Protective Effect of Apium graveolens L. (Celery) Seeds Extracts and Luteolin on Acetic Acid‑Induced Colitis in Rats

Mohsen Minaiyan, Seyed‑Mustafa Ghanadian, Melika Hossaini


Introduction: Anti‑oxidant, antispasmodic, anti‑inflammatory, and analgesic effects have been reported for Apium graveolens Linn. ) Celery( seeds and its active component luteolin. So, this study was carried out to investigate the protective effects of hexane (AGHE) and methanol (AGME) extracts of A. graveolens seeds and luteolin on acetic acid‑induced colitis in rats. Methods: Three doses of AGHE (100, 200, and 400 mg/kg), AGME (200, 400, and 800 mg/kg), and luteolin (5, 10, and 20 mg/kg) were administered orally (p.o.) to separate groups of male Wistar rats, 2 h before ulcer induction (acetic acid 4%) and continued once daily for 4 days. Prednisolone (4 mg/kg) and mesalazine (100 mg/kg) were used as reference and vehicle (2 mL/kg) as control groups. Colon biopsies were taken for weighting, macroscopic and histopathologic evaluation, and measuring myeloperoxidase (MPO) activity. Results: Our findings showed that AGHE (200 and 400 mg/kg), AGME (400 and 800 mg/kg), and luteolin (10 and 20 mg/kg) were effective to reduce colonic ulcer score, area, and index as well as total colitis index, and MPO activity significantly in comparison with controls. Since the lowest doses of extracts and luteolin were not significantly effective to diminish evaluated parameters of colitis, it is concluded that the ameliorative effect was dose related. Conclusion: It is also concluded that both extracts and luteolin, as an important ingredient of celery extract, were effective in the amelioration of colitis in rats, but further clinical and detailed mechanistic experiments are required to introduce these natural agents for colitis treatment or prevention in human.


Acetic acid; animal model; Apium graveolense; colitis; luteolin

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Syed‑Sufiyan F, Rajeev KS. Review on the pharmacognostical

and pharmacological characterization of Apium graveolens Linn.

Indo Glob J Pharm Sci 2012;2:36‑42.

Kooti W, Ali‑Akbari S, Asadi‑Samani M, Ghadery H,

Ashtary‑Larky D. A review on medicinal plant of

Apium graveolens. Adv Herb Med 2014;1:48‑59.

Ramezani M, Nasri S, Yassa N. Antinociceptive and

anti‑inflammatory effects of isolated fractions from

Apium graveolens seeds in mice. Pharm Biol 2009;47:740–3.

Kooti W, Daraei N. A review of the antioxidant activity of

celery (Apium graveolens L). J Evid Bas Compl Alt Med


Atta AH, Alkofahi A. Anti‑nociceptive and anti‑inflammatory

effects of some Jordanian medicinal plant extracts.

J Ethnopharmacol 1998;60:117–24.

Brankovic S, Gocmanac‑Ignjatovic M, Kostic M, Veljkovic M, Miladinovic B, Milutinovic M, et al. Spasmolytic activity of the

aqueous and ethanol celery leaves (Apium graveolens) extracts

on the contraction of isolated rat ileum. Acta Med Medianae


Al‑Howiriny T, Alsheikh A, Alqasoumi S, Al-Yahya M,

ElTahir K, Rafatullah S. Gastric antiulcer, antisecretory and

cytoprotective properties of celery (Apium graveolens) in rats.

Pharm Biol 2010;48:786–93.

Zargari A. Medicinal Plants. 5th ed. Tehran: Tehran University

Press; 1990. p. 476–82.

Evans WC. Trease and Evans Pharmacognosy. 15th ed. London:

Bailliere Tindall; 1996. p. 301‑7.

Zhou K, Zhao F, Liu Z, Zhuang Y, Chen L, Qiu F. Triterpenoids

and flavonoids from celery (Apium graveolens). J Nat Prod


Lin LZ, Lu S, Harnly JM. Detection and quantification of

glycosylated flavonoid malonates in celery, Chinese celery, and

celery seed by LC-DAD-ESI/MS. J Agric Food Chem. 2007;55:


Kumar Sh, Pandey AK. Chemistry and biological activities

of flavonoids: An overview. Sci World J 2013. doi:

1155/2013/162750. Lin LZ, Lu S, Harnly JM. Detection and

quantification of glycosylated flavonoid malonates in celery,

Chinese celery, and celery seed by LC‑DAD‑ESI/MS. J Agric

Food Chem 2007;55:1321‑6.

Nabavi SF, Braidy N, Gortzi O, Sobarzo‑Sanchez E, Daglia M,

Skalicka‑Wozniak K, et al. Luteolin as an anti‑inflammatory

and neuroprotective agent: A brief review. Brain Res Bull


Jeon I, Soo Kim H, Ju Kang H, Seo Lee H, Jeong S, Soo Kim J.

Anti‑Inflammatory and antipruritic effects of luteolin from

Perilla (P. frutescens L.) Leaves. Molecules 2014;19:6941‑51.

Loftus EV. Clinical epidemiology of inflammatory bowel

disease: Incidence, prevalence, and environmental influences.

Gastroenterology 2004;126:1504‑17.

Sellin JH, Pasricha PJ. Pharmacotherapy of inflammatory bowel

disease. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman

and Gilman’s the Pharmacological Basis of Therapeutics. 11th ed.

New York: McGraw Hill Companies; 2006. p. 1037‑56.

Sartor RB. Pathogenesis and immune mechanism of chronic

inflammatory bowel diseases. Am J Gastroenterol 1997;92:5‑11.

Robert W. Novel and future medical management of inflammatory

bowel disease. Surg Clin North Am 2007;87:727‑47.

McQuaid KR. Drugs used in the treatment of gastrointestinal

disease. In: Katzung BG, editor. Basic and Clinical Pharmacology.

th ed. New York: McGraw Hill Companies; 2007. p. 1009‑40.

Minaiyan M, Zolfaghari B, Kamal A. Effect of hydroalcoholic

and buthanolic extract of Cucumis sativus seeds on blood

glucose level of normal and streptozotocin‑induced diabetic rats.

Iran J Basic Med Sci 2011;14:436‑42.

Chandra S, Khan Sh, Avula B, Lata H, Yang MH, ElSohly MA,

et al. Assessment of total phenolic and flavonoid content,

antioxidant properties, and yield of aeroponically and

conventionally grown leafy vegetables and fruit crops:

A comparative study. Evid Based Complement Alternat Med

;2014:253875. doi: 10.1155/2014/253875.

Marinova D, Ribarova F, Atanassova M. Total phenolic and total

flavonoids in Bulgarian fruits and vegetables. J Univ Cheml

Technol Metal 2005;40:255–60.

Chang C, Yang M, Wen H, Chern J. Estimation of total flavonoid

content in propolis by two complementary color metric methods.

J Food Drug Anal 2002;10:178–82.

Mascolo N, Izzo A, Autore G, Maiello F, Dicarlo G, Capsso F.

Acetic acid‑induced colitis in normal and essential fatty acid

deficient rats. J Pharmacol Exp Ther 1995;272:469–75.

Mahdavi NS, Talebi A, Minaiyan M. Ameliorative effect of

galantamine on acetic acid‑induced colitis in rats. Res Pharm Sci


Sadraei H, Asghari G, Khanabadi M, Minaiyan M.

Anti‑inflammatory effect of apigenin and hydroalcoholic extract

of Dracocephalum kotschyi on acetic acid‑induced colitis in rats.

Res Pharm Sci 2017;12:322‑9.

Cooper HS, Murthy S, Shah R, Sedergan D. Clinicopathologic

study of dextran sulfate sodium experimental murine colitis.

Laboratory investigation. J Technic Meth Pathol 1993;69:238‑49.

Dieleman L, Palmen M, Akol H, Bloemena E, Pena A,

Meuwissen S. Chronic experimental colitis induced by dextran

sulfate sodium (DSS) is characterized by Th1 and Th2 cytokines.

Clin Exp Immuno 1998;114:385‑91.

Motavallian‑Naeini A, Minaiyan M, Rabbani M, Mahzuni P.

Anti‑inflammatory effect of ondansetron through 5‑HT3 receptors

on TNBS‑induced colitis in rat. EXCLI J 2012;11:30‑44.

Zabihi M, Hajhashemi V, Talebi A, Minaiyan M. Evaluation of

central and peripheral effects of doxepin on acetic acid‑induced

colitis in rat and the involved mechanisms. EXCLI J


Cominelli F, Arseneau KO, Rodriguez‑Palacios A, Pizarro T.

Uncovering pathogenic mechanisms of inflammatory bowel

disease using mouse models of Crohn’s disease–like ileitis: What

is the right model? Cell Mol Gastroenterol Hepatol 2017;4:19‑32.

Minaiyan M, Hajhashemi V, Rabbani M, Fattahian E,

Mahzouni P. Beneficial effects of maprotiline in a murine model

of colitis in normal and reserpinised depressed rats. Int Sch Res

Notices 2014. doi: 10.1155/2014/359841.

Shanmugapriya R, Ushadevi T. In vitro antibacterial and

antioxidant activities of Apium graveolens L. seed extracts. Int J

Drug Dev Res 2014;6:165‑70.

Podolsky DK. Inflammatory bowel disease. N Engl J Med


Ziyan L, Yongmei Z, Nan Z, Ning T, Baolin L. Evaluation of

the anti‑inflammatory activity of luteolin in experimental animal

models. Planta Med 2007;73:221‑6.

Minaiyan M, Sajjadi SE, Naderi N, Taheri D. Anti‑Inflammatory

effect of Kelussia odoratissima Mozaff. hydroalcoholic extract

on acetic acid‑ induced acute colitis in rats. J Reports Pharm Sci


Silvan AM, Abad MJ, Bermejo P, Villar A. Effect of compounds

extracted from Santolina oblongifolia on TBX (2) release in

human platelets. Inflammopharmacology 1998;6:255–63.

O’Leary KA, Pascual‑Treasa SD, Needs PW, Bao YP,

O’Brien NM, Williamson G. Effect of flavonoids and vitamin E on

cyclooxygenase‑2 (COX‑2) transcription. Mutation 2004;551:245–54.

Mencherini T, Cau A, Bianco G, Della Loggia R, Aquino RP,

Autore G. An extract of Apium graveolens var. dulce leaves:

Structure of the major constituent, apiin, and its anti‑ inflammatory

properties. J Pharm Pharmacol 2007;59:891–7.

Sultana S, Ahmed S, Jahangir T, Sharma S. Inhibitory effect of

celery seeds extract on chemically induced hepatocarcinogenesis:

Modulation of cell proliferation, metabolism and altered hepatic

foci development. Cancer Lett 2005;221:11–20.