Neuroprotective effect of p-coumaric acid in rat model of embolic cerebral ischemia

Document Type: Original Article


1 Department of Neurosurgery, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey

2 Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey

3 Department of Pathology, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey

4 Department of Histology & Embryology, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey

5 Department of Pharmacology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey

6 Department of Physiology, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey


Objective(s): Stroke poses a crucial risk for mortality and morbidity. Our study aimed to investigate the effect of p-coumaric acid on focal cerebral ischemia in rats.
Material and Methods: Rats were randomly divided into four groups, namely Group I (control rats), Group II (ischemia rats), Group III (6 hr ischemia + p-coumaric acid rats) and Group IV (24 hr ischemia + p-coumaric acid rats). Cerebral ischemia was induced via intraluminal monofilament occlusion model. In all groups, the brain was removed after the procedure and rats were sacrificed. Malondialdehyde, superoxide dismutase and nuclear respiratory factor-1 were measured in the ischemic hemisphere. The histopathological changes were observed in the right hemisphere within the samples. Functional assessment was performed for neurological deficit scores.
Results: Following the treatment, biochemical factors changed significantly. Histopathologically, it was shown that p-coumaric acid decreased the oxidative damage. The neurological deficit scores of p-coumaric acid-treated rats were significantly improved after cerebral ischemia.
Conclusion:Our results showed that p-coumaric acid is a neuroprotective agent on account of its strong anti-oxidant and anti-apoptotic features. Moreover, p-coumaric acid decreased the focal ischemia. Extra effort should be made to introduce p-coumaric acid as a promising therapeutic agent to be utilized for treatment of human cerebral ischemia in the future.


1. Thong-asa W, Tilokskulchai K. Neuronal damage of the dorsal hippocampus induced by long-term right common carotid artery occlusion in rats. Iran J Basic Med Sci 2014; 17:220-226.

2. Simonyi A, Wang Q, Miller RL, Yusof M, Shelat PB, Sun AY, et al. Polyphenols in cerebral ischemia: novel targets for neuroprotection. Mol Neurobiol 2005; 31:135-147.

3. Kong CS, Jeong CH, Choi JS, Kim KJ, Jeong JW. Antiangiogenic effects of p-coumaric acid in human endothelial cells. Phytother Res 2013; 27:317-323.

4. King A, Young G. Characteristics and occurrence of phenolic phytochemicals. J Am Diet Assoc 1999; 99:213-218.

5. Luceri C, Giannini L, Lodovici M, Antonucci E, Abbate R, Masini E, et al. p-Coumaric acid, a common dietary phenol, inhibits platelet activity in vitro and in vivo. Br J Nutr 2007; 97:458-463.

6. Zang LY, Cosma G, Gardner H, Shi X, Castranova V, Vallyathan V. Effect of antioxidant protection by p-coumaric acid on low-density lipoprotein cholesterol oxidation. Am J Physiol Cell Physiol 2000; 279:954-960.

7. Luceri C, Guglielmi F, Lodovici M, Giannini L, Messerini L, Dolara P. Plant phenolic 4-coumaric acid protects against intestinal inflammation in rats. Scand J Gastroenterol 2004; 39:1128-1133.

8. Folwarczna J, Zych M, Burczyk J, Trzeciak H, Trzeciak HI. Effects of natural phenolic acids on the skeletal system of ovariectomized rats. Planta Med 2009; 75:1567-1572.

9. Seo YK, Kim SJ, Boo YC, Baek JH, Lee SH, Koh JS. Effects of p-coumaric acid on erythema and pigmentation of human skin exposed to ultraviolet radiation. Clin Exp Dermatol 2011; 36:260-266.

10. Hudson EA, Dinh PA, Kokubun T, Simmonds MS, Gescher A. Characterization of potentially chemo-preventive phenols in extracts of brown rice that inhibit the growth of human breast and colon cancer cells. Cancer Epidemiol Biomarkers Prev 2000; 9:1163-1170.

11. Vauzour D, Corona G, Spencer JP. Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity. Arch Biochem Biophys 2010; 501:106-111.

12. Abdel-Wahab MH, El-Mahdy MA, Abd-Ellah MF, Helal GK, Khalifa F, Hamada FM. Influence of p-coumaric acid on doxorubicin-induced oxidative stress in rat's heart. Pharmacol Res 2003; 48:461-465.

13. Jyoti Roy A, Stanely Mainzen Prince P. Preventive effects of p-coumaric acid on lysosomal dysfunction and myocardial infarct size in experimentally induced myocardial infarction. Eur J Pharmacol 2013; 699:33-39.

14. Prasanna N, Krishnan DN, Rasool M. Sodium arsenite-induced cardiotoxicity in rats: protective role of p-coumaric acid, a common dietary polyphenol. Toxicol Mech Methods 2013; 23:255-262.

15. Stanely Mainzen Prince P, Roy AJ. p-Coumaric acid attenuates apoptosis in isoproterenol-induced myocardial infarcted rats by inhibiting oxidative stress. Int J Cardiol 2013; 168:3259-3266.

16. Cho JY, Moon JH, Seong KY, Park KH. Antimicrobial activity of 4-hydroxybenzoic acid and trans 4-hydroxycinnamic acid isolated and identified from rice hull. Biosci Biotechnol Biochem 1998; 62:2273-2276.

17. Ferguson LR, Zhu ST, Harris PJ. Antioxidant and antigenotoxic effects of plant cell wall hydroxycinnamic acids in cultured HT-29 cells. Mol Nutr Food Res 2005; 49:585-593.

18. Janicke B, Onning G, Oredsson SM. Differential effects of ferulic acid and p-coumaric acid on S phase distribution and length of S phase in the human colonic cell line Caco-2. J Agric Food Chem 2005; 53:6658-6665.

19. Barros MP, Lemos M, Maistro EL, Leite MF, Sousa JP, Bastos JK, et al. Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis. J Ethnopharmacol 2008; 120:372-377.

20. Pragasam SJ, Murunikkara V, Sabina EP, Rasool M. Ameliorative effect of p-coumaric acid, a common dietary phenol, on adjuvant-induced arthritis in rats. Rheumatol Int 2013; 33:325-334.

21. Hata R, Mies G, Wiessner C, Fritze K, Hesselbarth D, Brinker G, et al. A reproducible model of middle cerebral artery occlusion in mice: hemodynamic, biochemical, and magnetic resonance imaging. J Cereb Blood Flow Metab 1998; 18:367-375.

22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265-275.

23. Durak I, Yurtarslanl Z, Canbolat O, Akyol O. A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin Chim Acta 1993; 214:103-104.

24. Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol 1978; 52:302-310.

25. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H. Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 1986; 17:472-476.

26. Yaman M, Eser O, Cosar M, Bas O, Sahin O, Mollaoglu H, et al. Oral administration of avocado soybean unsaponifiables (ASU) reduces ischemic damage in the rat hippocampus. Arch Med Res 2007; 38:489-494.

27. Lancelot E, Callebert J, Revaud ML, Boulu RG, Plotkine M. Detection of hydroxyl radicals in rat striatum during transient focal cerebral ischemia: possible implication in tissue damage. Neurosci Lett 1995; 197:85-88.

28. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 1995; 41:1819-1828.

29. White BC, Grossman LI, Krause GS. Brain injury by global ischemia and reperfusion: a theoretical perspective on membrane damage and repair. Neurology 1993; 43:1656-1665.

30. Bosca L, Hortelano S. Mechanisms of nitric oxide-dependent apoptosis: involvement of mitochondrial mediators. Cell Signal 1999; 11:239-244.

31. Braughler JM, Hall ED. Central nervous system trauma and stroke. I. Biochemical considerations for oxygen radical formation and lipid peroxidation. Free Radic Biol Med 1989; 6:289-301.

32. Gutsaeva DR, Carraway MS, Suliman HB, Demchenko IT, Shitara H, Yonekawa H, et al.Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism. J Neurosci 2008; 28:2015-2024.

33. Kumari S, Anderson L, Farmer S, Mehta SL, Li PA. Hyperglycemia alters mitochondrial fission and fusion proteins in mice subjected to cerebral ischemia and reperfusion. Transl Stroke Res 2012; 3:296-304.

34. Vauzour D, Vafeiadou K, Rice-Evans C, Williams RJ, Spencer JP. Activation of pro-survival Akt and ERK1/2 signalling pathways underlie the anti-apoptotic effects of flavanones in cortical neurons. J Neurochem 2007; 103:1355-1367.