The Relaxant Effect of Plantago Major on Rat Tracheal Smooth Muscles and Its Possible Mechanisms
This study was conducted to evaluate the possible mechanisms of the relaxant effects of hydroalcoholic extract of Plantago major (P. major) on tracheal smooth muscle (TSM) in rats.
The effects of cumulative concentrations of P. major (5, 10, 20 and 40 mg/mL) and theophylline (0.2, 0.4, 0.6 and 0.8 mM) were evaluated on pre-contracted TSM with 10 μΜ methacholine or 60 mM KCl. To determine the possible mechanisms, the relaxant effect of the plant was also examined on incubated TSM with atropine, indomethacin, chlorpheniramine, glibenclamide, diltiazem, papaverine, and propranolol.
The results indicated concentration-dependent relaxant effects for P. major in non-incubated TSM contracted by methacholine or KCl. There was no statistically significant difference in the relaxant effects of P. major between non-incubated and incubated tissues with indomethacin, papaverine, and propranolol. However, the relaxant effects of P. major in incubated tissues with atropine (p<0.01 to p<0.001), chlorpheniramine (p<0.05 to p<0.001), glibenclamide (p<0.05), or diltiazem (p<0.01) were significantly lower than non-incubated TSM.
P. major indicated relatively potent relaxant effects which were lower than those of theophylline. Muscarinic and histamine (H1) receptors inhibition, as well as calcium channel blocking and potassium channel opening effects are suggested to contribute to the TSM relaxant effect of the plant.
2. Samuelsen AB. The traditional uses, chemical constituents and biological activities of Plantago major L. A review. J Ethnopharmacol. 2000;71(1):1-21.
3. Cavers PB, Bassett IJ, Crompton CW. The biology of Canadian weeds.: 47. Plantago lanceolata L. Can J Plant Sci. 1980;60(4):1269-82.
4. Nazarizadeh A, Mikaili P, Moloudizargari M, Aghajanshakeri S, Javaherypour S. Therapeutic uses and pharmacological properties of Plantago major L. and its active constituents. J Basic Appl Sci Res. 2013;3(9):212-21.
5. Abd-Razik B, Hasan H, Murtadha M. The study of antibacterial activity of Plantago major and ceratonia siliqua. Iraq Postgrad Med J. 2012;11(1):130-5.
6. Türel I, Özbek H, Erten R, Öner AC, Cengiz N, Yilmaz O. Hepatoprotective and anti-inflammatory activities of Plantago major L. Indian J Pharmacol. 2009;41(3):120.
7. Kobeasy I, Abdel-Fatah M, El-Salam SMA, Mohamed ZE-OM. Biochemical studies on Plantago major L. and Cyamopsis tetragonoloba L. Int J Biodivers Conserv. 2011;3(3):83-91.
8. Cogo LL, Monteiro CLB, Miguel MD, Miguel OG, Cunico MM, Ribeiro ML, et al. Anti-Helicobacter pylori activity of plant extracts traditionally used for the treatment of gastrointestinal disorders. Braz J Microbiol. 2010;41(2):304-9.
9. Gomez‐Flores R, Calderon C, Scheibel L, Tamez‐Guerra P, Rodriguez‐Padilla C, Tamez‐Guerra R, et al. Immunoenhancing properties of Plantago major leaf extract. Phytother Res. 2000;14(8):617-22.
10. Adom MB, Taher M, Mutalabisin MF, Amri MS, Kudos MBA, Sulaiman MWAW, et al. Chemical constituents and medical benefits of Plantago major. Biomed Pharmacother. 2017;96:348-60.
11. Tarvainen M, Suomela J-P, Kallio H, Yang B. Triterpene acids in Plantago major: Identification, quantification and comparison of different extraction methods. Chromatographia. 2010;71(3-4):279-84.
12. Liu J. Pharmacology of oleanolic acid and ursolic acid. J Ethnopharmacol. 1995;49(2):57-68.
13. Guil-Guerrero JL, Rodríguez-García I. Lipids classes, fatty acids and carotenes of the leaves of six edible wild plants. Eur Food Res Technol. 1999;209(5):313-6.
14. Samuelsen AB, Paulsen BS, Wold JK, Otsuka H, Yamada H, Espevik T. Isolation and partial characterization of biologically active polysaccharides from Plantago major L. Phytother Res. 1995;9(3):211-8.
15. Verma S, Singh S. Current and future status of herbal medicines. Vet World. 2008;1(11):347-50.
16. Farokhi F, Khaneshi F. Histophatologic changes of lung in asthmatic male rats treated with hydro-alcoholic extract of Plantago major and theophylline. Avicenna J Phytomed. 2013;3(2):143.
17. Saadat S, Boskabadi J, Boskabady MH. Contribution of potassium channels, beta2-adrenergic and histamine H1 receptors in the relaxant effect of baicalein on rat tracheal smooth muscle. Iran J Basic Med Sci. 2019;22(11):1347-52.
18. Ozaslan M, Didem Karagöz I, Kalender ME, Kilic IH, Sari I, Karagöz A. In vivo antitumoral effect of Plantago major L. extract on Balb/C mouse with Ehrlich ascites tumor. Am J Chinese Med. 2007;35(05):841-51.
19. Memarzia A, Amin F, Saadat S, Jalali M, Ghasemi Z, Boskabady MH. The contribution of beta-2 adrenergic, muscarinic and histamine (H1) receptors, calcium and potassium channels and cyclooxygenase pathway in the relaxant effect of Allium cepa L. on the tracheal smooth muscle. J Ethnopharmacol. 2019;241:112012.
20. Linden A, Bergendal A, Ullman A, Skoogh B-E, Löfdahl C-G. Salmeterol, formoterol, and salbutamol in the isolated guinea pig trachea: differences in maximum relaxant effect and potency but not in functional antagonism. Thorax. 1993;48(5):547-53.
21. Popa VT, Somani P, Simon V. The effect of inhaled verapamil on resting bronchial tone and airway contractions induced by histamine and acetylcholine in normal and asthmatic subjects 1–4. Am Rev Respir Dis. 1984;130(6):1006-13.
22. Miyahara Y, Kizawa Y, Sano M, Murakami H. Effects of organic and inorganic Ca2+-antagonists on acetylcholine-induced contraction in molluscan (Mytilus edulis) smooth muscle. Gen Pharmacol. 1993;24(6):1419-23.
23. Buckle D, Arch J, Bowring N, Foster K, Taylor J, Taylor S, et al. Relaxant effects of the potassium channel activators BRL 38227 and pinacidil on guinea-pig and human airway smooth muscle, and blockade of their effects by glibenclamide and BRL 31660. Pulm Pharmacol. 1993;6(1):77-86.
24. Lronards B, Rampart M, Herman A. Selective M3 muscarinic receptor inhibit smooth muscle contraction in rabit trachea without increasing the release of acetylcholine. J Pharmacol Exp Ther. 1992;263:770-3.
25. Boskabady MH, Boroushaki M, Aslani MR. Relaxant effect of Portulaca oleraceae on guinea pig tracheal chains and its possible mechanism (s) of action. Med Hypotheses Res. 2004;1:139-47.
26. Danser A, Tom B, De Vries R, Saxena PR. L‐NAME‐resistant bradykinin‐induced relaxation in porcine coronary arteries is NO‐dependent: effect of ACE inhibition. Br J Pharmacol. 2000;131(2):195-202.
27. Shimizu K, Yoshihara E, Takahashi M, Gotoh K, Orita S, Urakawa N, et al. Mechanism of relaxant response to papaverine on the smooth muscle of non-pregnant rat uterus. J Smooth Muscle Res. 2000;36(3):83-91.
28. Slattery MM, Friel AM, Healy DG, Morrison JJ. Uterine relaxant effects of cyclooxygenase-2 inhibitors in vitro. Obstet Gynecol. 2001;98(4):563-9.
29. Satoh K, Yamada H, Taira N. Differential antagonism by glibenclamide of the relaxant effects of cromakalim, pinacidil and nicorandil on canine large coronary arteries. Naunyn Schmiedebergs Arch Pharmacol. 1991;343(1):76-82.
30. Semenov I, Brenner R. Voltage effects on muscarinic acetylcholine receptor‐mediated contractions of airway smooth muscle. Physiol Rep. 2018;6(17):13856.
31. Fukunaga K, Kume H, Oguma T, Shigemori W, Tohda Y, Ogawa E, et al. Involvement of Ca2+ signaling in the synergistic effects between muscarinic receptor antagonists and β2-adrenoceptor agonists in airway smooth muscle. Int J Mol Sci. 2016;17(9):1590.
32. Oenema TA, Kolahian S, Nanninga JE, Rieks D, Hiemstra PS, Zuyderduyn S, et al. Pro-inflammatory mechanisms of muscarinic receptor stimulation in airway smooth muscle. Respir Res. 2010;11(1):130.
33. Gosens R, Rieks D, Meurs H, Ninaber DK, Rabe KF, Nanninga J, et al. Muscarinic M3 receptor stimulation increases cigarette smoke-induced IL-8 secretion by human airway smooth muscle cells. Eur Respir J. 2009;34(6):1436-43.
34. Thangam EB, Jemima EA, Singh H, Bag MS, Khan M, Mathias C, et al. The role of histamine and histamine receptors in mast cell-mediated allergy and inflammation: the hunt for new therapeutic targets. Front Immunol. 2018;9:1873.
35. Yazdian MA, Khodadoost M, Gheisari M, Kamalinejad M, Ehsani AH. A hypothesis on the possible potential of Plantago major in the treatment of urticaria. Galen Med J. 2014;3(2):123-6.
36. Stenholm Å, Göransson U, Bohlin L. Bioassay‐guided supercritical fluid extraction of cyclooxygenase‐2 inhibiting substances in Plantago major L. Phytochem Analysis. 2013;24(2):176-83.
37. Vogelzang S, Prins H. Patch clamp analysis of the dominant plasma membrane K+ channel in root cell protoplasts of Plantago media L. Its significance for the P and K state. J Membr Biol. 1994;141(2):113-22.
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