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Biological Abstracts/Biosis, Chemical Abstracts, ... Flora SJS, Gwalior ... extract of Euphorbia prostrata ait on Shigella dysenteriae type 1-induced diarrhea in rats: ... on two consecutive occasions, the names of such members will be deleted.

Indian Journal of Pharmacology

ISSN 0253-7613

Official Publication of the Indian Pharmacological Society October 2007

Vol 39

Issue 5

Indexed / Listed in Science Citation Index, Journal Citation Report, Biological Abstracts/Biosis, Chemical Abstracts, EMBASE/Excerpta Medica, CAB Abstract, Global Health, Excerpta Medicinal and Aromatic Plants Abstracts, Health & Wellness Research Center, Health Reference Center Academic, InfoTrac One File, Expanded Academic ASAP, NCI Current Contents, Indian Science Abstracts, IndMed, and MedInd.

Chief Editor Shiv Prakash Executive Editor R. K. Dikshit Associate Editor

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Indian Journal of Pharmacology, The Chambers, 3 floor, Sarkhej - Gandhinagar Highway, Bodakdev, Ahmedabad - 380054, India. Tel: 079-26853419, 26840348, 26840427 Fax: 079 - 26853415 Website: www.ijp-online.com E-mail: [email protected] rd

258

Indian Journal of Pharmacology

ISSN 0253-7613

Official Publication of the Indian Pharmacological Society October 2007 Vol 39 Issue 5 CONTENTS

Editorial Irrational combinations: No consideration for patient safety: Shiv Prakash

217

Review Article Bioequivalence: Issues and perspectives: Shubha Rani

218

Research Papers Isolation, characterization and study of enhancing effects on nasal absorption of insulin in rat of the total saponin from Acanthophyllum squarrosum: S.A. Sajadi Tabassi, H. Hosseinzadeh, M. Ramezani, E. Moghimipour, S.A. Mohajeri

226

Pharmacological and biochemical evidence for the antidepressant effect of the herbal preparation Trans-01: Md. Shalam, S.M. Shantakumar, M. Laxmi Narasu

231

Effects of dexamethasone and betamethasone as COX-2 gene expression inhibitors on rigidity in a rat model of Parkinson’s disease: Mehdi Shafiee Ardestani, Hassan Mehrab, Nourallah Sadeghzadeh

235

Activity of aqueous ethanol extract of Euphorbia prostrata ait on Shigella dysenteriae type 1-induced diarrhea in rats: Kamgang René, Gonsu Kamga Hortense, Wafo Pascal, Mbungni N. Jean Alexis, Pouokam Ervice Vidal, Fokam Tagne Michel Archange, Fonkoua Marie Christine

240

Antidiarrheal and antimicrobial activities of Stachytarpheta jamaicensis leaves: S. Sasidharan, L. Yoga Latha, Z. Zuraini, S. Suryani, S. Sangetha, L. Shirley

245

Research Letters Positive inotropic and chronotropic effect of aloe gel on isolated rat heart: Pradeep Kumar, Manish Goyal, Sunita Tewari

249

Synergistic effect of cefixime and cloxacillin combination against common bacterial pathogens causing community acquired pneumonia: Astha Agarwal, N. Jain, A. Jain

251

In vitro cytotoxic and human recombinant caspase inhibitory effect of Annona reticulata leaves: Susanta Kumar Mondal, Nirup Bikash Mondal, Upal Kanti Mazumder

253

Correspondence Counterfeit and substandard drugs: The need for an effective and stringent regulatory control in India and other developing countries: A. Sukhlecha

255

Letter to the Editor Postgraduate education in medical pharmacology: A student’s viewpoint: Varun Gupta

256

Book Review

257

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259

Research Letter

Positive inotropic and chronotropic effect of aloe gel on isolated rat heart Aloe vera (Aloe barbadenesis), an indigenous medicinal plant[1] of family Liliaceae, is widely distributed in Asia, Africa and other tropical areas. It has been used in folk medicine for the treatment of skin ailments, including burns and wound healing.[2] It has lipid lowering[3] and hypotensive[4] actions and also reduces the frequency of anginal attacks.[5] A recent study has reported that aloe is a strong antioxidant and has free radical scavenging properties.[6] We hypothesized that aloe contains some cardioactive substance. To the best of our knowledge, the effect of aloe on isolated heart preparation has not been investigated. The objective of this study was to elucidate the effect of aloe on isolated heart. An aqueous solution of aloe was prepared by taking 1 gm of gel from the leaf of the aloe plant and dissolving it in 10 ml of distilled water; this solution was centrifuged at 3000 rpm for 15 min and the supernatant was filtered and used for the study. The Institutional Ethics Committee approved the study and all efforts were made to minimize animal suffering and to reduce the number of animal used. A total of 12 albino rats (150200 gm), procured from Central Drug Research Institute (CDRI), Lucknow, were randomly divided into two groups (control and experimental) of six rats each. The animals were anaesthetized with thiopental sodium, 25 mg/kg body weight, intraperitonially. Hearts were exposed through a left thoracotomy and the pericardium was removed. Heparin (1000 IU) was injected into the ventricles and the hearts were quickly removed and placed in ice-cold Krebs-Henseleits solution of pH 7.4, containing NaCl (118.0 mmol/l), KCl (4.7 mmol/l), CaCl2 (2.5 mmol/l), MgSO4 (1.0 mmol/l), KH2PO4 (1.0 mmol/l), glucose (11.0 mmol/l) and NaHCO3 (25.0 mmol/l). The hearts were thoroughly washed with ice-cold Kreb’s solution and then perfused according

to non-recirculating Langendroff technique. Kreb’s solution, equilibrated with 95% O2 + 5% CO2, was delivered through an aortic cannula at 37°C under a constant pressure of 60 mm Hg. Following perfusion, the hearts started beating spontaneously. All the hearts were perfused for 15 min to allow stabilization. Basal heart rate, the rate after each intervention and the force of contraction were recorded on a physiograph (Bio Device, Ambala, India); coronary flow per minute was recorded by collecting the coronary effluent. The hearts of the experimental group were perfused with an aqueous solution of Aloe in doses of 100 mg, 200 mg and 300 mg per liter of Kreb’s solution. The hearts were perfused with Kreb’s solution to wash the preparation after each intervention. Propranolol (1 µmol/l) was infused with Kreb’s solution in both groups and aloe solution, 300 mg/l, was infused in the experimental group. Data were analyzed using Student’s t test; P < 0.05 was taken as indicating a significant difference. Observation showed that in the aqueous solution, aloe at a dosage of 200 mg/l and 300 mg/l of Kreb’s solution significantly (P < 0.01) increased the heart rate, force of contraction and coronary flow in the hearts of the experimental group and the effect persisted during the continuous infusion over 10 min. Aloe vera at a dose of 100 mg/l did not show any effect (P > 0.05); aloe at a dose of 300 mg/l, when administered along with propranolol (10–6 mol/l), did not show any significant effect. In the present study, the increase in the hemodynamic parameters is associated with aloe vera infusion and is dose dependant [Table 1]. In the isolated heart preparation, increase in heart rate and force of contraction is due to sympathetic discharge of noradrenalin[7] and the effect is mediated via β2 receptors in the myocardium. In our study, the effect is blocked by propranolol, which suggests that the active ingredient

Table 1 Effect of aloe on hemodynamic parameters Groups Control Treatment with aloe vera (experimental group) Treatment with propranolol (control) Treatment with propranolol and aloe vera 300 mg/l

n=6 100 mg/l 200 mg/l 300 mg/l 10–6 mol/l 10–6 mol/l

Contractile force (in mm) 10.50 ± 1.04 10.0 ± 0.89 14.50 ± 0.89 15.83 ± 1.57 12.16 ± 1.16 12.00 ± 1.09

Coronary flow (ml/min) 4.63 ± 0.13 4.85 ± 0.18 6.48 ± 0.40 9.41 ± 0.26 5.16 ± 0.45 5.68 ± 0.45

Heart rate (Beats/min) 140.50 ± 4.03 140.5 ± 3.98 152.16 ± 2.92 172.50 ± 2.50 143.80 ± 1.72 149.0 ± 2.09

P < 0.05 Control: treatment group, P > 0.05 Propranolol treated: propranolol and aloe treated

Indian J Pharmacol

| October 2007 | Vol 39 | Issue 5 | 249-250

249

Kumar et al.: Positive inotropy induced by aloe gel

present in aloe vera may be acting either on the β-receptors or any other receptors that are blocked by propranolol. Further research is needed to rule out the possibility that the aloe solution could be responsible for stimulation of sympathetic nerve endings present in the myocardium. In the coronary arteries β-adrenergic receptors mediate vasodilatation. Activity in the noradrenergic nerves to the heart and injection of norepinephrine causes coronary vasodilatation. In our study it seems that increase in coronary flow is either due to accumulation of metabolites that may cause coronary vasodilatation or due to some substance present in aloe vera acting on β-adrenergic receptors. The active ingredients in aloe gel are amino acids, enzymes, minerals, vitamins and glycoside (saponins). [8] With this preliminary study, we are not able to identify the ingredients which is responsible for the positive inotropic and chronotropic effect on isolated heart. Aloe vera is reported to be useful in wound healing, asthma and anginal attacks and has lipid lowering, hypotensive and antioxidants properties.[2-6] To the best of our knowledge, this is the first report to show the effect of Aloe gel on isolated heart preparation. We conclude that in the future Aloe gel may find use in the treatment of congestive heart failure.

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Indian J Pharmacol

| October 2007 | Vol 39 | Issue 5 | 249-250

Pradeep Kumar, Manish Goyal, Sunita Tewari Department of Physiology, K.G. Medical University, Lucknow, India. E-mail: [email protected]

References 1. 2. 3. 4. 5. 6. 7. 8.

Anshoo G, Singh S, Kulkarni AS, Pant SC, Vijayaraghavan R, Protective effect of Aloe vera L. gel against sulphur mustard-induced systemic toxicity and skin lesions. Indian J Pharmacol 2005;37:103-10. Kaufman T, Kalderon N, Ullmann Y, Berger J. Aloe vera gel hindered wound healing of experimental second-degree burns: A quantitative controlled study. J Burn Care Rehabil 1988;9:156-9. Rajasekaran S, Ravi K, Sivagnanam K, Subramanian S. BeneÞcial effects of Aloe vera leaf gel extract on lipid proÞle status in rats with streptozocine diabetes. Clin Exp Pharmacol Physiol 2006;33:232-7. Saleem R, Fazi S, Siddiqui BS, Ahmed M, Hussain SA, Qazi A, et al. Hypotensive effect of chemical constituents from Aloe barbadenisis. Planta Med 2001;67: 757-60. Agarwal OP. Prevention of atheromatous heart disease. Angiology 1985;36: 485-92. Rajasekaran S, Sivagnanam K, Subramanian S. Antioxidant effect of Aloe vera gel extract in streptozotocin-induced diabetes in rats. Pharmacol Rep 2005;57:90-6. Dampney RA. Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 1994;74:323-64. Vogler BK, Ernst E. Aloe vera: A systemic review of its clinical effectiveness. Br J Gen Pract 1999;49:823-8.