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Current Bioactive Compounds


ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

Intestinal Anti-inflammatory Effects of Linum usitatissimum Alkaloid on Experimental Ulcerative Colitis in BALB/c Mice

Author(s): Noureddine Bribi*, Mohamed Sofiane Merakeb and Hania Boudaoud-Ouahmed

Volume 19, Issue 8, 2023

Published on: 15 May, 2023

Article ID: e170423215930 Pages: 6

DOI: 10.2174/1573407219666230417112912

Price: $65


Introduction: There is growing interest in alternative therapies for managing inflammatory bowel disorders (IBD) that offer efficacy and a suitable safety profile. The present study aimed to evaluate the intestinal anti-inflammatory effect of the alkaloid extract of Linum usitatissimum (ALU) on the acetic acid (AA) experimental model of colitis.

Methods: For in vivo experiments, an 8-day 5% acetic acid administration protocol was used in BALB/c mice to induce colitis. The intestinal anti-inflammatory effect of oral ALU (12.5, 25, and 50mg/kg) was evaluated after 8 days. Colon damage was evaluated macroscopically (colon weight/ colon length), and the histological alterations were also assessed.

Results: ALU treatment significantly reduced signs of intestinal inflammation compared to the Acetic acid control mice, confirmed by histological examination.

Conclusion: These results suggest that the total alkaloid extract from Linum usitatissimum seeds has potent intestinal anti-inflammatory properties and may be a promising treatment for ulcerative colitis.

Keywords: Anti-inflammatory, ulcerative colitis, Linum usitatissimum, alkaloid, acetic acid, IBDs.

Graphical Abstract
Hilfiker-Kleiner, D.; Azibani, F. Etiology and pathophysiology. Peripartum Cardiomyopathy., 2021, 347(6), 1-11.
Impellizzeri, D.; Bruschetta, G.; Di Paola, R.; Ahmad, A.; Campolo, M.; Cuzzocrea, S.; Esposito, E.; Navarra, M. The anti-inflammatory and antioxidant effects of bergamot juice extract (BJe) in an experimental model of inflammatory bowel disease. Clin. Nutr., 2015, 34(6), 1146-1154.
[] [PMID: 25491246]
Engel, M.A.; Neurath, M.F. New pathophysiological insights and modern treatment of IBD. J. Gastroenterol., 2010, 45(6), 571-583.
[] [PMID: 20213337]
Baumgart, D.C.; Sandborn, W.J. Inflammatory bowel disease: Clinical aspects and established and evolving therapies. Lancet, 2007, 369(9573), 1641-1657.
[] [PMID: 17499606]
Chen, Y.S.; Lian, Y.Z.; Chen, W.C.; Chang, C.C.; Tinkov, A.A.; Skalny, A.V.; Chao, J.C.J. Lycium barbarum polysaccharides and capsaicin inhibit oxidative stress, inflammatory responses, and pain signaling in rats with dextran sulfate sodium-induced colitis. Int. J. Mol. Sci., 2022, 23(5), 2423.
[] [PMID: 35269566]
Mehta, S.J.; Silver, A.R.; Lindsay, J.O. Review article: Strategies for the management of chronic unremitting ulcerative colitis. Aliment. Pharmacol. Ther., 2013, 38(2), 77-97.
[] [PMID: 23718288]
Adamshafi, S.; Veera, V. Synthesis of novel nsaids linked to triazolyl-oxadiazole heterocyclic compounds as more comprehensive antimicrobial agents: A computational molecular docking. Curr. Bioact. Compd., 2022, 18(2), 39-52.
Faubion, W.A., Jr; Loftus, E.V., Jr; Harmsen, W.S.; Zinsmeister, A.R.; Sandborn, W.J. The natural history of corticosteroid therapy for inflammatory bowel disease: A population-based study. Gastroenterology, 2001, 121(2), 255-260.
[] [PMID: 11487534]
Mohamed, H. AL-Ghareeb, M.; Abd-Allah, R. Pharmacological evaluation of novel 1,2,4-triazine derivatives containing thiazole ring against hepatocellular carcinoma. Curr. Bioact. Compd., 2022, 18(2), 12-25.
Bastaki, S.M.A.; Adeghate, E.; Amir, N.; Ojha, S.; Oz, M. Menthol inhibits oxidative stress and inflammation in acetic acid-induced colitis in rat colonic mucosa. Am. J. Transl. Res., 2018, 10(12), 4210-4222.
[PMID: 30662664]
Bribi, N. Anti-nociceptive and anti-inflammatory effects of paeonia mascula extract. J. Pharm. Pharmacogn. Res., 2018, 6(2), 81-88.
Zhang, S.Z.; Zhao, X.H.; Zhang, D.C. Cellular and molecular immunopathogenesis of ulcerative colitis. Cell. Mol. Immunol., 2006, 3(1), 35-40.
[PMID: 16549047]
Singh, B.; Sahu, P.; Sharma, R. Phytochemical profiling, anti-inflammatory, antioxidant and antimicrobial effects of seven Indian Morinda species. Curr. Bioact. Compd., 2022, 18(2), 26-38.
Hashempur, M.H.; Homayouni, K.; Ashraf, A.; Salehi, A.; Taghizadeh, M.; Heydari, M. Effect of Linum usitatissimum L. (linseed) oil on mild and moderate carpal tunnel syndrome: A randomized, double-blind, placebo-controlled clinical trial. Daru, 2014, 22(1), 43.
[] [PMID: 24386961]
Shim, Y.Y.; Gui, B.; Wang, Y.; Reaney, M.J.T. Flaxseed (Linum usitatissimum L.) oil processing and selected products. Trends Food Sci. Technol., 2015, 43(2), 162-177.
Shim, Y.Y.; Gui, B.; Arnison, P.G.; Wang, Y.; Reaney, M.J.T. Flaxseed (Linum usitatissimum L.) bioactive compounds and peptide nomenclature: A review. Trends Food Sci. Technol., 2014, 38(1), 5-20.
Power, K.A.; Lepp, D.; Zarepoor, L.; Monk, J.M.; Wu, W.; Tsao, R.; Liu, R. Dietary flaxseed modulates the colonic microenvironment in healthy C57Bl/6 male mice which may alter susceptibility to gut-associated diseases. J. Nutr. Biochem., 2016, 28, 61-69.
[ ] [PMID: 26878783]
Oomah, B.D. Flaxseed as a functional food source. J. Sci. Food Agric., 2001, 81(9), 889-894.
Ferhat, R.; Bribi, N.; Merakeb, M.S.; Betitra, Y. Anti-inflammatory and analgesic effect of an alkaloid-fixed oil mix from Linum usitatisimum seeds in vivo. GABJ, 2021, 5(2), 68-76.
Merakeb, M.S.; Bribi, N.; Ferhat, R.; Yanat, B. Inhibitory effects of Linum usitatissimum alkaloid on inflammatory and nociceptive responses in mice. Curr. Bioact. Compd., 2022, 19(2), 56-62.
Soušek, J.; Guédon, D.; Adam, T.; Bochořáková, H.; Táborská, E.; Válka, I.; Šimánek, V. Alkaloids and organic acids content of eightFumaria species. Phytochem. Anal., 1999, 10(1), 6-11.
Rachmilewitz, D.; Karmel, F.; Takabayash, K.; Hayash, T.; Leider-trejo, L.; Lee, J.; Leoni, L.M.; Raz, E. Immunostimulatory DNA ameliorates experimental and spontaneous murine colitis. Gastroenterology, 2002, 122(5), 1428-1441.
Rodríguez-Nogales, A.; Algieri, F.; Vezza, T.; Garrido-Mesa, N.; Olivares, M.; Comalada, M.; Riccardi, C.; Utrilla, M.P.; Rodríguez-Cabezas, M.E.; Galvez, J. The viability of Lactobacillus fermentum CECT5716 is not essential to exert intestinal anti-inflammatory properties. Food Funct., 2015, 6(4), 1176-1184.
[] [PMID: 25700085]
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.
[] [PMID: 2914642]
Zingarelli, B.; Squadrito, F.; Graziani, P.; Camerini, R.; Caputi, A.P. Effects of zileuton, a new 5-lipoxygenase inhibitor, in experimentally induced colitis in rats. Agents Actions, 1993, 39(3-4), 150-156.
[] [PMID: 7905704]
Algieri, F.; Rodriguez-Nogales, A.; Garrido-Mesa, J.; Camuesco, D.; Vezza, T.; Garrido-Mesa, N.; Utrilla, P.; Rodriguez-Cabezas, M.E.; Pischel, I.; Galvez, J. Intestinal anti-inflammatory activity of calcium pyruvate in the TNBS model of rat colitis: Comparison with ethyl pyruvate. Biochem. Pharmacol., 2016, 103, 53-63.
[] [PMID: 26774455]
Garrido-Mesa, J.; Algieri, F.; Rodriguez-Nogales, A.; Utrilla, M.P.; Rodriguez-Cabezas, M.E.; Zarzuelo, A.; Ocete, M.A.; Garrido-Mesa, N.; Galvez, J. A new therapeutic association to manage relapsing experimental colitis: Doxycycline plus Saccharomyces boulardii. Pharmacol. Res., 2015, 97, 48-63.
[] [PMID: 25917208]
Bribi, N.; Rodríguez-Nogales, A.; Vezza, T.; Algieri, F.; Rodriguez-Cabezas, M.E.; Garrido-Mesa, J.; Gálvez, J. Intestinal anti-inflammatory activity of the total alkaloid fraction from Fumaria capreolata in the DSS model of colitis in mice. Bioorg. Med. Chem. Lett., 2020, 30(18), 127414.
[] [PMID: 32717615]
Wirtz, S.; Neufert, C.; Weigmann, B.; Neurath, M.F. Chemically induced mouse models of intestinal inflammation. Nat. Protoc., 2007, 2(3), 541-546.
[] [PMID: 17406617]
Nakhai, L.A.; Mohammadirad, A.; Yasa, N.; Minaie, B.; Nikfar, S.; Ghazanfari, G.; Zamani, M.J.; Dehghan, G.; Jamshidi, H.; Boushehri, V.S.; Khorasani, R.; Abdollahi, M. Benefits of Zataria multiflora Boiss in experimental model of mouse inflammatory bowel disease. Evid. Based Complement. Alternat. Med., 2007, 4(1), 43-50.
[] [PMID: 17342240]
Niu, X.; Fan, T.; Li, W.; Huang, H.; Zhang, Y.; Xing, W. Protective effect of sanguinarine against acetic acid-induced ulcerative colitis in mice. Toxicol. Appl. Pharmacol., 2013, 267(3), 256-265.
[] [PMID: 23352506]
Essel, L.B.; Obiri, D.D.; Osafo, N.; Antwi, A.O.; Duduyemi, M.B. Ulcerative colitis induced with acetic acid is ameliorated by antrocaryon micraster through reduced serum levels of tumor necrosis factor alpha and interleukin 6 in sprague dawley rats. Pharmacognosy Res., 2020, 12(1), 85-91.
Gupta, M.; Mishra, V.; Gulati, M.; Kapoor, B.; Kaur, A.; Gupta, R.; Tambuwala, M.M. Natural compounds as safe therapeutic options for ulcerative colitis. Inflammopharmacology, 2022, 30(2), 397-434.
[] [PMID: 35212849]
Langmead, L.; Rampton, D.S. Review article: Complementary and alternative therapies for inflammatory bowel disease. Aliment. Pharmacol. Ther., 2006, 23(3), 341-349.
[] [PMID: 16422993]
Morsi, E.A.; Ahmed, H.O.; Abdel-Hady, H.; El-Sayed, M.; Shemis, M.A. GC-analysis, and antioxidant, anti-inflammatory, and anticancer activities of some extracts and fractions of Linum usitatissimum. Curr. Bioact. Compd., 2020, 16(9), 1306-1318.
Raghad, J.; Agha, I.H.M. Lipoxygenase inhibitory activity of some extracts prepared from flaxseed (Linum usitatissimumv L.). Curr. Bioact. Compd., 2022, 16(3), 65-71.
Ebrahimi Vosta Kalaee, S.; Talebi Mazraeh Shahi, A.; Naseri, M. Anti-inflammation effect of alcoholic extract of Linum usitatissimum l. in male rats. Majallah-i Danishgah-i Ulum-i Pizishki-i Babul, 2014, 16(4), 50-56.
Ansari, R.; Zarshenas, M.M.; Dadbakhsh, A.H. A review on pharmacological and clinical aspects of Linum usitatissimum L. Curr. Drug Discov. Technol., 2019, 16(2), 148-158.
[] [PMID: 29779483]
Thamilmarai, S.B.; Sathammai, N.T.; Steffi, P.F.; Priyadarshni, S. Phytochemical evaluation, Gc-Ms analysis of phytoactive compounds, and antibacterial activity studies from Linum usitatissimum. Asian J. Pharm. Clin. Res., 2019, 12(8), 141-149.
Palla, A.H.; Iqbal, N.T.; Minhas, K.; Gilani, A.H. Flaxseed extract exhibits mucosal protective effect in acetic acid induced colitis in mice by modulating cytokines, antioxidant and antiinflammatory mechanisms. Int. Immunopharmacol., 2016, 38, 153-166.
[] [PMID: 27280586]
Palla, A.H.; Gilani, A.H.; Bashir, S.; Ur Rehman, N. Multiple mechanisms of flaxseed: Effectiveness in inflammatory bowel disease. Evid. Based Complement. Alternat. Med., 2020, 2020, 1-16.
[] [PMID: 32765633]
Khan, Z.J.; Khan, N.A.; Naseem, I.; Nami, S.A.A. Exploration of physicochemical and phytochemical potential of Linum usitatissmum Linn (Tukhm-e-Katan). Asian J. Pharm. Pharmacol., 2019, 5(3), 551-558.
Goyal, M.; Ghosh, M.; Nagori, B.P.; Sasmal, D. Analgesic and anti-inflammatory studies of cyclopeptide alkaloid fraction of leaves of Ziziyphus nummularia. Saudi J. Biol. Sci., 2013, 20(4), 365-371.
[] [PMID: 24235873]
Dahiya, R.; Dahiya, S. Natural bioeffective cyclooligopeptides from plant seeds of Annona genus. Eur. J. Med. Chem., 2021, 214, 113221.
[] [PMID: 33540356]
Shaukat, B.; Mehmood, M.H. Shahid Shah, ; Anwar, H. Ziziphus oxyphylla hydro-methanolic extract ameliorates hypertension in L-NAME induced hypertensive rats through NO/cGMP pathway and suppression of oxidative stress related inflammatory biomarkers. J. Ethnopharmacol., 2022, 285, 114825.
[] [PMID: 34774683]
Zimmermann, M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain, 1983, 16(2), 109-110.
[] [PMID: 6877845]

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