Abstract
Celery (Apium graveolens L., Apiaceae) is one of the popular aromatic vegetables and part of the daily diet around the world. In this study, aqueous-ethanolic and hexane extracts of celery seed were prepared and the amount of n-butylphthalide, as an active component, was determined in each extract. Then the effects of hexanic extract on systolic, diastolic, mean arterial blood pressure and heart rate were evaluated in an invasive rat model. The vasodilatory effect and possible mechanisms of above mentioned extracts on aorta ring were also measured. High performance liquid chromatography analysis revealed that hexanic extract contains significantly higher amounts of n-butylphthalide, compared to aqueous-ethanolic extract. The results indicated that hexanic extract significantly decreased the systolic, diastolic, mean arterial blood pressure and heart rate in normotensive and hypertensive rats. Our data revealed that celery seed extract exerts its hypotensive effects through its bradycardic and vasodilatory properties. Moreover, the active components in celery seed extracts could induce their vasodilatory properties through Ca2+ channel blocking activity in endothelial and non-endothelial pathways and particularly by interference with the extra or intracellular calcium.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Alimohammadi, S., Hobbenaghi, R., Javanbakht, J., Kheradmand, D., Mortezaee, R., Tavakoli, M., Khadivar, F., Akbari, H., 2013. Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation. Diagn. Pathol. 8, 137.
Anjos, P.J., Lima, A.O., Cunha, P.S., De Sousa, D.P., Onofre, A.S., Ribeiro, T.P., Medeiros, I.A., Antoniolli, Â.R., Quintans-Júnior, L.J., Santos, M.R., 2013. Cardiovascular effects induced by linalool in normotensive and hypertensive rats. Z. Naturforsch. C 68, 181–190.
Bickerton, R.K., Buckley, J.P., 1961. Evidence for a central mechanism in angiotensin induced hypertension. Exp. Biol. Med. 106, 834–836.
Bogdanski, P., Suliburska, J., Szulinska, M., Stepien, M., Pupek-Musialik, D., Jablecka, A., 2012. Green tea extract reduces blood pressure, inflammatory biomarkers, and oxidative stress and improves parameters associated with insulin resistance in obese, hypertensive patients. Nutr. Res. 32, 421–427.
Branković, S., Kitić, D., Radenković, M., Veljković, S., Milica Kostić, M.B., Pavlović, D., 2010. Hypotensive and cardioinhibotory effects of the aqueous and ethanol extracts of celery (apium graveolens, apiaceae). Acta Med. Medianae 49, 13–16.
Bristow, M.R., 2000. β-Adrenergic receptor blockade in chronic heart failure. Circulation 101, 558–569.
Brown, M.J., Palmer, C.R., Castaigne, A., de Leeuw, P.W., Mancia, G., Rosenthal, T., Ruilope, L.M., 2000. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 356, 366–372.
Chatterjea, M., Shinde, R., 2012. Textbook of Medical Biochemistry. Wife Goes On.
Cheng, M.-C., Ker, Y.-B., Yu, T.-H., Lin, L.-Y., Peng, R.Y., Peng, C.-H., 2010. Chemical synthesis of 9 (Z)-octadecenamide and its hypolipidemic effect: a bioactive agent found in the essential oil of mountain celery seeds. J. Agric. Food Chem. 58, 1502–1508.
Dehkordi, F.R., Kamkhah, A.F., 2008. Antihypertensive effect of Nigella sativa seed extract in patients with mild hypertension. Fundam. Clin. Pharm. 22, 447–452.
Dimo, T., Nguelefack, T., Tan, P., Yewah, M., Dongo, E., Rakotonirina, S., Kamanyi, A., Bopelet, M., 2003. Possible mechanisms of action of the neutral extract from Bidens pilosa L. leaves on the cardiovascular system of anaesthetized rats. Phytother. Res. 17, 1135–1139.
Fazal, S.S., Singla, R.K., 2012. Review on the pharmacognostical and pharmacological characterization of Apium graveolens Linn. Indo Global J. Pharm. Sci. 2, 36–42.
Golalipour, M.J., Balajadeh, B.K., Ghafari, S., Azarhosh, R., Khori, V., 2011. Protective effect of Urtica dioica L. (Urticaceae) on morphometric and morphologic alterations of seminiferous tubules in STZ diabetic rats. Iran. J. Basic Med. Sci. 14, 472.
Kanter, M., Coskun, O., Korkmaz, A., Oter, S., 2004. Effects of Nigella sativa on oxidative stress and β-cell damage in streptozotocin-induced diabetic rats. Anat. Rec. A Discov. Mol. Cell. Evol. Biol. 279, 685–691.
Ko, F.-N., Huang, T.-F., Teng, C.-M., 1991. Vasodilatory action mechanisms of apigenin isolated from (Apium graveolens) in rat thoracic aorta. Biochim. Biopharm. Acta 1115, 69–74.
Kwon, Y.I., Apostolidis, E., Shetty, K., 2007. Evaluation of pepper (Capsicum annuum) for management of diabetes and hypertension. J. Food Biochem. 31, 370–385.
Li, R.-c., Cindrova-Davies, T., Skepper, J.N., Sellers, L.A., 2004. Prostacyclin induces apoptosis of vascular smooth muscle cells by a cAMP-mediated inhibition of extracellular signal-regulated kinase activity and can counteract the mitogenic activity of endothelin-1 or basic fibroblast growth factor. Circ. Res. 94, 759–767.
Mencherini, T., Cau, A., Bianco, G., Loggia, R.D., Aquino, R., 2007. An extract of Apium graveolens var. dulce leaves: structure of the major constituent, apiin, and its anti-inflammatory properties. J. Pharm. Pharmacol. 59, 891–897.
Modak, M., Dixit, P., Londhe, J., Ghaskadbi, S., Devasagayam, T.P.A., 2007. Indian herbs and herbal drugs used for the treatment of diabetes. J. Clin. Biochem. Nutr. 40, 163.
Moghadam, M.H., Imenshahidi, M., Mohajeri, S.A., 2013. Antihypertensive effect of celery seed on rat blood pressure in chronic administration. J. Med. Food 16, 558–563.
Mohajeri, S.A., Hosseinzadeh, H., Salami, S., Motamedshariaty, V., Seifi, M., Hadizadeh, F., 2011. Synthesis of novel 4-[1-(4-fluorobenzyl)-5-imidazolyl] dihydropyridines and studying their effects on rat blood pressure. Iran. J. Basic Med. Sci. 14, 451–457.
Momin, R., Nair, M., 2002. Antioxidant, cyclooxygenase and topoisomerase inhibitory compounds from Apium graveolens Linn. seeds. Phytomedicine 9, 312–318.
Moncada, S., Rees, D., Schulz, R., Palmer, R., 1991. Development and mechanism of a specific supersensitivity to nitrovasodilators after inhibition of vascular nitric oxide synthesis in vivo. Proc. Natl. Acad. Sci. U. S. A. 88, 2166–2170.
Niaz, K., Gull, S., Zia, M.A., 2013. Antihyperglycemic/hypoglycemic effect of celery seeds (ajwain/ajmod) in streptozotocin induced diabetic rats. J. Rawalpindi Med. Coll. 17, 134–137.
Pei, Z.-M., Murata, Y., Benning, G., Thomine, S., Klüsener, B., Allen, G.J., Grill, E., Schroeder, J.I., 2000. Calcium channels activated by hydrogen peroxide mediate abscisic acid signalling in guard cells. Nature 406, 731–734.
Peng, Y., Hu, Y., Xu, S., Li, P., Li, J., Lu, L., Yang, H., Feng, N., Wang, L., Wang, X., 2012. l-3-n-Butylphthalide reduces tau phosphorylation and improves cognitive deficits in AβPP/PS1-Alzheimer’s transgenic mice. J. Alzheimer’s Dis. 29, 379–391.
Peng, Y., Sun, J., Hon, S., Nylander, A.N., Xia, W., Feng, Y., Wang, X., Lemere, C.A., 2010. l-3-n-Butylphthalide improves cognitive impairment and reduces amyloid-β in a transgenic model of Alzheimer’s disease. J. Neurosci. 30, 8180–8189.
Powanda, M.C., Rainsford, K.D., 2011. A toxicological investigation of a celery seed extract having anti-inflammatory activity. Inflammopharmacology 19, 227–233.
Pushparaj, P.N., Tan, B.K.H., Tan, C.H., 2001. The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats. Life Sci. 70, 535–547.
Ramakrishna, V., Jailkhani, R., 2007. Evaluation of oxidative stress in insulin dependent diabetes mellitus (IDDM) patients. Diagn. Pathol. 2, 22–30.
Reinhart, K.M., Coleman, C.I., Teevan, C., Vachhani, P., White, C.M., 2008. Effects of garlic on blood pressure in patients with and without systolic hypertension: a meta-analysis. Ann. Pharmacother. 42, 1766–1771.
Sowbhagya, H., 2014. Chemistry, technology, and nutraceutical functions of celery (Apium graveolens L.): an overview. Crit. Rev. Food Sci. 54, 389–398.
Tan, B.K.H., Tan, C.H., Pushparaj, P.N., 2005. Anti-diabetic activity of the semi-purified fractions of Averrhoa bilimbi in high fat diet fed-streptozotocin-induced diabetic rats. Life Sci. 76, 2827–2839.
Tang, F.-f., Guo, J.-x., Zhang, J., Li, J., Su, M., 2007. Study on hypotensive and vasodilatory effects of celery juice. Food Sci. 28, 322–325.
Tang, J., Zhang, Y., Hartman, T.G., Rosen, R.T., Ho, C.T., 1990. Free and glycosidically bound volatile compounds in fresh celery (Apium graveolens L.). J. Agric. Food Chem. 38, 1937–1940.
Tanner, G.A., Tanner, J.A., 2001. Chronic caffeine consumption exacerbates hypertension in rats with polycystic kidney disease. Am. J. Kidney Dis. 38, 1089–1095.
Tsi, D., Tan, B., 1997. Cardiovascular pharmacology of 3-n-butylphthalide in spontaneously hypertensive rats. Phytother. Res. 11, 576–582.
Valdivielso, J.M., Macias, J.F., Lopez-Novoa, J.M., 1997. Cardiovascular effects of elgodipine and nifedipine compared in anaesthetized rats. Eur. J. Pharmacol. 335, 193–198.
van Bremen, T., Drömann, D., Luitjens, K., Dodt, C., Dalhoff, K., Goldmann, T., Schaaf, B., 2013. Triggering receptor expressed on myeloid cells-1 (Trem-1) on blood neutrophils is associated with cytokine inducibility in human E. coli sepsis. Diagn. Pathol. 8, 24.
Wiyakrutta, S., Sriubolmas, N., Panphut, W., Thongon, N., Danwisetkanjana, K., Ruangrungsi, N., Meevootisom, V., 2004. Endophytic fungi with anti-microbial, anti-cancer and anti-malarial activities isolated from Thai medicinal plants. World J. Microbiol. Biotechnol. 20, 265–272.
Zhou, K., Zhao, F., Liu, Z., Zhuang, Y., Chen, L., Qiu, F., 2009. Triterpenoids and flavonoids from celery (Apium graveolens). J. Nat. Prod. 72, 1563–1567.
Zhu, J., Zhang, Y., Yang, C., 2015. Protective effect of 3-n-butylphthalide against hypertensive nephropathy in spontaneously hypertensive rats. Mol. Med. Rep. 11, 1448–1454.
Zimmet, P., Alberti, K., Shaw, J., 2001. Global and societal implications of the diabetes epidemic. Nature 414, 782–787.
Author information
Authors and Affiliations
Corresponding author
Additional information
FTS contributed in extracting the celery seeds, HPLC analysis, running the in vivo experiments, analysis of the data, writing the manuscript, BMR supervised the ex vivo experiments, MI supervised the in vivo experiments, MD and HF contributed in ex vivo studies, YE contributed in vivo experiments and SAM designed the study, supervised the laboratory work, contributed to critical reading and editing of the manuscript as corresponding author. All the authors have read the final manuscript and approved the submission.
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Tashakori-Sabzevar, F., Razavi, B.M., Imenshahidi, M. et al. Evaluation of mechanism for antihypertensive and vasorelaxant effects of hexanic and hydroalcoholic extracts of celery seed in normotensive and hypertensive rats. Rev. Bras. Farmacogn. 26, 619–626 (2016). https://doi.org/10.1016/j.bjp.2016.05.012
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1016/j.bjp.2016.05.012