effect in L-NAME-induced hypertensive rats on the 4th and 7th days (p < 0.05 and p < 0.0001 respectively). Furthermore, aortic rings pre-contracted with PE or KCl were significantly relaxed by RMFEE (p < 0.0001 and p < 0.01 respectively). The present study demonstrates that RMFEE exhibits significant antihypertensive and vasorelaxant activities via the involvement of nitric oxide-cyclic guanosine monophosphate (NO-cGMP) and vascular prostaglandin pathways. Also, the inhibition of the receptor-operated calcium channels (ROCCs) may be implicated in this pharmacological effect.