Generic placeholder image

Current Bioactive Compounds


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

Research Article

Inhibitory Effects of Linum usitatissimum Alkaloid on Inflammatory and Nociceptive Responses in Mice

Author(s): Mohamed Sofiane Merakeb, Noureddine Bribi*, Riad Ferhat and Betitera Yanat

Volume 19, Issue 2, 2023

Published on: 03 September, 2022

Article ID: e270422204128 Pages: 7

DOI: 10.2174/1573407218666220427114432

Price: $65


Background: Linum usitatissimum is widely used in traditional medicine for the treatment of inflammation, and cardiovascular and respiratory diseases.

Methods: Acute oral toxicity and anti-inflammatory and analgesic effects of total alkaloid extract from Linum usitatissimum seeds (ALU) were investigated in vivo. Xylene-induced ear edema was used to determine the anti-inflammatory effect, and acetic acid-induced writhing, formalin-induced paw licking, and tail-immersion tests were used to investigate the analgesic activity.

Results: Oral administration of ALU (50, 100, and 200 mg/kg) produced anti-inflammatory and analgesic effects. ALU significantly diminished the edema induced by xylene. ALU also significantly reduced the abdominal construction induced by acetic acid. Furthermore, ALU also inhibited responses in both phases of formalin-induced paw licking and increased the reaction time of mice in the tail-immersion test.

Conclusion: These findings suggest the total alkaloid extract from Linum usitatissimum seeds presents significant anti-inflammatory and analgesic effects on chemical, behavioral models of inflammation and nociception in mice.

Keywords: Inflammation, anti-inflammatory, analgesic, Linum usitatissimum, alkaloid, seeds.

Graphical Abstract
Oomah, B.D. Flaxseed as a functional food source. J. Sci. Food Agric., 2001, 81(9), 889-894.
Wakjira, A.; Labuschagne, M.T.; Hugo, A. Variability in oil content and fatty acid composition of ethiopian and introduced cultivars of linseed. J. Sci. Food Agric., 2004, 84(6), 601-607.
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]
He, L.; Kim, J.A.; Whistler, J.L. Biomarkers of morphine tolerance and dependence are prevented by morphine-induced endocytosis of a mutant mu-opioid receptor. FASEB J., 2009, 23(12), 4327-4334.
[] [PMID: 19679639]
Piyanuch, R.; Sukhthankar, M.; Wandee, G.; Baek, S.J. Berberine, a natural isoquinoline alkaloid, induces NAG-1 and ATF3 expression in human colorectal cancer cells. Cancer Lett., 2007, 258(2), 230-240.
[] [PMID: 17964072]
Jin, S.J.; Yang, Y.; Ma, L.; Ma, B.H.; Ren, L.P.; Guo, L.C.; Wang, W.B.; Zhang, Y.X.; Zhao, Z.J.; Cui, M. In vivo and in vitro induction of the apoptotic effects of oxysophoridine on colorectal cancer cells via the Bcl-2/Bax/caspase-3 signaling pathway. Oncol. Lett., 2017, 14(6), 8000-8006.
[] [PMID: 29344242]
Patton, H.D. Textbook of Physiology. 21st Edition, Two Volumes. Edited by H. D. Patton, A. F. Fuchs, B. Hille, A. M. Scher and R. Steiner. Vol. 1, Pp. 769 (1–769); Vol. 2, Pp. 826 (771–1596). (Harcourt Brace Jovanovich, 1989.) Each Volume £64.00 Hardback. Vol. 1 ISBN. Exp. Physiol, 1990, 75(2) 281 Available from:
Talwar, S.; Nandakumar, K.; Nayak, P.G.; Bansal, P.; Mudgal, J.; Mor, V.; Rao, C.M.; Lobo, R. Anti-inflammatory activity of Terminalia paniculata bark extract against acute and chronic inflammation in rats. J. Ethnopharmacol., 2011, 134(2), 323-328.
[] [PMID: 21182924]
Sowemimo, A.; Onakoya, M.; Fageyinbo, M.S.; Fadoju, T. Studies on the anti-inflammatory and anti-nociceptive properties of blepharis maderaspatensis leaves. Rev. Bras. Farmacogn., 2013, 23(5), 830-835.
Zhang, J.; Wen, C.; Duan, Y.; Zhang, H.; Ma, H. Advance in Cordyceps militaris (Linn) Link polysaccharides: Isolation, structure, and bioactivities: A review. Int. J. Biol. Macromol., 2019, 132, 906-914.
[] [PMID: 30954592]
Chandrasoma, P.; Taylor, C.R. (Eds.) General Pathology, Section II. The Host Response to Injury.The Acute Inflammatory Response, Sub-Section Cardinal Clinical Signs, Concise Pathology. Part A. Concise Pathol; , 2005.
Shabbir, A.; Batool, S.A.; Basheer, M.I.; Shahzad, M.; Sultana, K.; Tareen, R.B.; Iqbal, J. Saeed-Ul-Hassan, Ziziphora clinopodioides ameliorated rheumatoid arthritis and inflammatory paw edema in different models of acute and chronic inflammation. Biomed. Pharmacother., 2018, 97(97), 1710-1721.
[] [PMID: 29793335]
Zimmermann, M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain, 1983, 16(2), 109-110.
[] [PMID: 6877845]
Soušek, J.; Guédon, D.; Adam, T. Bochoáková, H.; Táborská, E.; Válka, I.; Šimánek, V. Alkaloids and organic acids content of eight fumaria species. Phytochem. Anal., 1999, 10(1), 6-11.
Parveen, Z.; Deng, Y.; Saeed, M.K.; Dai, R.; Ahamad, W.; Yu, Y.H. Antiinflammatory and analgesic activities of Thesium chinense Turcz extracts and its major flavonoids, kaempferol and kaempferol-3-O-glucoside. Yakugaku Zasshi, 2007, 127(8), 1275-1279.
[] [PMID: 17666881]
Silva, C.R.; Oliveira, S.M.; Rossato, M.F.; Dalmolin, G.D.; Guerra, G.P.; da Silveira Prudente, A.; Cabrini, D.A.; Otuki, M.F.; André, E.; Ferreira, J. The involvement of TRPA1 channel activation in the inflammatory response evoked by topical application of cinnamaldehyde to mice. Life Sci., 2011, 88(25-26), 1077-1087.
[] [PMID: 21466812]
Nakamura, H.; Shimoda, A.; Ishii, K.; Kadokawa, T. Central and peripheral analgesic action of non-acidic non-steroidal anti-inflammatory drugs in mice and rats. Arch. Int. Pharmacodyn. Ther., 1986, 282(1), 16-25.
[PMID: 3767523]
Oh, Y.C.; Jeong, Y.H.; Cho, W.K.; Ha, J.H.; Gu, M.J.; Ma, J.Y. Anti-inflammatory and analgesic effects of pyeongwisan on LPS-stimulated murine macrophages and mouse models of acetic acid-induced writhing response and xylene-induced ear edema. Int. J. Mol. Sci., 2015, 16(1), 1232-1251.
[] [PMID: 25569097]
Hunskaar, S.; Hole, K. The formalin test in mice: Dissociation between inflammatory and non-inflammatory pain. Pain, 1987, 30(1), 103-114.
[] [PMID: 3614974]
Tjølsen, A.; Berge, O-G.; Hunskaar, S.; Rosland, J.H.; Hole, K. The formalin test: An evaluation of the method. Pain, 1992, 51(1), 5-17.
[] [PMID: 1454405]
Hunskaar, S.; Fasmer, O.B.; Hole, K. Formalin test in mice, a useful technique for evaluating mild analgesics. J. Neurosci. Methods, 1985, 14(1), 69-76.
[] [PMID: 4033190]
Sewell, R.D.E.; Spencer, P.S.J. Anti-nociceptive activity of narcotic agonists and partial agonists in mice given biogenic amines by intracerebroventricular injection. Psychopharmacology (Berl.), 1975, 42(1), 67-71.
[] [PMID: 1153624]
Ramabadran, K.; Bansinath, M.; Turndorf, H.; Puig, M.M. Tail immersion test for the evaluation of a nociceptive reaction in mice. Methodological considerations. J. Pharmacol. Methods, 1989, 21(1), 21-31.
[] [PMID: 2704245]
Lu, H.M.; Liang, Y.Z.; Yi, L.Z.; Wu, X.J. Anti-inflammatory effect of Houttuynia cordata injection. J. Ethnopharmacol., 2006, 104(1-2), 245-249.
[] [PMID: 16213118]
Jacobs, R.S.; Culver, P.; Langdon, R.; O’Brien, T.; White, S. Some pharmacological observations on marine natural products. Tetrahedron, 1985, 41(6), 981-984.
Rosa, A.C.; Fantozzi, R. The role of histamine in neurogenic inflammation. Br. J. Pharmacol., 2013, 170(1), 38-45.
[] [PMID: 23734637]
Agbaje, E.; Fageyinbo, M. Evaluating anti-inflammatory activity of aqueous root extract of strophanthus hispidus DC. (Apocynaceae). Int. J. Appl. Res. Nat. Prod., 2011, 4, 7-14.
Guo, D.; Xu, L.; Cao, X.; Guo, Y.; Ye, Y.; Chan, C.O.; Mok, D.K.W.; Yu, Z.; Chen, S. Anti-inflammatory activities and mechanisms of action of the petroleum ether fraction of Rosa multiflora Thunb. hips. J. Ethnopharmacol., 2011, 138(3), 717-722.
[] [PMID: 22019508]
Le Bars, D.; Gozariu, M.; Cadden, S.W. Animal models of nociception. Pharmacol. Rev., 2001, 53(4), 597-652.
[PMID: 11734620]
Bribi, N. Anti-nociceptive and anti-inflammatory effects of paeonia mascula extract. J. Pharm. Pharmacogn. Res., 2018, 6(2), 81-88.
Bentley, G.A.; Newton, S.H.; Starr, J. Studies on the antinociceptive action of alpha-agonist drugs and their interactions with opioid mechanisms. Br. J. Pharmacol., 1983, 79(1), 125-134.
[] [PMID: 6135474]
Ikeda, Y.; Ueno, A.; Naraba, H.; Oh-ishi, S. Involvement of vanilloid receptor VR1 and prostanoids in the acid-induced writhing responses of mice. Life Sci., 2001, 69(24), 2911-2919.
[] [PMID: 11720094]
Trongsakul, S.; Panthong, A.; Kanjanapothi, D.; Taesotikul, T. The analgesic, antipyretic and anti-inflammatory activity of diospyros variegata Kruz. J. Ethnopharmacol. 2003, 85(2-3), 221-225.
Gerhard Wolfgang, H. Vogel; Schölkens, Bernward A.; Sandow, Jürgen; Müller, PD Günter; V., W. F., Eds.; Drug Discovery and Evaluation; Springer , 2002.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy