Ameliorative effect of galantamine on acetic acid-induced colitis in rats

Niloofar-Sadat Mahdavi, Ardeshir Talebi, Mohsen Minaiyan


Galantamine (GAL) is a drug for treating Alzheimer’s disease which has reasonable and no significant side effects. Studies have shown that GAL possesses antioxidant, anti-inflammatory, and cholinomimetic effects that might be beneficial for inflammatory bowel disease. Therefore, this study was aimed to investigate the anti-inflammatory effect of GAL on acetic acid-induced colitis in rats. GAL at 0.25, 1.25, 2.5 mg/kg/day was administrated orally (p.o.) to different groups of male Wistar rats 2 h before induction of ulcer with acetic acid 3% and continued for 5 consecutive days. Dicyclomine (DIC) was similarly used alone (5 mg/kg/day, p.o.) or together with GAL at doses already mentioned to delineate the impact of muscarinic pathway in probable beneficial effects of GAL on colitis. Control and reference groups received distilled water (5 mL/kg, p.o.), prednisolone (4 mg/kg/day, p.o.), or mesalazine (100 mg/kg/day, p.o.) respectively. At day 6, tissue injuries were assessed for macroscopic, histopathologic, and biochemical indices of myeloperoxidase and MPO activity. Results showed that GAL at 3 applied doses, alone or in combination with DIC diminished ulcer index, total colitis index, and MPO activity as important biomarkers of colitis. DIC alone was not effective on most parameters and its concurrent administration with GAL couldn’t reverse its antiulcerative effects. Prednisolone and mesalazine were both effective in this relation. The current research indicated that GAL had anti-inflammatory and antiulcerative activities independent of its muscarinic effects. Thus the antioxidant and anti-inflammatory effects may account for its anti-inflammatory and anti-ulcerative properties. Nevertheless, further detailed studies are warranted for exact elucidation of GAL mechanism on inflammation and colitis.


Anticholinergic; Anti-inflammatory; Dicyclomine; Galantamine; Ulcerative colitis; Rats.

Full Text:



Hanauer SB. Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis. 2006;12(Suppl 1):3-9.

Rahimi R, Shams-Ardekani MR, Abdollahi M. A review of the efficacy of traditional Iranian medicine for inflammatory bowel disease. World J Gastroenterol. 2010;16(36):4504-4514.

Katzung BG. Basic and clinical pharmacology.14th ed. New York: Lange Medical Publications; 2018. pp. 1106-1111.

Rawla P, Sunkara T, Raj JP. Role of biologics and biosimilars in inflammatory bowel disease: current trends and future perspectives. J Inflamm Res. 2018;11:215-226.

Arnott I, Rogler G, Halfvarson J. The management of inflammatory bowel disease in elderly: current evidence and future perspectives. Inflamm Intest Dis. 2018;2(4):189-199.

Tafti LD, Shariatpanahi SM, Damghani MM, Javadi B. Traditional Persian topical medications for gastrointestinal diseases. Iran J Basic Med Sci. 2017;20(3):222-241.

Minaiyan M, Ghannadi A, Mahzouni P, Jaffari-Shirazi E. Comparative study of Berberis vulgaris fruit extract and berberine chloride effects on acetic acid-induced colitis in rats. Iran J Pharm Res. 2011;10(1):97-104.

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(4):322-329.

Minaiyan M, Ghannadi A, Etemad M, Mahzouni P. A study of the effects of Cydonia oblonga Miller (Quince) on TNBS-induced ulcerative colitis in rats. Res Pharm Sci. 2012;7:103-110.

Minaiyan M, Ghannadi A, Asadi M, Etemad M, Mahzouni P. Anti-inflammatory effect of Prunus armeniaca L. (Apricot) extracts ameliorates TNBS-induced ulcerative colitis in rats. Res Pharm Sci. 2014;9(4):225-231.

Wu TY, Chen CP, Jinn TR. Traditional Chinese medicines and Alzheimer’s disease. Taiwan J Obstet Gynecol. 2011;50(2):131-135.

Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomized trial. Lancet. 2002;359(9314):1283-1290.

Ago Y, Koda K, Takuma K, Matsuda T. Pharmacological aspects of the acetylcholinesterase inhibitor galantamine. J Pharmacol Sci. 2011;116(1):6-17.

Pavlov VA, Parrish WR, Rosas-ballina M, Ochani M, Puerta M, Ochani K, et al. Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Brain Behav Immun. 2009;23(1):41-45.

Dajas-Bailador FA, Heimala K, Wonnacott S. The allosteric potentiation of nicotinic acetylcholine receptors by galantamine is transduced into cellular responses in neurons: Ca2+ signals and neurotransmitter release. Mol Pharmacol. 2003;64(5):1217-1226.

Tsvetkova D, Obreshkova D, Zheleva-dimitrova D, Saso L. Antioxidant activity of galantamine and some of its derivatives. Curr Med Chem. 2013;20(36):4595-4608.

Sammi SR, Rawat JK, Raghav N, Kumar A, Roy S, Singh M, et al. Galantamine attenuates N,N-dimethyl hydrazine induced neoplastic colon damage by inhibiting acetylcholinesterase and bimodal regulation of nicotinic cholinergic neurotransmission. Eur J Pharmacol. 2018;818: 174-183.

Ritter JM, Flower R, Henderson G, Kong-Loke Y, MacEwan D, Rang HP. Rang & Dales Pharmacology. 9th ed. Edinburg: Elsevier; 2020. pp. 521-522.

Mimica N, Presečki P. Side effects of approved antidementives. Psychiatr Danub. 2009;21(1):108-113.

Minaiyan M, Asghari G, Taheri D, Saeidi M, Nasr-Esfahani S. Anti-inflammatory effect of Moringa oleifera Lam. seeds on acetic acid-induced acute colitis in rats. Avicenna J Phytomed. 2014;4(2):127-136.

Rashidian A, Roohi P, Mehrzadi S, Ghannadi AR, Minaiyan M. Protective effect of Ocimum basilicum essential oil against acetic acid-induced colitis in rats. J Evid Based Complementary Altern Med. 2016;21(4):NP36-NP42.

Minaiyan M, Ghassemi-Dehkordi N,Mahzouni P, Ansari-Roknabady M. Effect of Matricaria aurea (Loefl.) Shultz-Bip. hydroalcoholic extract on acetic acid-induced acute colitis in rats. Iranian J Basic Med Sci. 2011;14(1):67-74.

Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993;69(2):238-249.

Varshosaz J, Emami J, Ahmadi F, Tavakoli N, Minaiyan M, Fassihi A, et al. Preparation of budesonide-dextran conjugates using glutarate spacer as a colon-targeted drug delivery system: in vitro/in vivo evaluation in induced ulcerative colitis. J Drug Target. 2011;19(2):140-153.

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.

Bennett PN, Brown MJ, Sharma P. Clinical pharmacology, 11th ed. Edinburgh: Elsevier, Churchill Livingstone; 2013. pp. 344-345.

Wazea SA, Wadie W, Bahgat AK, El-Abhar HS. Galantamine anti-colitic effect: role of alpha-7 nicotinic acetylcholine receptor in modulating Jak/STAT3, NF-κB/HMGB1/RAGE and p-AKT/Bcl-2 pathways. Sci Rep. 2018;8(1):5110-5119.

Motavallian A, Minaiyan M, Rabbani M, Mahzouni P, Andalib S, Abed A, et al. Does cisapride, as a 5HT(4) receptor agonist, aggravate the severity of TNBS-induced colitis in rat? Gastroenterol Res Pract. 2012;2012. Article ID 362536, 8 pages.

Gowayed MA, Refaat R, Ahmed WM, El-Abhar HS. Effect of galantamine on adjuvant-induced arthritis in rats. Eur J Pharmacol. 2015;764:547-553.

Liu H, Lai M, Zhou X, Zhu H, Liu Y, Sun A, et al. Galantamine attenuates the heroin seeking behaviors induced by cues after prolonged withdrawal in rats. Neuropharmacology. 2012;62(8):2515-2521.

Park YS, Kim SH, Kim SY, Kim YH, Lee MH, Yang SC, et al. Quantification of galantamine in human plasma by validated liquid chromatography-tandem mass spectrometry using glimepride as an internal standard: application to bioavailability studies in 32 healthy Korean subjects. J Chromatogr Sci. 2012;50(9):803-809.

Melo JB, Sousa C, Garção P, Oliveira CR, Agostinho P. Galantamine protects against oxidative stress induced by amyloid-beta peptide in cortical neurons. Eur J Neurosci. 2009;29(3):455-464.

Li G, Zhou CL, Zhou QS, Zou HD. Galantamine protects against lipopolysaccharide-induced acute lung injury in rats. Braz J Med Biol Res. 2016;49(2):e5008-e5014.

Kolgazi M, Uslu U, Yuksel M, Velioglu-Ogunc A, Ercan F, Alican I. The role of cholinergic anti-inflammatory pathway in acetic acid-induced colonic inflammation in the rat. Chem Biol Interact. 2013;205(1):72-80.

Alves de Almeida AC, de-Faria FM, Dunder RJ, Manzo LP, Souza-Brito AR, Luiz-Ferreira A. Recent trends in pharmacological activity of alkaloids in animal colitis: potential use for inflammatory bowel disease. Evid Based Complement Alternat Med. 2017;2017. Article ID 8528210, 24 pages.

Shifrin H, Mouhadeb O, Gluck N, Varol C, Weinstock M. Cholinergic anti-inflammatory pathway does not contribute to prevention of ulcerative colitis by novel indoline carbamates. J Neuroimmune Pharmacol. 2017;12(3):484-491.

Murray K, Reardon C. The cholinergic anti-inflammatory pathway revisited. Neurogastroenterol Motil. 2018;30(3): 12 pages. DOI: 10.1111/nmo.13288.


  • There are currently no refbacks.

Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.