Evaluation of Gastroprotective Effect from Phaleria macrocarpa Fruits Extract on Gastric Ulcer in Male Wistar Rats
DOI:
https://doi.org/10.3889/oamjms.2022.8242Keywords:
Phaleria macrocarpa, Mahkota Dewa fruit, Gastroprotective, Gastric ulcers, ExtractAbstract
Abstract
BACKGROUND: The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) triggers gastric mucosal damage and causes ulcers. Meanwhile, studies showed that God's crown fruit (Phaleria macrocarpa) contains secondary metabolites of flavonoids and tannins that can protect the gastric mucosa.
AIM: This study aims to determine the gastroprotective effect of P. macrocarpa ethanolic extracts against gastric ulcers in rats induced with acetosal and ethanol. The extracts were obtained by maceration method using 96% ethanol as solvent.
METHODS: The male rats used were divided into 7 groups for each test with ethanol and acetosal induction. Each group consisted of 5 rats, namely normal control, induction, carrier, positive control (sucralfate 360 mg/kg BW and omeprazole 3.6 mg/kg BW), and extract doses 100, 200, and 400 mg/kg body weight. All groups were given treatment for 7 days except normal and induction controls. On day 6, rats were fasted for 36 hours and induced with acetosal/ethanol. In ethanol induction, the animal was sacrificed after 10 hours of immersion while in acetosal, the animal was sacrificed 6 hours later. The stomach section was taken for macroscopic, microscopic parameters and gastric acid secretion examination.
RESULTS: The results of phytochemical screening showed that the extract contained flavonoids, tannins, saponins, alkaloids, and glycosides. In acetosal-induced ulcers, the administration of one dose of the extract reduced the number and score of ulcers, repair epithelial cells, increase pH, and total gastric acidity. Furthermore, the percentage of ulcer inhibition at the extract dose of 400 mg/kg BW was 91.91±3.74% in ethanol induction, and 59±13.08% in acetosal.
CONCLUSION: The ethanolic extract of P. macrocarpa has a gastroprotective effect on acetosal-induced gastric ulcer rats.
Keywords: Phaleria macrocarpa, Mahkota Dewa fruit, gastroprotective, gastric ulcers, extract
Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Allen A, Flemström G. Gastroduodenal mucus bicarbonate barrier: Protection against acid and pepsin. Am J Physiol Cell Physiol 2005;288(1):C1-9. https://doi.org/10.1152/ajpcell.00102.2004 PMid:15591243
Kirsch JM, Hirsch-Reilly C. Peptic ulcer disease. In: Acute Care General Surgery: Workup and Management. Vol. 16. Berlin: Springer; 2017. p. 159-64.
Fujinami H. A study of the changes in the cause of peptic ulcer bleeding. World J Gastrointest Endosc. 2012;4(7):323-7. https://doi.org/10.4253/wjge.v4.i7.323 PMid:22816013
Hunt RH, Bazzoli F. Should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing. Aliment Pharmacol Ther Suppl. 2004;19(Suppl 1):9-16. https://doi.org/10.1111/j.0953-0673.2004.01830.x PMid:14725573
Melcarne L, García-Iglesias P, Calvet X. Management of NSAID-associated peptic ulcer disease. Expert Rev Gastroenterol Hepatol. 2016;10(6):723-33. https://doi.org/10.1586/17474124.2016.1142872 PMid:26775657
Jiao J, Yang Y, Wu Z, Li B, Zheng Q, Wei S, et al. Screening cyclooxygenase-2 inhibitors from Andrographis paniculata to treat inflammation based on bio-affinity ultrafiltration coupled with UPLC-Q-TOF-MS. Fitoterapia. 2019;137:104259. https://doi.org/10.1016/j.fitote.2019.104259 PMid:31319108
Perini R, Ma L, Wallace J. Mucosal repair and COX-2 inhibition. Curr Pharm Des. 2005;9(27):2207-11. https://doi.org/10.2174/1381612033454027 PMid:14529401
Hase S, Yokota A, Nakagiri A, Takeuchi K. Prostaglandin E2 aggravates gastric mucosal injury induced by histamine in rats through EP1 receptors. Life Sci. 2003;74(5):629-41. https://doi.org/10.1016/j.lfs.2003.07.010
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(18):2002-11. https://doi.org/10.2174/1381612824666180629111227 PMid:29956615
Liu J, Wang F, Luo H, Liu A, Li K, Li C, et al. Protective effect of butyrate against ethanol-induced gastric ulcers in mice by promoting the anti-inflammatory, anti-oxidant and mucosal defense mechanisms. Int Immunopharmacol. 2016;30:179-87. https://doi.org/10.1016/j.intimp.2015.11.018 PMid:26604089
Melo JG, Castro PA, Perez LN. Complex mix of Psidium guajava. L as a protector of medicines used in the treatment of gastric ulcer. Free Radic Biol Med. 2018;120:S86.
Narwanto MI, Rahayu M, Soeharto S, Nurdiana N, Moch AW. Identification and in silico analysis of anti-inflammation and anti-oxidant potentials of polyphenol compounds in methanol extract of Tamarindus indica seeds. J Agromed Med Sci. 2018;4:13. https://doi.org/10.19184/ams.v4i1.6735
Jalali Z, Khademalhosseini M, Soltani N, Nadimi AE. Smoking, alcohol and opioids effect on coronary microcirculation: an update overview. BMC Cardiovasc Disord. 2021;21:1-17.
Levine A, Clemenza K, Weiss S, Bisaga A, Eitan E, Gerra MC, et al. Could improved microcirculation reverse the effects of fetal alcohol syndrome? A review. CNS Spectrums. 2021;26:173-3.
Yegen BC. Lifestyle and peptic ulcer disease. Curr Pharm Des. 2018;24(18):2034-40. https://doi.org/10.2174/1381612824666180510092303 PMid:29745325
Simões S, Lopes R, Campos MC, Marruz MJ, da Cruz ME, Corvo L. Animal models of acute gastric mucosal injury: Macroscopic and microscopic evaluation. Anim Mod Exp Med. 2019;2(2):121-6. https://doi.org/10.1002/ame2.12060 PMid:31392305
Hendra R, Haryani Y. Phaleria macrocarpa (Boerl.) Scheff fruit: A potential source of natural antioxidant. Pharmacol Clin Pharm Res. 2018;3:1-4.
Alara OR, Abdul Mudalip SK, Olalere OA. Optimization of mangiferin extrated from Phaleria macrocarpa fruits using response surface methodology. J Appl Res Med Aromat Plants. 2017;5:82-7.
Hendra R, Ahmad S, Oskoueian E, Sukari A, Shukor MY. Antioxidant, anti-inflammatory and cytotoxicity of Phaleria macrocarpa (Boerl.) Scheff fruit. BMC Complement Altern Med. 2011;11:110. https://doi.org/10.1186/1472-6882-11-110 PMid:22070850
Abdel-Tawab MS, Tork OM, Mostafa-Hedeab G, Hassan ME, Elberry DA. Protective effects of quercetin and melatonin on indomethacin induced gastric ulcers in rats. Rep Biochem Mol Biol. 2020;9(3):278. https://doi.org/10.29252/rbmb.9.3.278 PMid:33649721
Li WS, Lin SC, Chu CH, Chang YK, Zhang X, Lin CC, et al. The gastroprotective effect of naringenin against ethanol-induced gastric ulcers in mice through inhibiting oxidative and inflammatory responses. Int J Mol Sci. 2021;22(21):11985. https://doi.org/10.3390/ijms222111985 PMid:34769415
Meiyanti, Dewoto HR, Suyatna FD. [Hypoglycemic effect of mahkota dewa mesocarp fruit (Phaleria macrocarpa (Scheff.) Boerl) on glucose blood level in glucose loading healthy volunteers]. Efek hipoglikemik daging buah Mahkota dewa (Phaleria Macrocarpa (Scheff.) Boerl.) terhadap kadar gula darah pada manusia sehat setelah pembebanan glukosa. Univ Med. 2006;25:114-20.
Havsteen B. Flavonoids, a class of natural products of high pharmacological potency. Biochem Pharmacol. 1983;32:1141-8. https://doi.org/10.1016/0006-2952(83)90262-9 PMid:6342623
Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. J Nutr Sci. 2016;5:e7. https://doi.org/10.1017/jns.2016.41 PMid:28620474
Hässig A, Linag WX, Schwabl H, Stampfli K. Flavonoids and tannins: Plant-based antioxidants with vitamin character. Med Hypotheses. 1999;52(5):479-81. https://doi.org/10.1054/mehy.1997.0686 PMid:10416956
Matsuo T, Itoo S. Comparative studies of condensed tannins from several young fruits. J Jpn Soc Hortic Sci. 1981;50(2): 262-9.
Ge JF, Wang TY, Zhao B, Lv XW, Jin Y, Peng L, et al. Anti-inflammatory effect of triterpenoic acids of Eriobotrya japonica (Thunb.) Lindl. leaf on rat model of chronic bronchitis. Am J Chin Med. 2009;37(2):309-21. https://doi.org/10.1142/S0192415X09006862 PMid:19507274
Gamal G, Abo-El-Seoud KA, Attia G. Triterpenoids from the aerial parts of Anabasis articulata (Forssk) Moq: Gastroprotective effect in vivo with in silico studies, cytotoxic and antimicrobial activities. Nat Prod Res. 2021;12:1-9. https://doi.org/10.1080/14786419.2021.1961769 PMid:34380340
Lee CH, Wu SL, Chen JC, Li CC, Lo HY, Cheng WY, et al. Eriobotrya japonica leaf and its triterpenes inhibited lipopolysaccharide-induced cytokines and inducible enzyme production via the nuclear factor-κB signaling pathway in lung epithelial cells. Am J Chin Med. 2008;36(6):1185-98. https://doi.org/10.1142/S0192415X0800651X PMid:19051345
Huang Y, Li J, Meng XM, Jiang GL, Li H, Cao Q, et al. Effect of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. Leaf and MAPK signal transduction pathway on inducible nitric oxide synthase expression in alveolar macrophage of chronic bronchitis rats. Am J Chin Med. 2009;37(6):1099-111. https://doi.org/10.1142/S0192415X09007521 PMid:19938219
Castro-Vazquez L, Alañón ME, Rodríguez-Robledo V, Pérez- Coello MS, Hermosín-Gutierrez I, Díaz-Maroto MC, et al. Bioactive flavonoids, antioxidant behaviour, and cytoprotective effects of dried grapefruit peels (Citrus paradisi Macf.). Oxid Med Cell Longev. 2016;2016:8915729.
Szabo S. Gastric cytoprotection” is still relevant. J Gastroenterol Hepatol. 2014;29(Suppl 4):124-32. https://doi.org/10.1111/jgh.12735 PMid:25521744
Ministry of Health of the Republic of Indonesia. Directorate General of Drug and Food Control. Materia Medika Indonesia. Vol. 6. Jakarta: Ministry of Health of the Republic of Indonesia; 1995.
Harborn, JB. Phytochemical Methods: A Guide to Modern Techniques of Plant Analysis. 1st ed. Dordrecht: Springer; 1984. https://doi.org/10.1007/978-94-009-5570-7
Mutmainah, Susilowati R, Rahmawati N, Nugroho AE. Gastroprotective effects of combination of hot water extracts of turmeric (Curcuma domestica L.), cardamom pods (Ammomum compactum S.) and sembung leaf (Blumea balsamifera DC.) against aspirin-induced gastric ulcer model in rats. Asian Pac J Trop Biomed. 2014;4(Suppl1):S500-4. https://doi.org/10.12980/APJTB.4.2014C972 PMid:25183139
Sowndhararajan K, Paul S, Kwon GS, Hwang CW, Kang SC. Protective effect of polyamine extract of salt stressed and sprouted soybean seeds against ethanol-induced gastric ulcer in rats. Food Sci Biotechnol. 2014;23:711-6.
Sattar A, Abd A, Musthaq MQ, Anjum I, Anjum A. Evaluation of gastro-protective activity of Myristica fragranson ethanol-induced ulcer in albino rats. Ann Braz Acad Sci. 2019;91:e20181044.
Tan PV, Nditafon NG, Yewah MP, Dimo T, Ayafor FJ. Eremomastax speciosa: Effects of leaf aqueous extract on ulcer formation and gastric secretion in rats. J Ethnopharmacol. 1996;54(2-3):139-42. https://doi.org/10.1016/s0378-8741(96)01461-4 PMid:8953428
Sabiu S, Garuba T, Sunmonu T, Ajani E, Sulyman A, Nurain I, et al. Indomethacin-induced gastric ulceration in rats: Protective roles of Spondias mombin and Ficus exasperata. Toxicol Rep. 2015;2:261-7. https://doi.org/10.1016/j.toxrep.2015.01.002 PMid:28962358
Ramachandran S, Nandhakumar S, Raju D. Development and evaluation of biodegradable chitosan microspheres loaded with ranitidine and cross linked with glutaraldehyde. Int J PharmTech Res. 2011;3:488-96. https://doi.org/10.3923/ajdd.2011.105.120
Rahim NA, Hassandarvish P, Golbabapour S, Ismail S, Tayyab S, Abdulla MA. Gastroprotective effect of ethanolic extract of Curcuma xanthorrhiza Leaf against ethanol-induced gastric mucosal lesions in Sprague-Dawley rats. Biomed Res Int. 2014;2014:416409.
Nabilah N, Ezzuddin N, Salwa S, Gani A, Zaidan UH, Halmi E, et al. Antioxidant activities of Phaleria macrocarpa fruits. Pal Archs J Achaeol Egypt Egyptol. 2020;17:1029-38.
Maleki SJ, Crespo JF, Cabanillas B. Anti-inflammatory effects of flavonoids. Food Chem. 2019;299:125124.
Serafim C, Araruna ME, Júnior EA, Diniz M, Hiruma-Lima C, Batista L. A review of the role of flavonoids in peptic ulcer (2010-2020). Molecules. 2020;25:5431. https://doi.org/10.3390/molecules25225431 PMid:33233494
De Lira Mota KS, Dias GE, Pinto ME, Luiz-Ferreira Â, Souza- Brito AR, Hiruma-Lima CA, et al. Flavonoids with gastroprotective activity. Molecules. 2009;14:979-1012. https://doi.org/10.3390/molecules14030979 PMid:19305355
Daure E, Ross L, Webster CR. Gastroduodenal ulceration in small animals: Part 2. Proton pump inhibitors and histamine-2 receptor antagonists. J Am Anim Hosp Assoc. 2017;53(1):11-23. https://doi.org/10.5326/JAAHA-MS-6634 PMid:27841679
Kavitt RT, Lipowska AM, Anyane-Yeboa A, Gralnek IM. Diagnosis and treatment of peptic ulcer disease. Am J Med. 2019;132():447-56. https://doi.org/10.1016/j.amjmed.2018.12.009 PMid:30611829
Savarino E, Zentilin P, Marabotto E, Bodini G, Coletta MD, et al. A review of pharmacotherapy for treating gastroesophageal reflux disease (GERD). Expert Opin Pharmacother. 2017;18(13):1333-43. https://doi.org/10.1080/14656566.2017.1361407 PMid:28754071
Zheng HM, Choi MJ, 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(1):38-46. https://doi.org/10.1089/jmf.2015.3464 PMid:26469560
Ichikawa T, Ishihara K. Protective effects of gastric mucus. In: Gastritis and Gastric Cancer New Insights in Gastroprotection, Diagnosis and Treatments. Norderstedt: BoD-Books on Demand; 2011.
Araki H, Ukawa H, Sugawa Y, Yagi K, Suzuki K, Takeuchi K. The roles of prostaglandin E receptor subtypes in the cytoprotective action of prostaglandin E2 in rat stomach. Aliment Pharmacol Ther Suppl. 2000;1(Suppl 1):116-24. https://doi.org/10.1046/j.1365-2036.2000.014s1116.x PMid:10807413
LaCasa C, Villegas I, De La Lastra CA, Motilva V, Calero MJ. Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol. 2000;71(1-2):45-53. https://doi.org/10.1016/s0378-8741(99)00174-9 PMid:10904145
Ross JA, Kasum CM. Dietary flavonoids: Bioavailability, metabolic effects, and safety. Ann Rev Nutr. 2002;22:19-34. https://doi.org/10.1146/annurev.nutr.22.111401.144957 PMid:12055336
Zayachkivska OS, Konturek SJ, Drozdowicz D, Konturek PC, Brzozowski T, Ghegotsky MR. Gastroprotective effects of flavonoids in plant extracts. J Physiol Pharmacol. 2005;56(Suppl 1):219-31. PMid:15800396
Downloads
Published
How to Cite
License
Copyright (c) 2022 Dadang Irfan Husori, Marianne Marianne, Nabila Deli Syafarina Lubis, Kurnia Lavinda Yusfa, Intan Farah Diba Angela (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)
