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Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

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ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

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Research Article

Cinnamic Acid Ameliorates Acetic Acid-induced Inflammatory Response through Inhibition of TLR-4 in Colitis Rat Model

Author(s): Zahra Rezaei, Saeideh Momtaz*, Pardis Gharazi, Mahban Rahimifard, Maryam Baeeri, Ali Reza Abdollahi, Mohammad Abdollahi, Amirhossein Niknejad, Danial Khayatan, Mohammad Hosein Farzaei and Amir Hossein Abdolghaffari*

Volume 23, Issue 1, 2024

Published on: 29 January, 2024

Page: [21 - 30] Pages: 10

DOI: 10.2174/0118715230278980231212103709

Price: $65

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Abstract

Background: Cinnamic acid, an active compound in cinnamon spp., has anti-inflammatory and antioxidant characteristics and is favorable in managing inflammatory bowel diseases. Objectives: Evaluate cinnamic acid's effects on colitis in rats.

Methods: To induce colitis in experimental rats, excluding the sham group, a 4% intrarectal solution of acetic acid was administered. The rats were then given oral doses of cinnamic acid at 30, 45, and 90 mg/kg for two days. The animals were assessed for macroscopic and microscopic changes, and the levels of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured using Eliza kits. Additionally, real-time PCR was performed to examine the gene level of toll-like receptor 4 (TLR-4) in the colon.

Results: Effective reduction of inflammation in acetic acid-induced colitis was achieved through Cinnamic acid administration at doses of 45 and 90 mg/kg. The decrease was achieved by inhibiting the activities of TNF-α, IL-6, and MPO while downregulating the expression of TLR-4. It is important to note that macroscopic and microscopic evaluations were significant in determining the effectiveness of cinnamic acid in reducing inflammation.

Conclusion: Downregulation of inflammatory cytokines and TLR-4 expression may contribute to cinnamic acid's anti-inflammatory effect.

Keywords: Cinnamic acid, Inflammatory bowel disease (IBD), Interleukin-6 (IL-6), Myeloperoxidase (MPO), Toll-like receptor- 4 (TLR-4), Tumor necrosis factor-alpha (TNF-α).

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[1]
Vermeire, S.; Van Assche, G.; Rutgeerts, P. Classification of inflammatory bowel disease. Curr. Opin. Gastroenterol., 2012, 28(4), 321-326.
[http://dx.doi.org/10.1097/MOG.0b013e328354be1e] [PMID: 22647554]
[2]
Zhao, M.; Feng, R.; Ben-Horin, S.; Zhuang, X.; Tian, Z.; Li, X.; Ma, R.; Mao, R.; Qiu, Y.; Chen, M. Systematic review with meta-analysis: Environmental and dietary differences of inflammatory bowel disease in Eastern and Western populations. Aliment. Pharmacol. Ther., 2022, 55(3), 266-276.
[http://dx.doi.org/10.1111/apt.16703] [PMID: 34820868]
[3]
Neurath, M.F. Cytokines in inflammatory bowel disease. Nat. Rev. Immunol., 2014, 14(5), 329-342.
[http://dx.doi.org/10.1038/nri3661] [PMID: 24751956]
[4]
Li, D.; Wu, M. Pattern recognition receptors in health and diseases. Signal Transduct. Target Ther., 2021, 6(1), 291.
[http://dx.doi.org/10.1038/s41392-021-00687-0] [PMID: 34344870]
[5]
Curciarello, R.; Canziani, K.E.; Docena, G.H.; Muglia, C.I. Contribution of non-immune cells to activation and modulation of the intestinal inflammation. Front. Immunol., 2019, 10, 647.
[http://dx.doi.org/10.3389/fimmu.2019.00647] [PMID: 31024529]
[6]
Zhang, Y.; Zha, Z.; Shen, W.; Li, D.; Kang, N.; Chen, Z.; Liu, Y.; Xu, G.; Xu, Q. Anemoside B4 ameliorates TNBS-induced colitis through S100A9/MAPK/NF-κB signaling pathway. Chin. Med., 2021, 16(1), 11.
[http://dx.doi.org/10.1186/s13020-020-00410-1] [PMID: 33461587]
[7]
Cario, E. Toll-like receptors in inflammatory bowel diseases: A decade later. Inflamm. Bowel Dis., 2010, 16(9), 1583-1597.
[http://dx.doi.org/10.1002/ibd.21282] [PMID: 20803699]
[8]
Davies, M.J. Myeloperoxidase-derived oxidation: Mechanisms of biological damage and its prevention. J. Clin. Biochem. Nutr., 2010, 48(1), 8-19.
[http://dx.doi.org/10.3164/jcbn.11-006FR] [PMID: 21297906]
[9]
Kothari, N.; Keshari, R.S.; Bogra, J.; Kohli, M.; Abbas, H.; Malik, A.; Dikshit, M.; Barthwal, M.K. Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis. J. Crit. Care, 2011, 26(4), 435.e1-435.e7.
[http://dx.doi.org/10.1016/j.jcrc.2010.09.001] [PMID: 21036525]
[10]
Ndrepepa, G. Myeloperoxidase – A bridge linking inflammation and oxidative stress with cardiovascular disease. Clin. Chim. Acta, 2019, 493, 36-51.
[http://dx.doi.org/10.1016/j.cca.2019.02.022] [PMID: 30797769]
[11]
Khan, A.; Alsahli, M.; Rahmani, A. Myeloperoxidase as an active disease biomarker: Recent biochemical and pathological perspectives. Med. Sci., 2018, 6(2), 33.
[http://dx.doi.org/10.3390/medsci6020033] [PMID: 29669993]
[12]
Ruwizhi, N.; Aderibigbe, B.A. Cinnamic acid derivatives and their biological efficacy. Int. J. Mol. Sci., 2020, 21(16), 5712.
[http://dx.doi.org/10.3390/ijms21165712] [PMID: 32784935]
[13]
Minaiyan, M.; Karimi, F.; Ghannadi, A. Anti-inflammatory effect of Pistacia atlantica subsp. kurdica volatile oil and gum on acetic acid-induced acute colitis in rat. Research Journal of Pharmacognosy, 2015, 2(2), 1-12.
[14]
Pontiki, E.; Hadjipavlou-Litina, D. Multi-target cinnamic acids for oxidative stress and inflammation: design, synthesis, biological evaluation and modeling studies. Molecules, 2018, 24(1), 12.
[http://dx.doi.org/10.3390/molecules24010012] [PMID: 30577525]
[15]
Shimizu, Y.; Suzuki, T. Brazilian propolis extract reduces intestinal barrier defects and inflammation in a colitic mouse model. Nutr. Res., 2019, 69, 30-41.
[http://dx.doi.org/10.1016/j.nutres.2019.07.003] [PMID: 31470289]
[16]
Fakhraei, N.; Abdolghaffari, A.H.; Delfan, B.; Abbasi, A.; Rahimi, N.; Khansari, A.; Rahimian, R.; Dehpour, A.R. Protective effect of hydroalcoholic olive leaf extract on experimental model of colitis in rat: Involvement of nitrergic and opioidergic systems. Phytother. Res., 2014, 28(9), 1367-1373.
[http://dx.doi.org/10.1002/ptr.5139] [PMID: 24590915]
[17]
Song, F.; Li, H.; Sun, J.; Wang, S. Protective effects of cinnamic acid and cinnamic aldehyde on isoproterenol-induced acute myocardial ischemia in rats. J. Ethnopharmacol., 2013, 150(1), 125-130.
[http://dx.doi.org/10.1016/j.jep.2013.08.019] [PMID: 24001892]
[18]
Antonioli, L.; Fornai, M.; Colucci, R.; Ghisu, N.; Da Settimo, F.; Natale, G.; Kastsiuchenka, O.; Duranti, E.; Virdis, A.; Vassalle, C.; La Motta, C.; Mugnaini, L.; Breschi, M.C.; Blandizzi, C.; Del Taca, M. Inhibition of adenosine deaminase attenuates inflammation in experimental colitis. J. Pharmacol. Exp. Ther., 2007, 322(2), 435-442.
[http://dx.doi.org/10.1124/jpet.107.122762] [PMID: 17488880]
[19]
Morris, G.P.; Beck, P.L.; Herridge, M.S.; Depew, W.T.; Szewczuk, M.R.; Wallace, J.L. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology, 1989, 96(3), 795-803.
[http://dx.doi.org/10.1016/0016-5085(89)90904-9] [PMID: 2914642]
[20]
Murthy, S.N.S.; Cooper, H.S.; Shim, H.; Shah, R.S.; Ibrahim, S.A.; Sedergran, D.J. Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Dig. Dis. Sci., 1993, 38(9), 1722-1734.
[http://dx.doi.org/10.1007/BF01303184] [PMID: 8359087]
[21]
El-Far, A.H.; Lebda, M.A.; Noreldin, A.E.; Atta, M.S.; Elewa, Y.H.A.; Elfeky, M.; Mousa, S.A. Quercetin attenuates pancreatic and renal d-galactose-induced aging-related oxidative alterations in rats. Int. J. Mol. Sci., 2020, 21(12), 4348.
[http://dx.doi.org/10.3390/ijms21124348] [PMID: 32570962]
[22]
Teng, Y.; Kang, H.; Chu, Y. Identification of an exosomal long noncoding rna sox2-ot in plasma as a promising biomarker for lung squamous cell carcinoma. Genet. Test. Mol. Biomarkers, 2019, 23(4), 235-240.
[http://dx.doi.org/10.1089/gtmb.2018.0103] [PMID: 30986097]
[23]
Kucharzik, T.; Maaser, C.; Lügering, A.; Kagnoff, M.; Mayer, L.; Targan, S.; Domschke, W. Recent understanding of IBD pathogenesis: Implications for future therapies. Inflamm. Bowel Dis., 2006, 12(11), 1068-1083.
[http://dx.doi.org/10.1097/01.mib.0000235827.21778.d5] [PMID: 17075348]
[24]
Brown, S.J.; Mayer, L. The immune response in inflammatory bowel disease. Am. J. Gastroenterol., 2007, 102(9), 2058-2069.
[http://dx.doi.org/10.1111/j.1572-0241.2007.01343.x] [PMID: 17561966]
[25]
Lashgari, N.A.; Roudsari, N.M.; Shayan, M.; Niazi Shahraki, F. hosseini, Y.; Momtaz, S.; Abdolghaffari, A.H. IDO/Kynurenine; novel insight for treatment of inflammatory diseases. Cytokine, 2023, 166156206
[http://dx.doi.org/10.1016/j.cyto.2023.156206] [PMID: 37120946]
[26]
Elsässer-Beile, U.; von Kleist, S.; Gerlach, S.; Gallati, H.; Mönting, J.S. Cytokine production in whole blood cell cultures of patients with crohn’s disease and ulcerative colitis. J. Clin. Lab. Anal., 1994, 8(6), 447-451.
[http://dx.doi.org/10.1002/jcla.1860080618] [PMID: 7869186]
[27]
Momtaz, S.; Navabakhsh, M.; Bakouee, N.; Dehnamaki, M.; Rahimifard, M.; Baeeri, M.; Abdollahi, A.; Abdollahi, M.; Farzaei, M.H.; Abdolghaffari, A.H. Cinnamaldehyde target TLR-4 and inflammatory mediators in acetic-acid induced ulcerative colitis model. Biologia, 2021, 76(6), 1817-1827.
[http://dx.doi.org/10.1007/s11756-021-00725-w]
[28]
Lu, Y.; Li, X.; Liu, S.; Zhang, Y.; Zhang, D. Toll-like receptors and inflammatory bowel disease. Front. Immunol., 2018, 9, 72.
[http://dx.doi.org/10.3389/fimmu.2018.00072] [PMID: 29441063]
[29]
Scaldaferri, F.; Fiocchi, C. Inflammatory bowel disease: Progress and current concepts of etiopathogenesis. J. Dig. Dis., 2007, 8(4), 171-178.
[http://dx.doi.org/10.1111/j.1751-2980.2007.00310.x] [PMID: 17970872]
[30]
Kainulainen, V.; Tang, Y.; Spillmann, T.; Kilpinen, S.; Reunanen, J.; Saris, P.; Satokari, R. The canine isolate Lactobacillus acidophilus LAB20 adheres to intestinal epithelium and attenuates LPS-induced IL-8 secretion of enterocytes in vitro. BMC Microbiol., 2015, 15(1), 4.
[http://dx.doi.org/10.1186/s12866-014-0337-9] [PMID: 25591990]
[31]
Lee, J.H.; Lee, B.; Lee, H.S.; Bae, E.A.; Lee, H.; Ahn, Y.T.; Lim, K.S.; Huh, C.S.; Kim, D.H. Lactobacillus suntoryeus inhibits pro-inflammatory cytokine expression and TLR-4-linked NF-κB activation in experimental colitis. Int. J. Colorectal Dis., 2009, 24(2), 231-237.
[http://dx.doi.org/10.1007/s00384-008-0618-6] [PMID: 19050899]
[32]
Li, Z.; Zhang, D.K.; Yi, W.Q.; Ouyang, Q.; Chen, Y.Q.; Gan, H.T. NF-kappaB p65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with ulcerative colitis. Arch. Med. Res., 2008, 39(8), 729-734.
[http://dx.doi.org/10.1016/j.arcmed.2008.08.001] [PMID: 18996285]
[33]
Xu, F.; Wang, F.; Wen, T.; Sang, W.; He, X.; Li, L.; Zeng, N. Protective effect of cinnamic acid in endotoxin-poisoned mice. Phytother. Res., 2017, 31(12), 1946-1953.
[http://dx.doi.org/10.1002/ptr.5944] [PMID: 29024091]
[34]
Cordes, F.; Foell, D.; Ding, J.N.; Varga, G.; Bettenworth, D. Differential regulation of JAK/STAT-signaling in patients with ulcerative colitis and Crohn’s disease. World J. Gastroenterol., 2020, 26(28), 4055-4075.
[http://dx.doi.org/10.3748/wjg.v26.i28.4055] [PMID: 32821070]
[35]
Kuppusamy, P.; Soundharrajan, I.; Kim, D.H.; Hwang, I.; Choi, K.C. 4-hydroxy-3-methoxy cinnamic acid accelerate myoblasts differentiation on C2C12 mouse skeletal muscle cells via AKT and ERK 1/2 activation. Phytomedicine, 2019, 60152873
[http://dx.doi.org/10.1016/j.phymed.2019.152873] [PMID: 30879871]

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