Marjoram oil attenuates oxidative stress and improves colonic epithelial barrier function in dextran sulfate sodium-induced ulcerative colitis in Balb/c mice

Main Article Content

Bouayad DI
Hadria Grar
Sadia Berzou
Omar Kheroua
Djamel Saidi
Hanane Kaddouri


dextran sulfate sodium, experimental colitis, Origanum majorana, oxidative stress, inflammation, Ussing chamber


In this study, we explored the effects of marjoram oil (MO) on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Marjoram oil was found to significantly reduce the severity of DSS-induced colonic inflammation, as reflected by improved disease activity index, prevented colon length shortening, lower histopathological score, decreased myeloperoxidase activity, and reduced interlukin 6 (IL-6) levels. Moreover, marjoram oil pretreatment enhanced the colonic epithelial integrity by decreasing paracellular permeability. Marjoram oil was found to clearly reduce the colonic levels of thiobarbituric acid reactive substances assay and enhance the activity of superoxide dismutase, catalase, and glutathione sulfhydryl content. Marjoram oil could exert a protective effect on ulcerative colitis through its anti-inflammatory and antioxidant properties.

Abstract 18 | PDF Downloads 10 HTML Downloads 6 XML Downloads 4


Aebi, H. 1984. Catalase in vitro. Methods Enzymol. 105:121–126. 10.1016/S0076-6879(84)05016-3

Al Dhaheri, Y., Attoub, S., Arafat, K., Abuqamar, S., Viallet, J., Saleh, A., Al Agha, H., Eid, A. and Iratni, R. 2013. Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly metastatic human breast cancer cells: Inhibition of NF_B signaling and reduction of nitric oxide production. PLoS One 8(7):e68808. 10.1371/journal.pone.0068808

Al-Howiriny, T., Alsheikh, A., Alqasoumi, S., Al-Yahya, M., El Tahir, K. and Rafatullah, S. 2009. Protective effect of Origanum majorana L. “marjoram” on various models of gastric mucosal injury in rats. Am. J. Chin. Med. 37(3):531–545. 10.1142/s0192415x0900703x

Amirshahrokhi, K., Bohlooli, S. and Chinifroush, M.M. 2011. The effect of methylsulfonylmethane on the experimental colitis in the rat. Toxicol Appl Pharmacol. 253(3):197–202. 10.1016/j.taap.2011.03.017

Arranz, E., Jaime, L., López de las Hazas, M.C., Reglero, G. and Santoyo, S. 2015. Supercritical fluid extraction as an alternative process to obtain essential oils with anti-inflammatory properties from marjoram and sweet basil. Indu Crops Prod. 67:121–129. 10.1016/j.indcrop.2015.01.012

Athamneh, K., Alneyadi, A., Alsamri, H., Alrashedi, A., Palakott, A., El-Tarabily, K.A., Eid, A.H., Al Dhaheri, Y. and Iratni, R. 2020. Origanum majorana essential oil triggers p38 MAPK-mediated protective autophagy, apoptosis, and caspase-dependent cleavage of P70S6K in colorectal cancer cells. Biomolecules. 10(3):412. 10.3390/biom10030412

Baakhtari, S., McCombie, A., BokkelHuinink, S., Irving, P., Siegel, C.A., Mulde, R., Mulder, C.J. and Gearry, R. 2018. Observational study of perspectives of inflammatory bowel disease patients concerning the use of corticosteroids. Dig Dis (Basel). 36(1):33–39. 10.1159/000478772

Bang, B. and Lichtenberger, L.M. 2016. Methods of inducing inflammatory bowel disease in mice. Curr Protoc Pharmacol. 72(5):1–42. 10.1002/0471141755.ph0558s72

Benhalilou, N., Alsamri, H., Alneyadi, A., Athamneh, K., Alrashedi, A., Altamimi, N., Al Dhaheri, Y., Eid, A.H. and Iratni, R., 2019. Origanum majorana ethanolic extract promotes colorectal cancer cell death by triggering abortive autophagy and activation of the extrinsic apoptotic pathway. Front Oncol. 9:795. 10.3389/fonc.2019.00795

Bhattacharyya, A., Chattopadhyay, R., Mitra, S. and Crowe, S.E. 2014. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev. 94(2):329–354. 10.1152/physrev.00040.2012

Bouayad Debbagh, I., Grar, H., Saidi, D., Kheroua, O. and Kaddouri, H. 2021. Phytochemical analysis and in vitro antioxidant activities of marjoram oil. Biosci Res. 18(4):2888–2894.

Catanzaro, D., Rancan, S., Orso, G., Dall’Acqua, S., Brun, P., Giron, M.C., Carrara, M., Castagliulo, I., Ragazzi, E., Caparrotta, L. and Montopoli, M. 2015. Boswellia serrata preserves intestinal epithelial barrier from oxidative and inflammatory damage. PLoS One. 10(5):e0125375. 10.1371/Fjournal.pone.0125375

Cheifetz, AS., Gianoti, R., Luber, R and Gibson, P.R. 2017. Complementary and alternative medicines used by patients with inflammatory bowel diseases. Gastroenterology. 152(2):415–429. 10.1053/j.gastro.2016.10.004

Cooper, H.S., Murthy, S.N., Shah, R.S. and Sedergran, D.J. 1993. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 69(2):238–249. PMid: 8350599.

Della Pepa, T., Elshafie, H.S., Capasso, R., DeFeo, V., Camele, I., Nazzaro, F., Scognamiglio, M.R. and Caputo, L. 2019. Antimicrobial and phytotoxic activity of Origanum heracleoticum and O. majorana essential oils growing in Cilento (Southern Italy). Molecules. 24(14):2576. 10.3390/molecules24142576

Duletic, S., Alimpi´cAradski, A., Kolarevic, S., Vuković-Gačić, B., Oaldje, M., Živkovi´c, J., Šavikin, K. and Marin, P. 2018. Antineurodegenerative, antioxidant and antibacterial activities and phenolic components of Origanum majorana L. (Lamiaceae) extracts. J Appl Bot Food Qual. 91:126–134. 10.5073/JABFQ.2018.091.018

Erenler, R., Sen, O., Aksit, H., Demirtas, I., Yaglioglu, A.S., Elmastas, M. and Telci, I. 2016. Isolation and identification of chemical constituents from Origanum majorana and investigation of antiproliferative and antioxidant activities. J Sci Food Agric. 96(3):822–836. 10.1002/jsfa.7155

Guerra-Boone, L., Alvarez-Roman, R. and Salazar-Aranda, R. 2015. Antimicrobial and antioxidant activities and chemical characterization of essential oils of Thymus vulgaris, Rosmarinus officinalis, and Origanum majorana from northeastern Mexico. Pak J Pharm Sci. 28(1):363–369. PMid: 2563151421.

Goel, P. and Vasudeva, N. 2015. Origanum majorana L.–phyto-pharmacological review. Indian J Nat Prod Res. 6:261–267.

Goyal, N., Rana, A., Ahlawat, A., Bijjem, K.R.V. and Kumar, P. 2014. Animal models of inflammatory bowel disease. Rev Inflammopharmacol. 22(4):219–233. 10.1007/s10787-014-0207-y

Helieh, O., Cheresa, T., Willem, J.S. and Villiers, D. 2013. Green tea polyphenols and sulfasalazine have parallel anti-inflammatory properties in colitis models. Front Immunol. 5(4):132. 10.3389/fimmu.2013.00132

Iba, Y., Sugimoto, Y., Kamei, C. and Masukawa, T. 2003. Possible role of mucosal mast cells in the recovery process of colitis induced by dextran sulfate sodium in rats. Int Immunopharmacol. 3(4):485–491. 10.1016/s1567–5769(02)00299-0

Kitajima, S., Takuma, S. and Morimoto, M. 1999. Changes in colonic mucosal permeability in mouse colitis induced with dextran sulfate sodium. Exp Anim. 48(3):137–143. 10.1538/expanim.48.137

Klebanoff, S.J. 2005. Myeloperoxidase: friend and foe. J Leukoc Bio. 77(5):598–625. 10.1189/jlb.1204697

Kokkinidis, D.G., Bosdelekidou, E.E. and Iliopoulou, S.M. 2017. Emerging treatments for ulcerative colitis: a systematic review. Scand J Gastroenterol. 52(9):923–931. 10.1080/00365521.2017.1326163

Landy, J., Ronde, E., English, N., Clark, S.K., Hart, A.L., Knight, S., Ciclitira, P. J. and Al-Hassi, H.O. 2016. Tight junctions in inflammatory bowel diseases and inflammatory bowel disease associated colorectal cancer. World J. Gastroenterol. 22(11):3117–3126. 10.3748/wjg.v22.i11.3117

Larussa, T., Imeneo, M. and Luzza, F. 2017. Potential role of nutraceutical compounds in inflammatory bowel disease. World J. Gastroenterol. 23(14):2483–2492. 10.3748/wjg.v23.i14.2483

Lenoir, L., Rossary, A., Joubert-Zakeyh, J., Vergnaud-Gauduchon, J., Farges, M-C., Fraisse, D., Texier, O., Lamaison, J.L., Vasson, M.P. and Felgines, C. 2011. Lemon verbena infusion consumption attenuates oxidative stress in dextran sulfate sodium-induced colitis in the rat. Dig Dis Sci. 56(12):3534–3545. 10.1007/s10620-011-1784-x

Lewellyn, S.R., Britton, G.J., Contijoch, E.J., Mortha, A.J.F., Colombel, J.F.A., Grinspan, A., Clemente, J.C., Merad, M. and Faith, J.J. 2017. Deciphering the combinatorial influence of diet and the microbiota on experimental colitis. BioRxiv. 117929. Epub ahead of print. 10.1101/117929

Lin, SC. and Cheifetz, A.S. 2018. The use of complementary and alternative medicine in patients with inflammatory bowel disease. Gastroenterol Hepatol. 14(7):415–425. PMid: 30166957.

Liu, Y., Wang, X., Hou, Y., Yin, Y., Qiu, Y., Wu, G. and Hu, C.A.A. 2017. Roles of amino acids in preventing and treating intestinal diseases: recent studies with pig models. Amino Acids. 49(8):1277–1291. 10.1007/s00726-017-2450-1

Lowry, O.H., Rose Rough, NJ., Farr, AL. and Randall, RJ. 1951. Protein measurement with the folin phenol reagent. J Biol Chem. 193(1):265–275. 10.1016/S0021-9258(19)52451-6

Makrane, H., Aziz, M., Mekhfi, H., Ziyyat, A., Legssyer, A. and Melhaoui, A. 2018. Origanum majorana L. extract exhibit positive cooperative effects on the main mechanisms involved in acute infectious diarrhoea. J Ethnopharmacol. 239:111503. 10.1016/j.jep.2018.09.005

Maloy, K.J. and Powrie, F. 2011. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 474(7351):298–306. 10.1038/nature10208

Malle, E., Furtmüller, P.G., Sattler, W. and Obinger, C. 2007. Myeloperoxidase: a target for new drug development? Br J Pharmacol. 152(6):838–854. 10.1038/Fsj.bjp.0707358

Mandalari, G., Bisignano, C., Genovese, T., Mazzon, E., Wickham, M.S. and Paterniti, I. 2011. Natural almond skin reduced oxidative stress and inflammation in an experimental model of inflammatory bowel disease. Int Immunopharmacol. 11(8):915–24. 10.1016/j.intimp.2011.02.003

Marklund, S.L. and Marklund, G. 1974. Involvement of superoxide anion radical in the autooxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 47(3):469–474. 10.1111/j.1432-1033.1974.tb03714.x

Mazur-Bialy, A.I., Bilski, J., Wojcik, D., Brzozowski, B., Surmiak, M., Hubalewska Mazgaj, M., Chmura, A., Magierowski, M., Magierowska, K. and Mach, T. 2017. Beneficial effect of voluntary exercise on experimental colitis in mice fed a high-fat diet: the role of irisin, adiponectin and proinflammatory biomarkers. Nutrients. 9(4):410. 10.3390/nu9040410

Mekkioui, A. and Djerdjouri, B. 2012. N-acetylcysteine improves redox status, mitochondrial dysfunction, mucin-depleted crypts and epithelial hyperplasia in dextran sulfate sodium-induced oxidative colitis in mice. Eur J Pharmacol. 691(1–3):209–217. 10.1016/j.ejphar.2012.06.014

Mijan, A.L. and Lim, B.O. 2018. Diets. Functional foods and nutraceuticals as alternative therapies for inflammatory bowel disease: present status and future trends. World J Gastroenterol. 24(25):2673–2685. 10.3748/Fwjg.v24.i25.2673

Młodzik-Danielewicz, N. and Tyrakowski, T. 2005. Effects of amiloride and bumetanide on hyperpolarization after movement across the distal colon epithelium. Pharmacol Rep. 57(4):489–497. PMid: 16129916.

Mossa, A.T., Refaie, A.A., Ramadan, A. and Bouajila, J. 2013. Amelioration of prallethrin-induced oxidative stress and hepatotoxicity in rat by the administration of Origanum majorana essential oil. Biomed Res Int. 2013:859085. 10.1155/2013/859085

Mueller, K., Blum, N.M. and Mueller, A.S. 2013. Examination of the anti-inflammatory, antioxidant, and xenobiotic-inducing potential of broccoli extract and various essential oils during a Mild DSS-induced colitis in rats. ISRN Gastroenterol. 2013:710856. 10.1155/2013/710856

Nishiyama, Y., Kataoka, T., Yamato, K., Taguchi, T. and Yamaoka, K. 2012. Suppression of dextran sulfate sodium-induced colitis in mice by radon inhalation. Mediators Inflamm. 2012:239617. 10.1155/2012/239617

Okayasu, I., Hatakeyama, S., Yamada, M., Ohkusa, T., Inagaki, Y. and Nakaya, R. 1990. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 98(3):694–702. 10.1016/0016-5085(90)90290-h

Oz, H.S., Chen, T.S., McClain, C.J. and de Villiers, W.J.S. 2005. Antioxidants as novel therapy in a murine model of colitis. J Nutr Biochem. 16(5):297–304. 10.1016/j.jnutbio.2004.09.007

Pandurangan, A.K., Mohebali, N., Norhaizan, M.E. and Looi, C.Y. 2015. Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice. Drug Des Devel Ther. 9:3923–3934. 10.2147/FDDDT.S86345

Paterson, J.R., Srivastava, R., Baxter, G.J., Graham, A.B. and Lawrence, J.R. 2006. Salicylic acid content of spices and its implications. J Agric Food Chem. 54(8):2891–2896. 10.1021/jf058158w

Perse, M. and Cerar, A. 2012. Dextran sodium sulphate colitis mouse model: traps and tricks. Biomed Biotechnol. 2012:718617. 10.1155/2012/718617

Ramadan, G., El-Beih, N.M., Arafa, NM. and Zahra, M.M. 2013. Preventive effects of Egyptian sweet marjoram (Origanum majorana L.) leaves on hematological changes and cardiotoxicity in isoproterenol-treated albino rats. Cardiovasc Toxicol. 13(2):100–109. 10.1007/s12012-012-9189-4

Rodrigues, M.R.A., Caram̃ao, E.B., Arce, L., R´ıos, A. and Valc´arcel, M. 2002. Determination of monoterpene hydrocarbons and alcohols in Majorana shortness Moench by micellar electro kinetic capillary chromatographic. J Agric Food Chem. 50(15):4215–4220. 10.1021/jf011667n

Salih, A.M., Smith, D.M., Price, J.F. and Dawson, L.E. 1987. Modifid extraction 2 thiobarbituric acid method for measuring lipid oxidation in pountry. Poultry Sci. 66(9):1483–1488. 10.3382/ps.0661483

Sedlak, J. and Lindsay, R.H. 1968. Estimation of total, protein-bound, and non-protein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 25(1):192–205. 10.1016/0003-2697(68)90092-4

Stillie, R. and Stadnyk, A.W. 2009. Role of TNF receptors, TNFR1 and TNFR2 in dextran sodium sulfate-induced colitis. Inflamm Bowel Dis. 15(10):1515–1525. 10.1002/ibd.20951

Su, L., Nalle, S.C., Shen, L., Turner, E.S., Singh, G., Breskin, L.A., Khramtsova, E.A., Khramtsova, G., Tsai, P.Y., Fu, Y.X.C., Abraham, C.J.R. and Turner, J.R. 2013. TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis. Gastroenterology. 145(2):407–415. 10.1053/j.gastro.2013.04.011

Tahan, G., Aytac, E., Aytekin, H., Gunduz, F., Dogusoy, G., Aydin, S., Tahan, V. and Uzun, H. 2011. Vitamin E has a dual effect of anti-inflammatory and antioxidant activities in acetic acid-induced ulcerative colitis in rats. Can J Surg. 54(5):333–338. 10.1503/cjs.013610

Trouillas, P., Calliste, C.A., Allais, DP., Simon, A., Ma, A., Delage, C. and Duroux, J.L. 2003. Antioxidant, anti-inflammatory and antioxidant antiproliferative properties of sixteen water plant extracts used in the Limousin countryside as herbal teas. Food Chem. 80(3):399–407. 10.1016/S0308-8146(02)00282-0

Uko, V., Thangada, S. and Radhakrishnan, K. 2012. Liver disorders in inflammatory bowel disease. Gastroenterol Res Pract. 2012:642923. 10.1155/2012/642923

Valatas, V., Vakas, M. and Kolios, G. 2013. The value of experimental models of colitis in predicting efficacy of biological therapies for inflammatory bowel diseases. Am. J. Physiol. Gastrointest. Liver Physiol. 305(11):763–785. 10.1152/ajpgi.00004.2013

Wan, P., Chen, H., Guo, Y. and Bai, A.P. 2014. Advances in treatment of ulcerative colitis with herbs: from bench to bedside. World J Gastroenterol. 20(39):14099–14104. 10.3748/wjg.v20.i39.14099

Wang, Z., Adachi, S., Kong, L., Watanabe, D., Nakanishi, Y., Ohteki, T., Hoshi, N. and Kodama, Y. 2019. Role of eosinophils in a murine model of inflammatory bowel disease. Biochem Biophys Res Commun. 511(1):99–104. 10.1016/j.bbrc.2019.02.056

Wardman, P. 2007. Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: progress, pitfalls, and prospects. Free Radic Biomed. 43(7):995–1022. 10.1016/j.freeradbiomed.2007.06.026

Xing, J., You, C., Dong, K., Sun, J., You, H. and Dong, Y. 2013. Ameliorative effects of 3,4-oxo isopropylideneshikimic acid on experimental colitis and their mechanisms in rats. Int Immunopharmacol. 15(3):524–31. 10.1016/j.intimp.2013.02.008

Xu, L., Yang, Z.L., Li, P. and Zhou, Y.Q. 2009. Modulating effect of hesperidin on experimental murine colitis induced by dextran sulfate sodium. Phytomedicine. 16(10):989–995. 10.1016/j.phymed.2009.02.021

Yan, H., Wang, H., Zhang, X., Li, X. and Y.J. 2015. Ascorbic acid ameliorates oxidative stress and inflammation in dextran sulfate sodium induced ulcerative colitis in mice. Int J Clin Exp Med. 8(11):20245–20253.

Yang, B.L., Chen, Y.G. and Gu, Y.F. 2015. Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn’s disease. World J Gastroenterol. 21(8):2475–2482. 10.3748/Fwjg.v21.i8.2475

Zhu, H. and Li, Y.R. 2012. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med (Maywood). 237(5):474–480. 10.1258/ebm.2011.011358