I= STUDIES ON THE CARDIOVASCULAR EFFECTS OF SELECTED INDIGENOUS MEDICINAL PLANTS
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Title of Thesis
STUDIES ON THE CARDIOVASCULAR EFFECTS OF SELECTED INDIGENOUS MEDICINAL PLANTS

Author(s)
ABDUL JABBAR SHAH
Institute/University/Department Details
Department of Pharmacology/ University of Karachi
Session
2007
Subject
Pharmacy
Number of Pages
189
Keywords (Extracted from title, table of contents and abstract of thesis)
cardiovascular effects, medicinal plants, acorus calamus, berberis vulgaris, berberine, berbamine, vasoconstrictory effects, vasodilatory effect, a-adrenoceptors

Abstract
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.

Download Full Thesis
35611.6 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
2445.46 KB
2 1 Introduction 1
4229.4 KB
  1.1 Historical Background Of Medicinal Plants 2
  1.2 Importance Of Research On Herbal Medicine 4
  1.3 Back To Nature And Perspective Of Herbal Research 7
  1.4 Use Of Medicinal Plants In Cardiovascular Disorders 8
  1.5 Regulation Of Cardiovascular Functions And Role Of Natural Products 12
3 2 Materials And Methods 19
2947.31 KB
  2.1 Drugs And Standards 20
  2.2 Animals 20
  2.3 Selection Of Plants 21
  2.4 Preparation Of The Crude Extract 21
  2.5 Fractionation Of The Crude Extract 21
  2.6 Preliminary Phytochemical Analysis 22
  2.7 Experimentations 23
  2.8 Data Analysis 34
4 3 Berberis Vulgaris 35
12380.95 KB
  3.1 Plant Details 36
  3.2 Summary Of The Work 36
  3.3 Background 38
  3.4 Berberine 40
  3.5 Berbamine 41
  3.6 Objective Of The Study 42
  3.7 Plant Material And Extraction Procedure 42
  3.8 Fractionation Of The Crude Extract 42
  3.9 Results 45
  3.10 Discussion 85
5 4 Acorus Calamus 106
13840.86 KB
  4.1 Plant Details 107
  4.2 Summary Of The Work 107
  4.3 Background 109
  4.4 Objective Of The Study 111
  4.5 Plant Material And Extraction Procedure 111
  4.6 Fractionation Of The Crude Extract 111
  4.7 Results 114
  4.8 Discussion 142
  4.9 Conclusion 153
  4.10 Bibliography 155