Gastroprotective effects of both aqueous and ethanolic extracts of Lemon verbena leaves against indomethacin-induced gastric ulcer in rats

Document Type : Short Communication

Authors

1 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Targeted Drug Delivery Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Regarding Lemon verbena gastroprotective effects, we investigated the protective effects of Lemon verbena extracts on reducing gastric ulcer induced by indomethacin.
Materials and Methods: Rats received aqueous and ethanolic extracts of Lemon verbena (50, 100, and 200 mg/kg), zileuton (100 mg/kg), montelukast (10 mg/kg), or 1% Tween 80 in presence or absence of indomethacin (100 mg/kg).
Results: Indomethacin produced stomach ulcer and increased neutrophils percentage and MDA level compared with the control group (p <0.001). Co-administration of indomethacin and zileuton, montelukast and ethanolic (200 mg/kg) (p <0.001), aqueous extract (200 mg/kg) (p <0.05) reduced ulcer compared with the indomethacin group (p <0.001). Ethanolic extracts (100 and 200 mg/kg) and aqueous extract (200 mg/kg) reduced the MDA level (p <0.001). Ethanolic (50, 100, and 200 mg/kg) and aqueous extracts (200 mg/kg) significantly decreased neutrophils percentage compared with the indomethacin group (p <0.001).
Conclusion: Aqueous and particularly ethanolic extracts of Lemon verbena have protective effects on indomethacin-induced gastric ulcers.

Keywords


1. Kangwan N, Park J-M, Kim E-H, Hahm KB. Quality of healing of gastric ulcers: natural products beyond acid suppression. World J Gastrointest Pathophysiol 2014; 5:40-47.
2. Del Valle J. Peptic ulcer disease and related disorders. Harrisons Principles of Internal Medicine 2005; 16:1746.
3. Zhang B-B, Li Y, Liu X-Q, Wang P-J, Yang B, Bian D-L. Association between vacA genotypes and the risk of duodenal ulcer: a meta-analysis. Mol Biol Rep 2014; 41:7241-7254.
4. Huang J-Q, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. The Lancet 2002; 359:14-22.
5. Yuan Y. Padol It, Hunt Rh. Peptic ulcer disease today. Nat Clin Pract Gastroenterol Hepatol 2006; 3:80-89.
6. Musumba C, Pritchard D, Pirmohamed M. cellular and molecular mechanisms of NSAID‐induced peptic ulcers. Aliment Pharm Ther 2009; 30:517-531.
7. Wallace JL. How do NSAIDs cause ulcer disease?. Baillieres Best Pract Res Clin Gastroenterol 2000; 14:147-159.
8. Hedi H, Norbert G. 5-Lipoxygenase pathway, dendritic cells, and adaptive immunity. J Biomed Biotechnol 2004; 2004:99-105.
9. Damtew B, Marino JA, Fratianne RB, Spagnuolo PJ. Neutrophil lipoxygenase metabolism and adhesive function following acute thermal injury. J Lab Clin Med 1993; 121:328-336.
10. Ewadh M, Al-Bayati N, Ijam A. Role of leukotriene in gastric ulcer induced by acetyl salicylic acid in male rabbits: gastroprotection by montelukast. Adv Life Sci Technol 2015; 28:7-13.
11. Ganguly K, Swarnakar S. Induction of matrix metalloproteinase‐9 and‐3 in nonsteroidal anti‐inflammatory drug‐induced acute gastric ulcers in mice: regulation by melatonin. J Pineal Res 2009; 47:43-55.
12. Shahin NN, Abdelkader NF, Safar MM. A novel role of irbesartan in gastroprotection against indomethacin-induced gastric injury in rats: targeting DDAH/ADMA and EGFR/ERK signaling. Sci Rep 2018; 8:4280.
13. Uotila P, Mannisto J, Simberg N, Hartiala K. Indomethacin inhibits arachidonic acid metabolism via lipoxygenase and cyclo-oxygenase in hamster isolated lungs. Prostaglandins Med 1981; 7:591-599.
14. Gandhi MN, Challa SR, Prasanth P, Gandhi TR. Role of leukotrienes in NSAID induced gastric ulceration and inflammation in wistar rats. Asian Pac J Trop Dis 2012; 2:215-219.
15. Souza M, Lemos HP, Oliveira R, Cunha F. Gastric damage and granulocyte infiltration induced by indomethacin in tumour necrosis factor receptor 1 (TNF-R1) or inducible nitric oxide synthase (iNOS) deficient mice. Gut 2004; 53:791-796.
16. Wallace JL, Keenan CM, Granger DN. Gastric ulceration induced by nonsteroidal anti-inflammatory drugs is a neutrophil-dependent process. Am J Physiol Gastrointest Liver Physiol 1990; 259:G462-G467.
17. Muscará MN, Wallace JL. V. Therapeutic potential of nitric oxide donors and inhibitors. Am J Physiol Gastrointest Liver Physiol 1999; 276:G1313-G1316.
18. Awaad AS, El-Meligy RM, Soliman GA. Natural products in treatment of ulcerative colitis and peptic ulcer. Saudi Chemical Society 2013; 17:101-124.
19. Chanudom L, Tangpong J. Anti-inflammation property of Syzygium cumini (L.) Skeels on indomethacin-induced acute gastric ulceration. Gastroenterol Res Pract 2015; 2015: 343642.
20. Lee Y-C, Cheng C-W, Lee H-J, Chu H-C. Apple polyphenol suppresses indomethacin-induced gastric damage in experimental animals by lowering oxidative stress status and modulating the MAPK signaling pathway. J Med Food 2017; 20:1113-1120.
21. Athaydes BR, Alves GM, de Assis ALEM, Gomes JVD, Rodrigues RP, Campagnaro BP, et al. Avocado seeds (Persea americana Mill.) prevents indomethacin-induced gastric ulcer in mice. Food Res Int 2019; 119:751-760.
22. Zheng H-M, Choi M-J, Kim JM, Cha KH, Lee KW, Park YH, et al. Centella asiatica leaf extract protects against indomethacin-induced gastric mucosal injury in rats. J Med Food 2016; 19:38-46.
23. Quirantes-Pine R, Herranz-Lopez M, Funes L, Borras-Linares I, Micol V, Segura-Carretero A, et al. Phenylpropanoids and their metabolites are the major compounds responsible for blood-cell protection against oxidative stress after administration of Lippia citriodora in rats. Phytomedicine 2013; 20:1112-1118.
24. Casamassima D, Palazzo M, Vizzarri F, Costagliola C, Corino C, Di Costanzo A. Dietary effects of plant extracts, based on verbascoside, lycopene and horseradish on several blood variables and plasma oxidative status in growing rabbits. Livest. Sci 2017; 206:148-153.
25. Lenoir L, Joubert‐Zakeyh J, Texier O, Lamaison JL, Vasson MP, Felgines C. Aloysia triphylla infusion protects rats against dextran sulfate sodium‐induced colonic damage. J Sci Food Agric 2012; 92:1570-1572.
26. Mauriz E, Vallejo D, Tuñón MJ, Rodriguez-López JM, Rodríguez-Pérez R, Sanz-Gómez J, et al. Effects of dietary supplementation with Lemon verbena extracts on serum inflammatory markers of multiple sclerosis patients. Nutr Hosp 2015; 31:764-771.
27. Funes L, Fernández-Arroyo S, Laporta O, Pons A, Roche E, Segura-Carretero A, et al. Correlation between plasma anti-oxidant capacity and verbascoside levels in rats after oral administration of Lemon verbena extract. Food Chem 2009; 117:589-598.
28. Schneider I, Bucar F. Lipoxygenase inhibitors from natural plant sources. Part 1: Medicinal plants with inhibitory activity on arachidonate 5‐lipoxygenase and 5‐lipoxygenase [sol] cyclooxygenase. Phytotherapy research: An international journal devoted to pharmacological and toxicological evaluation of natural product derivatives 2005; 19:81-102.
29. Tiemersma EW, Bronzwaer SL, Lyytikäinen O, Degener JE, Schrijnemakers P, Bruinsma N, et al. Methicillin-resistant Staphylococcus aureus in Europe, 1999–2002. Emerg. Infect. Dis 2004; 10:1627.
30. Singh VP, Patil CS, Kulkarni SK. Effect of licofelone against NSAIDs-induced gastrointestinal ulceration and inflammation. Indian J Exp Biol 2005; 43:247-53.
31. Uchiyama M, Mihara M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Bioanal Chem 1978; 86:271-278.
32. Wallace JL, McKnight GW. Characterization of a simple animal model for nonsteroidal anti-inflammatory drug induced antral ulcer. Can J Physiol Pharm 1993; 71:447-452.
33. El-Ashmawy NE, Khedr EG, El-Bahrawy HA, Selim HM. Nebivolol prevents indomethacin-induced gastric ulcer in rats. J Immunotoxicol 2016; 13:580-589.
34. Docherty JC, Wilson TW. Indomethacin increases the formation of lipoxygenase products in calcium ionophore stimulated human neutrophils. Biochem Bioph Res Co 1987; 148:534-538.
35. Itoh K, Yamamoto K, Adachi M, Kosaka T, Tanaka Y. Leukotriene B4 12-hydroxydehydrogenase/15-ketoprostaglandin Δ 13-reductase (LTB4 12-HD/PGR) responsible for the reduction of a double-bond of the α, β-unsaturated ketone of an aryl propionic acid non-steroidal anti-inflammatory agent CS-670. Xenobiotica 2008; 38:249-263.
36. Hori T, Yokomizo T, Ago H, Sugahara M, Ueno G, Yamamoto M, et al. Structural basis of leukotriene B4 12-hydroxydehydrogenase/15-Oxo-prostaglandin 13-reductase catalytic mechanism and a possible Src homology 3 domain binding loop. J Biol Chem 2004; 279:22615-22623.
37. Pihan G, Rogers C, Szabo S. Vascular injury in acute gastric mucosal damage. Dig Dis Sci 1988; 33:625-632.
38. Wallace JL, Keenan CM. An orally active inhibitor of leukotriene synthesis accelerates healing in a rat model of colitis. Am J Physiol Gastrointest Liver Physiol 1990; 258:G527-G534.
39. Wallace J, McKnight G. Comparison of the damage-promoting effects of leukotrienes derived from eicosapentaenoic acid and arachidonic acid on the rat stomach. J Exp Med 1990; 171:1827-1832.
40. Rainsford K. The effects of 5-lipoxygenase inhibitors and leukotriene antagonists on the development of gastric lesions induced by nonsteroidal antiinflammatory drugs in mice. Agents Actions 1987; 21:316-319.
41. Ozbakış-Dengiz G, Cadırcı E, Yurdakan G. Histopathologic evaluation of anti-ulcerogenic effect of montelukast in indomethacin-induced experimental ulcer model. Turk J Gastroenterol 2013; 24:88-92.
42. Goodman L, Coles T, Budsberg S. Leukotriene inhibition in small animal medicine. J Vet Pharmacol Ther 2008; 31:387-398.
43. Rainsford K. Leukotrienes in the pathogenesis of NSAID-induced gastric and intestinal mucosal damage. Agents  Actions 1993; 39:C24-C26.
44. Abdel‐Raheem IT. Gastroprotective effect of rutin against indomethacin‐induced ulcers in rats. Basic Clin Pharmacol 2010; 107:742-750.
45. Dengiz GO, Odabasoglu F, Halici Z, Cadirci E, Suleyman H. Gastroprotective and anti-oxidant effects of montelukast on indomethacin-induced gastric ulcer in rats. J Pharmacol Sci 2007; 105:94-102.
46. Demircan B, Çelik G, Süleyman H, Akçay F. Effects of indomethacin, celecoxib and meloxicam on glutathione, malondialdehyde and myeloperoxidase in rat gastric tissue. The Pain Clinic 2005; 17:383-388.
47. Turan MI, Bilen H, Demiryilmaz I, Ozgeris FB, Baykal H, Turkoglu M, et al. Effects of Hypericum perforatum and Hippophae rhamnoides extracts on indomethacin-induced gastric oxidative stress in rats. Biomed Res 2013; 24:314-319.
48. Bilia AR, Giomi M, Innocenti M, Gallori S, Vincieri FF. HPLC–DAD–ESI–MS analysis of the constituents of aqueous preparations of verbena and Lemon verbena and evaluation of the anti-oxidant activity. J Pharmaceut Biomed 2008; 46:463-470.
49. Born M, Carrupt PA, Zini R, Brée F, Tillement JP, Hostettmann K, et al. Electrochemical behaviour and anti-oxidant activity of some natural polyphenols. Helv Chim Acta 1996; 79:1147-1158.
50. Obied HK, Prenzler PD, Robards K. Potent anti-oxidant biophenols from olive mill waste. Food Chem 2008; 111:171-178.
51. Rice-Evans CA, Miller NJ, Paganga G. Structure anti-oxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20:933-956.
52. Funes L, Carrera-Quintanar L, Cerdán-Calero M, Ferrer MD, Drobnic F, Pons A, et al. Effect of Lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils’ oxidative stress in chronic exercise. Eur J Appl Physiol 2011; 111:695-705.
53. Tajik J, Kheirandish R, Azizi S, Amanollahi R, Mahmoudi T. The effects of aqueous extracts of Lippia citriodora, trachyspermum copticum, dracocepalum polychaetum on repair of ethanol induced gastric ulcer in rats. Comp Clin Path 2016; 25:119-123.
54. Deepak M, Umashankar D, Handa S. Verbascoside: a promising phenylpropanoid. Indian Drugs 1999; 36:336-345.
55. Speranza L, Franceschelli S, Pesce M, Reale M, Menghini L, Vinciguerra I, et al. Anti inflammatory effects in THP‐1 cells treated with verbascoside. Phytother Res 2010; 24:1398-1404.