This study shows combination of cardiovascular activities exhibited by the crude extracts of Acorus calamus and Berberis vulgaris along with its fractions and two commercially available pure compounds of B. vulgaris, berberine and berbamine, which were selected, based on their medicinal use in cardiovascular disorders.
In rats under anesthesia, the crude extract of Berberis vulgaris (Bv.Cr) and its aqueous (Bv.Aq) and butanol (Bv.Btol) fractions along with berberine and berbamine caused fall in mean arterial pressure (MAP). In isolated rabbit aorta preparations, Bv.Cr inhibited phenylephrine (PE) and high K+-induced contractions, shifted the Ca++ concentration-response curves (CRCs) to the right and suppressed the PE peak formation, in Ca++ -free medium. When tested in isolated rabbit aorta preparations, Bv.Aq and Bv.Btol were similar to Bv.Cr except Bv.Btol that exhibited selective inhibitory effect against PE-induced contractions and showed alpha-adrenoceptor blocking activity. When tested on basal tension of rabbit aorta preparations, Bv.Cr and Bv.Btol exhibited vasoconstrictor effect.
Berberine was more potent in inhibiting PE than high K+ -induced contractions in isolated rabbit aorta preparations. It also shifted the Ca ++ CRCs to the right, suppressed PE peak formation, in Ca++ -free medium and exhibited a-adrenoceptor blockIng activity. Contrary to berberine, berbamine was more potent in inhibiting high K+ than PE-induced contractions as well as shifted the Ca++ CRCs to the right but was without effect on the PE peak formation. Both berberine and berbamine were without vasoconstrictor effect on baseline vascular tension.
In isolated rat aorta preparations, Bv.Cr and its fractions exhibited vascular relaxation mediated partially through endothelium-dependent (L-NAME sensitive nitric oxide (NO)-mediated) pathway and also inhibited high K+ -induced contractions. Berberine also exhibited partial endothelium-dependent (L-NAME sensitive NO-mediated). vasodilatory effect and partially inhibited high K+-induced contractions. Berbamine caused partial endothelium-independent vasodilatory effect while relatively more potent against high K+ -induced contractions.
In isolated bovine coronary arterial (BCA) rings, Bv.Btol exhibited endothelial-derived hyperpolarizing (EDHF)-mediated relaxant effect which is partially blocked in the presence of TEA, SKF525A or increasing K+ concentrations, similar to methacholine and arachidonic acid. Bv.Cr and Bv.Aq caused EDHF independent relaxant effect, with a vasoconstrictor effect exhibited by Bv.Aq. Berberine and berbamine also exhibited EDHF-mediated relaxant effect in BCA rings.
In isolated rabbit heart preparations, Bv.Cr and its fractions were more effective in inhibiting force of ventricular contraction (FVC), with partial inhibitory effect on heart rate (HR) and coronary flow (CF) except for Bv.Btol which caused a negligible increase in CF, similar to methacholine. Berberine caused partial inhibition of FVC and CF while less effective on HR.
In isolated guinea-pig right arterial preparations, BV.Cr and its fractions caused inhibition of force and rate of contractions, at relatively higher concentrations than that observed in vascular smooth muscle preparations, similar to papaverine. Berberine and berbamine were without effect on both force and rate of isolated guinea-pig atrial preparations.
The crude extract of Acarus calamus (Ac.Cr) and its nHexane (Ac.nHexane) and ethylacetate (Ac.EtAc) fractions caused fall in MAP. In isolated rabbit aorta preparations, Ac.Cr was more potent in inhibiting high K+ -induced contractions than PE as well as shifted the Ca++ CRCs to the right and suppressed PE peak formation in Ca++ -free medium. When tested on baseline tension, the Ac.Cr also showed vasoconstrictory effect. AC.EtAc was relatively more potent in inhibiting PE-induced contractions than high K+ as well as shifted the Ca++ CRCs to the right and suppressed PE peaks formation. Ac.nHexane was equipotent against PE and high K+-induced contractions as well as shifted the Ca++ CRCs to the right but was without effect on PE peak formation. Both fractions were found devoid of contractile effect on the baseline tension. In isolated rat aorta preparations, Ac.Cr exhibited endothelium-independent relaxant effect on PE-induced contractions and a less potent inhibitory effect against high K+ -induced contractions.
The Ac.EtAc exhibited a strong endothelium-dependent contractile effect on PE-induced contractions was less potent against high K+ similar to Ac.Cr. AC.nHexane caused endothelium-dependent (L-NAME-sensitive NO-medicated) relaxation on PE-induced contractions and ryanodine-sensitive contractile effect on the baseline tension and partially inhibited high K+ -induced contractions.
In BCA rings, Ac.Cr exhibited EDHF-mediated relaxant effect, which is partially blocked in the presence of TEA, SKF 525A or varying concentrations of K+. Among the fractions, Ac.nHexane exhibited EDHF-mediated relaxant effect, while . the Ac.EtAc was -independent of EDHF -mediated relaxant effect and was about 10 times more potent than the parent crude extract.
In isolated perfused rabbit heart preparations, Ac.Cr partially inhibited FVC, HR and CF. Among the fractions, AC.EtAc was more potent in inhibiting FVC and partially inhibited HR and CF. The AC.nHexane was similar to AC.EtAc in inhibiting FVC, HR but caused a mild increase in CF. Verapamil also caused suppression of FVC, HR and CF.
In isolated guinea-pig arterial preparations, Ac.Cr and its one fraction (Ac.EtAc) caused suppression of force and rate of contractions, at comparatively higher concentrations than in vascular smooth muscle preparations.
Thus this study shows that Berberis vulgaris and Acorus calamus possesses combination of cardiovascular effects mediated through multiple pathways, which include calcium channel blocking, a-adrenoceptors blocking, NO and EDHF mediated and this study may rationalize their medicinal use in cardiovascular disorders. The presence of vasoconstrictory effects may offset the excessive fall in BP and or vasodilatory effect of the crude extracts or their fractions. Additionally berberine and berbamine share some of the cardiovascular inhibitory properties of B. vulgaris, with berberine being relatively selective for a-adrenoceptors, where as berbamine more potent for its calcium antagonistic activity. These results further showed that though berberine showed most of the cardiovascular activities of the parent crude extract but it appears as no single compound can be a true representative of the parent plant which constitutes multiple compounds with different properties of assigned activities.