Pharmacological basis for the medicinal use of polyherbal formulation and its ingredients in cardiovascular disorders using rodents

BACKGROUND: A compound herbal formulation (POL(4)) has been used in the indigenous system of medicine to treat cardiometabolic disorders like diabetes and associated hypertension. POL(4) and most of its constituents have not been studied widely for its therapeutic use in hypertension. This study is aimed to determine the efficacy and possible insight into mechanism(s) for the medicinal use of POL(4) and its ingredients in hypertension. METHODS: The aqueous methanolic extracts of POL(4) (POL(4).Cr) and its components [Cichorium intybus (Ci.Cr), Gymnema sylvestre (Gs.Cr), Nigella sativa (Ns.Cr) and Trigonella foenum graecum (Tfg.Cr)] were tested for blood pressure lowering activity in anaesthetized Sprague-Dawley rats. To assess the vasomodulatory effect, isolated tissue experiments were performed on rat aortic strips using isometric force transducer coupled with PowerLab data acquisition system. RESULTS: Administration of POL(4) to rats caused a dose-dependent (1–100 mg/kg) fall in mean arterial pressure (MAP) with maximum effect of 85.33 ± 1.76% at 100 mg/kg, similar to the effect of verapamil. All ingredients of POL(4) also decreased blood pressure with varying efficacy in following order Ns.Cr ≅ Ci.Cr > Tfg.Cr > Gs.Cr. In rat aortic preparations, POL(4) and its ingredients inhibited K(+) (80 mM)-induced contractions, Ci.Cr was the most potent followed by Ns.Cr > Tfg.Cr > Gs.Cr ≅ POL(4). Against phenylephrine (P.E) contractions, Ci.Cr and Tfg.Cr exhibited complete relaxation, while POL(4).Cr, Gs.Cr and Ns.Cr showed vasomodulatory effect. The Ca(++) antagonist activity was confirmed when POL(4) and its ingredients shifted Ca(++) concentrations-response curves to the right in a manner similar to that of verapamil. On baseline of rat aorta, the parent formulation and its ingredients (except Tfg.Cr) exhibited partially phentolamine (1 μM)-sensitive vasoconstriction. CONCLUSION: These data show that POL(4) and its constituents possess blood pressure lowering activity mediated through inhibition of Ca(++) influx via membranous Ca(++) channels and receptor (α-adrenergic) operated pathways. Thus, this study provides a rationale to the medicinal use of POL(4) and its constituents in hypertension.