Histopathological and biochemical evaluation of the protective efficacy of Prunus spinosa L. extract in a rat model of indomethacin-induced gastric ulcer

Document Type : Original Article

Authors

1 Department of Pharmacology, Faculty of Medicine, Selcuk University, 42131, Konya, Turkey

2 Department of Biochemistry, Faculty of Medicine, Selcuk University, 42131, Konya, Turkey

3 Department of Clinical Pharmacy, Faculty of Pharmacy, Selcuk University, 42100, Konya, Turkey

4 Department of Pathology, Faculty of Medicine, Selcuk University, 42131, Konya, Turkey

5 Department of Biostatistics, Faculty of Medicine, Selcuk University, 42131, Konya, Turkey

6 Research Assistant, Department of Pharmacology, Faculty of Pharmacy, Selcuk University, 42100, Konya, Turkey

7 Research Assistant, Department of Pharmacognosy, Faculty of Pharmacy, Selcuk University, 42100, Konya, Turkey

8 Department of Pharmacognosy, Faculty of Pharmacy, Erciyes University, 38280, Kayseri, Turkey

9 Department of Pharmaceutical Botany, Faculty of Pharmacy, Selcuk University, 42100, Konya, Turkey

10 Department of Pediatrics, Division of Pediatric Gastroenterology, Faculty of Medicine, Selcuk University, 42131, Konya, Turkey

Abstract

Objective(s): Some species of Prunus L. are popularly used to treat gastric ulcers. However, the possible healing mechanisms of the anti-ulcer activity of P. spinosa, which has proven antioxidant, anti-inflammatory, and wound-healing properties, are unclear.
Materials and Methods: Ethanol extracts of P. spinosa fruits were administered orally at 100 mg/kg and 200 mg/kg to Wistar albino rats, with an indomethacin-induced gastric ulcer model. The ulcerous areas on the stomach surface were examined macroscopically. Tissues were examined histopathologically and biochemically. LC-HRMS revealed the phytochemical content.
Results: TNF-α, IL-6, IL-1β, IL-8, and NF-kB levels were higher in the gastric ulcer group than in the extract groups. The VEGF values did not differ in each group. A significant difference was found between the lansoprazole group and the high-dose P. spinosa group regarding PGE2 levels. A histopathologically significant difference was observed between the healthy group and the indomethacin-applied groups in terms of neutrophilic infiltration of the gastric mucosa. Ascorbic acid (1547.521 µg/g), homoprotocatechuic acid (1268.217 µg/g), and genistein (1014.462 µg/g) were found as the main compounds in the P. spinosa extract by LC-HRMS.
Conclusion: Our results demonstrated that P. spinosa protected the gastric mucosa from inflammation and also modulated the PGE2 pathway. When considered in terms of TNF-α, IL-1β, IL-8, IL-6, PGE2, and NF-kB values, it can be concluded that it has a similar or even more positive effect than the reference substance. P. spinosa showed its effects in a dose-dependent manner.

Keywords

Main Subjects

References

1. Périco LL, Emílio-Silva MT, Ohara R, Rodrigues VP, Bueno G, Barbosa-Filho JM, et al. Systematic analysis of monoterpenes: Advances and challenges in the treatment of peptic ulcer diseases. Biomolecules 2020; 10: 265-282.
2. Ahmad AA, Kasim KF, Ma’Radzi AH, Gopinath SC. Peptic ulcer: Current prospects of diagnostic and nanobiotechnological trends on pathogenicity. Process Biochem 2019; 85: 51-59.
3. Lanas A, Chan FK. Peptic ulcer disease. Lancet 2017; 390: 613-624.
4. Li Q, Yang L, Fan L, Liang C, Wang Q, Wen H, et al. Activity of Brucea javanica oil emulsion against gastric ulcers in rodents. Asian J Pharm Sci 2018; 13: 279-288.
5. Wang A, Yerxa J, Agarwal S, Turner MC, Schroder V, Youngwirth LM, et al. Surgical management of peptic ulcer disease. Curr Probl Surg 2020; 57:100728-100728.
6. Malfertheiner P, Schulz C. Peptic ulcer: Chapter closed? Dig Dis 2020; 38: 112-116.
7. Lanas A. We are using too many PPIs, and we need to stop: A European perspective. Am J Gastroenterol 2016; 111:1085-1086.
8. Bjarnason I, Scarpignato C, Holmgren E, Olszewski M, Rainsford KD, Lanas A. Mechanisms of damage to the gastrointestinal tract from nonsteroidal anti-inflammatory drugs. Gastroenterology 2018; 154:500-514.
9. Scally B, Emberson JR, Spata E, Reith C, Davies K, Halls H, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol 2018; 3: 231-241.
10. Vaezi MF, Yang Y-X, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology 2017; 153: 35-48.
11. Ito T, Jensen RT. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B 12, iron, and magnesium. Curr Gastroenterol Rep 2010; 12: 448-457.
12. Waldum HL, Fossmark R. Proton pump inhibitors and gastric cancer: a long expected side effect finally reported also in man. Gut 2018; 67:199-200.
13. Abrahami D, McDonald EG, Schnitzer ME, Barkun AN, Suissa S, Azoulay L. Proton pump inhibitors and risk of gastric cancer: population-based cohort study. Gut 2022; 71:16-24.
14. Lei W-Y, Wang J-H, Yi C-H, Liu T-T, Hung J-S, Wong M-W, et al. Association between use of proton pump inhibitors and colorectal cancer: A nationwide population-based study. Clin Res Hepatol Gastroenterol 2021; 45:101397.
15. Meng R, Chen LR, Zhang ML, Cai WK, Yin SJ, Fan YX, et al. Effectiveness and safety of histamine H2 receptor antagonists: An umbrella review of meta‐analyses. J Clin Pharmacol 2023; 63: 7-20.
16. Zhang W, Lian Y, Li Q, Sun L, Chen R, Lai X, et al. Preventative and therapeutic potential of flavonoids in peptic ulcers. Molecules 2020; 25:4626-4656.
17. Kuna L, Jakab J, Smolic R, Raguz-Lucic N, Vcev A, Smolic M. Peptic ulcer disease: A brief review of conventional therapy and herbal treatment options. J Clin Med 2019; 8:179-197.
18. Marchelak A, Owczarek A, Rutkowska M, Michel P, Kolodziejczyk-Czepas J, Nowak P, et al. New insights into antioxidant activity of Prunus spinosa flowers: Extracts, model polyphenols and their phenolic metabolites in plasma towards multiple in vivo-relevant oxidants. Phytochem Lett 2019; 30:288-295.
19. Marčetić M, Samardžić S, Ilić T, Božić DD, Vidović B. Phenolic composition, antioxidant, anti-enzymatic, antimicrobial and prebiotic properties of Prunus spinosa L. fruits. Foods 2022; 11:3289-3306.
20. Gunes F. Medicinal plants used in the Uzunkopru district of Edirne, Turkey. Acta Soc Bot Pol 2017; 86: 3565-3585.
21. Genç GE, Özhatay N. An ethnobotanical study in Çatalca (European part of Istanbul) II. Turk J Pharm Sci 2006; 3: 73-89.
22. Sikora E, Bieniek MI, Borczak B. Composition and antioxidant properties of fresh and frozen stored blackthorn fruits (Prunus spinosa L.). Acta Sci Pol Technol Aliment 2013; 12:365-372.
23. Sabatini L, Fraternale D, Di Giacomo B, Mari M, Albertini MC, Gordillo B, et al. Chemical composition, antioxidant, antimicrobial and anti-inflammatory activity of Prunus spinosa L. fruit ethanol extract. J Func Food 2020; 67:103885-103894.
24. Veličković JM, Kostić DA, Stojanović GS, Mitić SS, Mitić MN, Ranđelović SS, et al. Phenolic composition, antioxidant and antimicrobial activity of the extracts from Prunus spinosa L. fruit. Hem Ind 2014; 68:297-303.
25. Aydin Berktas O, Keskin A, Gulec Peker EG. Gastroprotective effects of Prunus laurocerasus L. fruit extracts against the oxidative stress induced by indomethacin in rats. Eur J Clin Exp Med 2022; 3: 284-289.
26. Veličković I, Žižak Ž, Rajčević N, Ivanov M, Soković M, Marin PD, et al. Examination of the polyphenol content and bioactivities of Prunus spinosa L. fruit extracts. Arch Biol Sci 2020; 72:105-115.
27. Kisaoglu A, Ozogul B, Cetyn N, Suleyman B, Atamanalp S, Akcay F, et al. The role of Alpha-2 adrenergic receptors in the anti-ulcerative activity of famotidine and omeprazole in rats and its relationship with oxidant-antioxidant parameters. Int J Pharmacol 2011; 7: 682-689.
28. Atalay F, Odabasoglu F, Halici M, Cadirci E, Aydin O, Halici Z, et al. N‐Acetyl cysteine has both gastro‐protective and anti‐inflammatory effects in experimental rat models: its gastro‐protective effect is related to its in vivo and in vitro antioxidant properties. J Cell Biochem 2016; 117: 308-319.
29. Bhattacharya S, Chaudhuri SR, Chattopadhyay S, Bandyopadhyay SK. Healing properties of some Indian medicinal plants against indomethacin-induced gastric ulceration of rats. J Clin Biochem Nutr 2007; 41: 106-114.
30. Becker JC, Grosser N, Boknik P, Schröder H, Domschke W, Pohle T. Gastroprotection by vitamin C--a heme oxygenase-1-dependent mechanism? Biochem Biophys Res Commun 2003; 312: 507-512.
31. Pohle T, Brzozowski T, Becker J, Van der Voort I, Markmann A, Konturek S, et al. Role of reactive oxygen metabolites in aspirin‐induced gastric damage in humans: Gastroprotection by vitamin C. Aliment pharmacol Ther 2001; 15: 677-687.
32. Tang Y, Nakashima S, Saiki S, Myoi Y, Abe N, Kuwazuru S, et al. 3, 4-Dihydroxyphenylacetic acid is a predominant biologically-active catabolite of quercetin glycosides. Food Res Int 2016; 89: 716-723.
33. Kore K, Bramhakule P, Rachhadiya R, Shete R. Evaluation of antiulcer activity of protocatechuic acid ethyl ester in rats. Int J Pharm Life Sci 2011; 2: 909.
34. Abdel-Raheem I,  Bamagous, G, Omran G. Nti-ulcerogenic effect of genistein against indomethacin-induced gastric ulcer in rats. Asian J Pharm Clin Res 2016; 9: 58-63.
35. Vivatvakin S, Werawatganon D, Somanawat K, Klaikeaw N, Siriviriyakul P. Genistein-attenuated gastric injury on indomethacin-induced gastropathy in rats. Pharmacogn Mag 2017; 13: S306-S310.
36. Karakas N, Okur ME, Ozturk I, Ayla S, Karadag AE, Polat DÇ. Antioxidant activity of blackthorn (Prunus spinosa L.) fruit extract and cytotoxic effects on various cancer cell lines. Medeni Med J 2019; 34: 297-304.
37. Ruiz-Rodríguez BM, De Ancos B, Sánchez-Moreno C, Fernández-Ruiz V, de Cortes Sánchez-Mata M, Cámara M, et al. Wild blackthorn (Prunus spinosa L.) and hawthorn (Crataegus monogyna Jacq.) fruits as valuable sources of antioxidants. Fruits 2014; 69: 61-73.
38. Hudson N, Hawthorne A, Cole A, Jones P, Hawkey C. Mechanisms of gastric and duodenal damage and protection. Hepatogastroenterology 1992; 39:31-36.
39. Takeuchi K, Amagase K. Roles of cyclooxygenase, prostaglandin E2 and EP receptors in mucosal protection and ulcer healing in the gastrointestinal tract. Curr Pharm Des 2018; 24: 2002-2011.
40. Suleyman H, Demircan B, Karagoz Y. Anti-inflammatory and side effects of cyclo-oxygenase inhibitors. Pharmacol Rep 2007; 59:247-258.
41. Pinacho R, Cavero RY, Astiasarán I, Ansorena D, Calvo MI. Phenolic compounds of blackthorn (Prunus spinosa L.) and influence of in vitro digestion on their antioxidant capacity. J Funct Food 2015; 19:49-62.
42. Strbo N, Yin N, Stojadinovic O. Innate and adaptive immune responses in wound epithelialization. Adv Wound Care 2014; 3:492-501.
43. Wang Y, Sun Y-w, Wang Y-m, Ju Y, Meng D-l. Virtual screening of active compounds from Artemisia argyi and potential targets against gastric ulcer based on Network pharmacology. Bioorg Chem 2019; 88:102924.
44. Sugimoto M, Yamaoka Y, Furuta T. Influence of interleukin polymorphisms on development of gastric cancer and peptic ulcer. World J Gastroenterol 2010; 16:1188-1200.
45. Liu X, Quan S, Han Q, Li J, Gao X, Zhang J, et al. Effectiveness of the fruit of Rosa odorata sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils in the protection and the healing of ethanol-induced rat gastric mucosa ulcer based on Nrf2/NF-κB pathway regulation. J Ethnopharmacol 2022; 282:114626.
46. Solanki K, Rajpoot S, Bezsonov EE, Orekhov AN, Saluja R, Wary A, et al. The expanding roles of neuronal nitric oxide synthase (NOS1). PeerJ 2022; 10: e13651-13681.
47. Almasaudi SB, El-Shitany NA, Abbas AT, Abdel-Dayem UA, Ali SS, Al Jaouni SK, et al. Antioxidant, anti-inflammatory, and antiulcer potential of manuka honey against gastric ulcer in rats. Oxid Med Cell Longev 2016; 2016: 3643824-3643833.
48. Salvemini D, Kim SF, Mollace V. Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: Relevance and clinical implications. Am J Physiol Regul Integr Comp Physiol 2013; 304:R473-R487.
49. Szlachcic A, Krzysiek-Maczka G, Pajdo R, Targosz A, Magierowski M, Jasnos K, et al. The impact of asymmetric dimethylarginine (ADAMA), the endogenous nitric oxide (NO) synthase inhibitor, to the pathogenesis of gastric mucosal damage. Curr Pharm Des 2013; 19:90-97.
50. De Souza GF, Taladriz-Blanco P, Velloso LA, De Oliveira MG. Nitric oxide released from luminal s-nitroso-N-acetylcysteine increases gastric mucosal blood flow. Molecules 2015; 20:4109-4123.
Iranian Journal of Basic Medical Sciences
Volume 27, Issue 11
November 2024
Pages 1464-1474

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