DOSE DEPENDENT EFFECTS OF CAFFEIC ACID PHENETHYL ESTER ON HEART RATE AND BLOOD PRESSURE IN RATS

Abstract

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Keywords

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DOSE DEPENDENT EFFECTS OF CAFFEIC ACID PHENETHYL ESTER ON HEART RATE AND BLOOD PRESSURE IN RATS

Abstract

Aim: Caffeic acid phenethyl ester (CAPE) is one of the major components of honeybee propolis and its structure is similar to flavonoids. The molecular mechanisms of the effects of CAPE on various systems including cardiovascular system have not been known well. The aim of the present study was to investigate the short term dose dependent in vivo cardiovascular effects including heart rate and blood pressure changes induced by CAPE in Sprague Dawley rats. Methods: The rats were anaesthetized and randomly divided into six groups (n:6 rats) as follows: the first two groups of rats were injected 0.9% NaCl or 10% alcohol; the other groups were injected 1 mg kg-1, 5 mg kg-1 10 mg kg-1 or 20 mg kg-1 CAPE i.v. Results: CAPE injection caused decrease in mean blood pressure (MBP) up to 20 sec. for 1 mg CAPE group and up to 2 min for 5 and 10 mg CAPE groups. On the other hand, heart rate (HR) was found to be decreased up to 10 min. for 10 mg CAPE group Conclusion: CAPE causes decrease in both HR and MBP and may affect conduction velocity and contractility in heart due to possible effects on neuronal transmission. Key words: Caffeic acid phenethyl ester (CAPE); bradycardia; hypotension; rat

Keywords

• Caffeic acid phenethyl ester (CAPE), bradycardia, hypotension, rat

References

1. Russo A, Longo R, Vanella A. Antioxidant activity of propolis: role of caffeic acid phenethyl ester and galangin. Fitoterapia 2002;73(Suppl 1):21-9
2. Burdock GA. Review of the biological properties and toxicity of bee propolis. Food Chem Toxicol 1998;36:347-63
3. Dobrowolski JW, Vohora SB, Sharma K et al. Antibacterial, antifungal, antiamoebic, antiinflammatory and antipyretic studies on propolis bee products. Ethnopharmacol 1991;35:77-82
4. Khayyal MT, el-Ghazaly MA, el- Khatib AS. Mechanisms involved in the antiinflammatory effect of propolis extract. Drugs Exp Clin Res 1993;19:197- 203
5. Ozen S, Akyol O, Iraz M et al. Role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin- induced nephrotoxicity in rats. J Appl Toxicol 2004;24:27-35
6. Ozyurt H, Sogut S, Yildirim Z et al. Inhibitory effect of caffeic acid phenethyl ester on bleomycine-induced lung fibrosis in rats. Clin Chim Acta 2004;339:65-75
7. Krol W, Scheller S, Czuba Z et al. Inhibition of neutrophils’ chemiluminescence by ethanol extract of propolis (EEP) and its phenolic components. Ethnopharmacol 1996;55:19-25
8. Michaluart P, Masferrer JL, Carothers AM et al. Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation. Cancer Res 1999;59:2347- 52

9. Borrelli F, Izzo AA, Di Carlo G et al. Effect of a propolis extract and caffeic acid phenethyl ester on formation of aberrant crypt foci and tumors in the rat colon. Fitoterapia 2002;73(Suppl 1):S38- 43
10. Chen YJ, Shiao MS, Wang SY. The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells. Anticancer Drugs 2001;12:143-914
11. Lee YJ, Liao PH, Chen WK, Yang CY. Preferential cytotoxicity of caffeic acid phenethyl ester analogues on oral cancer cells. Cancer Lett 2000;153:51-6
12. Park EH, Kahng JH. Suppressive effects of propolis in rat adjuvant arthritis. Arch Pharm Res 1999;22:554-855
13. Rossi A, Longo R, Russo A, Borrelli F, Sautebin L. The role of the phenethyl ester of caffeic acid (CAPE) in the inhibition of rat lung cyclooxygenase activity by propolis. Fitoterapia 2002;73(Suppl 1): S30-7
14. Natarajan K, Singh S, Burke TR Jr, Grunberger D, Aggarwal BB. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci U S A 1996;93:9090-5
15. Maffia P, Ianaro A, Pisano B et al. Beneficial effects of caffeic acid phenethyl ester in a rat model of vascular injury. Br J Pharmacol 2002;136:353-60
16. Ilhan A, Koltuksuz U, Ozen S, Uz E, Ciralik H, Akyol O. The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits. Eur J Cardiothorac Surg 1999;16: 458-63
17. Irmak MK, Fadillioglu E, Sogut S et al. Effects of caffeic acid phenethyl ester and alpha-tocopherol on reperfusion injury in rat brain. Cell Biochem Funct 2003;21: 283-9
18. Koltuksuz U, Ozen S, Uz E et al. Caffeic acid phenethyl ester prevents intestinal reperfusion injury in rats. J Pediatr Surg 1999;34:1458-62
19. Fadillioglu E, Oztas E, Erdogan H et al. Protective effects of caffeic acid phenethyl ester on doxorubicin-induced cardiotoxicity in rats. J Appl Toxicol 2004;24:47-52
20. Cicala C, Morello S, Iorio C, Capasso R, Borrelli F, Mascolo N. Vascular effects of caffeic acid phenethyl ester (CAPE) on isolated rat thoracic aorta. Life Sci 2003;73:73-80
21. Grunberger D, Banerjee R, Eisinger K et al. Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis. Experientia 1988;44:230-2
22. Paulino N, Dantas AP, Bankova V et al. Bulgarian propolis induces analgesic and anti-inflammatory effects in mice and inhibits in vitro contraction of airway smooth muscle. J Pharmacol Sci 2003;93: 307-13
23. Parker LC, Luheshi GN, Rothwell NJ, Pinteaux E. IL-1 beta signalling in glial cells in wildtype and IL-1RI deficient mice. Br J Pharmacol 2002;136:312-20
24. Fadillioglu E, Erdogan H, Sogut S, Kuku I. The effects of cafeic acid phenethyl ester on DNA-turnover rates and nitric oxide level in doxorubicin-induced myocardial injury. T Klin J Med Sci 2003;23:366-70
25. Song YS, Park EH, Hur GM, et al. Caffeic acid phenethyl ester inhibits nitric oxide synthase gene expression and enzyme activity. Cancer Lett 2002;175:53-61
26. Paton JF, Kasparov S, Paterson DJ. Nitric oxide and autonomic control of heart rate: a question of specificity. Trends Neurosci 2002;25:626-31
27. Motterlini R, Gonzales A, Foresti R, Clark JE, Gren CJ, Winslow RM. Heme oxygenase-1–derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo. Circ Res 1998;83:568-77
28. Johnson RA, Lavesa M, Askari B, Abraham NG, Nasjletti A. A heme oxygenase product, presumably carbon monoxide, mediates a vasodepressor function in rats. Hypertension 1995;25:166–9
29. Scapagnini G, Foresti R, Calabrese V et al. Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol 2002;61:554-61
30. Cassarino DS, Bennett JP Jr. An evaluation of the role of mitochondria in Mitochondrial mutations and oxidative pathology, protective nuclear responses, and cell death in neurodegeneration. Brain Res 1999;29:1–25 diseases:
31. Ozhan H, Akdemir R, Yazici M, Gunduz H, Duran S, Uyan C. Cardiac emergencies caused by honey ingestion: a single centre experience. Emerg Med J 2004;21:742-4
32. Onat FY, Yegen BC, Lawrence R, Oktay A, Oktay S. Mad honey poisoning in man and rat. Rev Environ Health 1991;9:3-9