Antioxidant and gastroprotective effects of the ethyl acetate extract from Stemodia maritima L. in ethanol-induced gastric ulcer model

Authors

DOI:

https://doi.org/10.33448/rsd-v10i15.22548

Keywords:

Antiulcer; Phenolic compounds; Cytotoxicity; Oxidative stress.

Abstract

Stemodia maritima L., is a shrub of the Plantaginaceae family, with some biological activities already described, such as: larvicide, antimicrobial, and anti-inflammatory. Thus, the objective of this work was to evaluate the antioxidant, and gastroprotective activities of the ethyl acetate extract from S. maritima. The phytochemical profile was investigated through the quantification of total phenolic compounds, flavonoids, and CCD analysis. The toxicity of the extract was performed through cell viability using L929 line cell, and acute toxicity by the OECD Guide 423. The antioxidant activity was analyzed by the methods of reduction of the ferric ion (FRAP), total antioxidant activity (TAA), and the gastroprotective activity by the absolute ethanol-induced gastric ulcer model, with analysis of NO, MDA, GSH and MPO levels in the stomach tissues. In the phytochemical profile it was possible to identify the presence of flavonoids, triterpenes, steroids, mono, and sesquiterpenes. The extract was not cytotoxic against L929 lineage, maintaining cell viability above 70% at the doses tested, and in acute toxicity it did not show physiological changes indicative of toxicity compared to the control group. The extract presented antioxidant activity of 157.3 ± 9.7 mg equivalent of Trolox/g of extract in the FRAP method, and 50.0 ± 1.1 % by TAA. The ethyl acetate extract of S. maritima, at the doses tested, reduced the ulcerative lesion index compared to the injured control group, increased the levels of NO and GSH, and was able to decrease the concentrations of MDA and MPO, enhancing their gastroprotective activity.

Author Biography

Rayane Siqueira de Sousa, Federal University of Pernambuco

Aluna de doutorado

References

Abud, M. A., Molina, A., Wenedel, G., Juan Hikawczuk, V. E., Pelzer, L. E., & Maria, A. O. (2012). Gastroprotective effects of Plantago major and metabolites in rats. Latin American Journal of Pharmacy, 31(8), 1203-6.

Ali, S. S., Ahsan, H., Zia, M. K., Siddiqui, T., & Khan, F. H. (2020). Understanding oxidants and antioxidants: Classical team with new players. Journal of food biochemistry, 44(3), e13145. https://doi.org/10.1111/jfbc.13145

Antonisamy, P., Subash-Babu, P., Albert-Baskar, A., Alshatwi, A. A., Aravinthan, A., Ignacimuthu, S., Choi, K. C., Lee, S. C., & Kim, J. H. (2016). Experimental study on gastroprotective efficacy and mechanisms of luteolin-7-O-glucoside isolated from Ophiorrhiza mungos Linn. in different experimental models. Journal of functional foods, 25, 302-313. https://doi.org/10.1016/j.jff.2016.06.003

Ateufack, G., Mokam, E. C. D., Mbiantcha, M., Feudjio, R. B. D., David, N., & Kamanyi, A. (2015). Gastroprotective and ulcer healing effects of Piptadeniastrum africanum on experimentally induced gastric ulcers in rats. BMC complementary and alternative medicine, 15(1), 1-10. https://doi.org/10.1186/s12906-015-0713-5

Benzie, I. F. F., & Strain, J. J. (1996). The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Analytical Biochemistry, 239(1), 70-76. https://doi.org/10.1006/abio.1996.0292

Beserra, A. M. S., Calegari, P. I., Souza, M. C., Santos, R. A. N., Lima, J. C., Silva, R. M., Balogun, S. O., & Martins, D. T. (2011). Gastroprotective and ulcer-healing mechanisms of ellagic acid in experimental rats. Journal of Agricultural and Food Chemistry, 59(13), 6957-6965. https://doi.org/10.1021/jf2003267

Bradley, P. P., Priebat, D. A., Christensen, R. D., & Rothstein, G. (1982). Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. Journal of Investigative Dermatology, 78(3), 206-209. https://doi.org/10.1111/1523-1747.ep12506462

Chen, B. L., Wang, Y. J., Guo, H., & Zeng, G. Y. (2016). Design, synthesis, and biological evaluation of crenatoside analogues as novel influenza neuraminidase inhibitors. European Journal of Medicinal Chemistry, 109, 199-205. https://doi.org/10.1016/j.ejmech.2015.12.031

Chinedu, O., & Ibrahim, G. K. (2017). International Journal of Current Research and Academic Review. Int. J. Curr. Res. Aca. Rev, 5(6), 113-118. https://doi.org/10.20546/ijcrar.2017.506.016

Choudhary, M. K., Bodakhe, S. H., & Gupta, S. K. (2013). Assessment of the antiulcer potential of Moringa oleifera root-bark extract in rats. Journal of acupuncture and meridian studies, 6(4), 214-220. https://doi.org/10.1016/j.jams.2013.07.003

Cook, D., & Guyatt, G. (2018). Prophylaxis against upper gastrointestinal bleeding in hospitalized patients. New England Journal of Medicine, 378(26), 2506-2516. https://doi.org/10.1056/NEJMra1605507

Czekaj, R., Majka, J., Magierowska, K., Sliwowski, Z., Magierowski, M., Pajdo, R., Ptak-Belowska, A., Surmiak, M., Kwiecien, S., & Brzozowski, T. (2018). Mechanisms of curcumin-induced gastroprotection against ethanol-induced gastric mucosal lesions. Journal of gastroenterology, 53(5), 618-630. https://doi.org/10.1007/s00535-017-1385-3

Draper, H. H., & Hadley, M. (1990). Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol, 186, 31-421. https://doi.org/10.1016/0076-6879(90)86135-I

Dunkic, V., Kosalec, I., Joze Kosir, I., Potocnik, T., Cerenak, A., Zovko Koncic, M., Dubravka, V., Dragojevic Muller, I., Kopricanec, M., Bezic, N., Srecec, S., & Kremer, D. (2015). Antioxidant and antimicrobial properties of Veronica spicata L.(Plantaginaceae). Current drug targets, 16(14), 1660-1670.

Farrag, A. R. H., Abdallah, H. M. I., Khattab, A. R., Elshamy, A. I., Gendy, A. E. N. G. E., Mohamed, T. A., & Hegazy, M. E. F. (2019). Antiulcer activity of Cyperus alternifolius in relation to its UPLC-MS metabolite fingerprint: a mechanistic study. Phytomedicine, 62, 152970. https://doi.org/10.1016/j.phymed.2019.152970

Green, L. C., Tannembaun, S. R., & Goldman, P. (1981). Nitrate synthesis in the germfree and conventional rat. Science, 212(4490), 56-58. https://doi.org/10.1126/science.6451927

Gulcin, İ. (2020). Antioxidants and antioxidant methods: An updated overview. Archives of toxicology, 94(3), 651-715. https://doi.org/10.1007/s00204-020-02689-3

Hampshire, V. A., & Gilbert, S. H. (2019). Refinement, reduction, and replacement (3R) strategies in preclinical testing of medical devices. Toxicologic pathology, 47(3), 329-338. https://doi.org/10.1177/0192623318797289

Harput, U. S., Genc, Y., & Saracoglu, I. (2012). Cytotoxic and antioxidative activities of Plantago lagopus L. and characterization of its bioactive compounds. Food and chemical toxicology, 50(5), 1554-1559. https://doi.org/10.1016/j.fct.2012.01.019

Kavitt, R. T., Lipowska, A. M., Anyane-Yeboa, A., & Gralnek, I. M. (2019). Diagnosis and treatment of peptic ulcer disease. The American journal of medicine, 132(4), 447-456. https://doi.org/10.1016/j.amjmed.2018.12.009

Lanas, A., & Chan, K. L. (2017). Peptic ulcer disease. Lancet, 390(10094), 613-624. https://doi.org/10.1016/S0140-6736(16)32404-7

Li, H. B., Wong, C. C., Cheng, K. W., & Chen, F. (2008). Antioxidant properties in vitro and total phenolic contents in methanol extracts from medicinal plants. LWT - Food Science and Technology, 41(3), 385-390. https://doi.org/10.1016/j.lwt.2007.03.011

Li, W., Zhou, J., & Xu, Y. (2015) Study of the in vitro cytotoxicity testing of medical devices. Biomedical Reports, 3(5), 617–620. https://doi.org/10.3892/br.2015.481

Liu, Z., Liu, Y., Pu, Z., Wang, J., Zheng, Y., Li, Y., & Wei, Y. (2013). Regulation, evolution, and functionality of flavonoids in cereal crops. Biotechnology letters, 35(11), 1765-1780. https://doi.org/10.1007/s10529-013-1277-4

Moreira, H. J. C.; & BRAGANÇA, H. B. N. (2011). Manual de identificação de plantas infestantes: Hortifrúti. São Paulo: FMC Agricultural Products.

Morimoto, Y., Shimohara, K., Oshima, S., & Sukamoto, T. (1991). Effects of the new antiulcer agent KB-5492 on experimental gastric mucosal lesions and gastric mucosal defensive factors, as compared to those of teprenone and cimetidine. The Japanese Journal of Pharmacology, 57(4), 495-505. https://doi.org/10.1254/jjp.57.495

Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal Immunological Methods, 65(1-2), 55-63. https://doi.org/10.1016/0022-1759(83)90303-4

Nicolau, L. A., Carvalho, N. S., Pacífico, D. M., Lucetti, L. T., Aragão, K. S., Véras, L. M., Souza, M. H., Leite, J. R., & Medeiros, J. V. R. (2017). Epiisopiloturine hydrochloride, an imidazole alkaloid isolated from Pilocarpus microphyllus leaves, protects against naproxen-induced gastrointestinal damage in rats. Biomedicine & Pharmacotherapy, 87, 188-195. https://doi.org/10.1016/j.biopha.2016.12.101

OECD. Organization for Economic Cooperation and Development (2001). Acute oral toxicity - acute toxic class method. Guidelines for the testing of chemicals, OECD 423, Section 4, OECD Publishing, Paris.

Pekal, A., & Pyrzynska, K. (2014). Evaluation of aluminium complexation reaction for flavonoid content assay. Food Analytical Methods, 7(9), 1776-1782. https://doi.org/10.1007/s12161-014-9814-x

Prieto, P., Pineda, M., & Aguilar, M. (1999). Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Analytical Biochemistry, 269(2): 337-341. https://doi.org/10.1006/abio.1999.4019

Rodrigues, F. E., Lima, J. Q., Oliveira, M. D. C. F. D., Vasconcelos, J. N., Santiago, G. M., Mafezoli, J., Braz-Filho, R., & Arriaga, A. (2010). Diterpene and other constituents from Stemodia maritima (Scrophulariaceae). Journal of the Brazilian Chemical Society, 21(8), 1581-1586.

Russell, F. A., Mulabagal, V., Thompson, D. R., Singh-Wilmot, M. A., Reynolds, W. F., Nair, M. G., Langer, V., & Reese, P. B. (2011). Stemodin-derived analogues with lipid peroxidation, cyclooxygenase enzymes and human tumour cell proliferation inhibitory activities. Phytochemistry, 72(18), 2361-2368. https://doi.org/10.1016/j.phytochem.2011.08.024

Safavi, M., Shams-Ardakani, M., & Foroumadi, A. (2015). Medicinal plants in the treatment of Helicobacter pylori infections. Pharmaceutical biology, 53(7), 939-960. https://doi.org/10.3109/13880209.2014.952837

Sánchez-Mendoza, M. E., López-Lorenzo, Y., Cruz-Antonio, L., Matus-Meza, A. S., Sánchez-Mendoza, Y., & Arrieta, J. (2019). Gastroprotection of calein d against ethanol-induced gastric lesions in mice: role of prostaglandins, nitric oxide and sulfhydryls. Molecules, 24(3), 622. https://doi.org/10.3390/molecules24030622

Sangeetha, M. K., Vallabi, D. E., Sali, V. K., Thanka, J., & Vasanthi, H. R. (2013). Sub-acute toxicity profile of a modified resveratrol supplement. Food and chemical toxicology, 59, 492-500. https://doi.org/10.1016/j.fct.2013.06.037

Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman ́s reagent. Analytical Biochemistry, 25, 192-205. https://doi.org/10.1016/0003-2697(68)90092-4

Silva, F. R., Rodrigues, F. E., Gomes, A. R., Arriaga, A., Mafezoli, J., Lemos, T. L., Almeida, M. C., Santiago, G. P., Braz-Filho, R., Costa, J. G., Rodrigues, F. F. G., & Coutinho, H. D. (2014). Phytochemical study, antioxidant and antibacterial activities of Stemodia maritima. Química Nova, 37(9), 1474-1478. https://doi.org/10.5935/0100-4042.20140255

Simões, S., Lopes, R., Campos, M. C. D., Marruz, M. J., da Cruz, M. E. M., & Corvo, L. (2019). Animal models of acute gastric mucosal injury: Macroscopic and microscopic evaluation. Animal models and experimental medicine, 2(2), 121-126. https://doi.org/10.1002/ame2.12060

Song, S. H., Kim, J. E., Sung, J. E., Lee, H. A., Yun, W. B., Lee, Y. H., Song, H., & Hwang, D. (2019). Anti-ulcer effect of Gallarhois extract with anti-oxidant activity in an ICR model of ethanol/hydrochloride acid-induced gastric injury. Journal of traditional and complementary medicine, 9(4), 372-382. https://doi.org/10.1016/j.jtcme.2017.07.001

Sousa, R. S., Silva, J. A. G., Borba, E. F. O., Sousa, M. G. O., Silva, S. J. L., & da Silva, T. G. (2021). Análise fitoquímica e efeito gastroprotetor do extrato hexânico de Stemodia maritima L. Journal of Biology & Pharmacy and Agricultural Management, 17(2).

Teixeira, A. H., Freire, J. M., de Sousa, L. H., Parente, A. T., de Sousa, N. A., Arriaga, A., Silva, F. R., Melo, I. M., Silva, I. I., Pereira, K. M., Goes, P., Costa, J. J., Cristino Filho, G., Pinto, V. P., Chaves, H. V., & Bezerra, M. M. (2017). Stemodia maritima L. extract decreases inflammation, oxidative stress, and alveolar bone loss in an experimental periodontitis rat model. Frontiers in physiology, 8, 988. https://doi.org/10.3389/fphys.2017.00988

Vaghasiya, Y. K., Shukla, V. J., & Chanda, S. V. (2011). Acute oral toxicity study of Pluchea arguta boiss extract in mice. J Pharmacol Toxicol, 6(2), 113-23. https://doi.org/10.3923/jpt.2011.113.123

Zakaria, Z. A., Balan, T., Azemi, A. K., Omar, M. H., Mohtarrudin, N., Ahmad, Z., & Salleh, M. Z. (2016). Mechanism (s) of action underlying the gastroprotective effect of ethyl acetate fraction obtained from the crude methanolic leaves extract of Muntingia calabura. BMC complementary and alternative medicine, 16(1), 1-17. https://doi.org/10.1186/s12906-016-1041-0

Zhang, C., Gao, F., Gan, S., He, Y., Chen, Z., Liu, X., Fu, C., Qu, Y., & Zhang, J. (2019). Chemical characterization and gastroprotective effect of an isolated polysaccharide fraction from Bletilla striata against ethanol-induced acute gastric ulcer. Food and chemical toxicology, 131, 110539. https://doi.org/10.1016/j.fct.2019.05.047

Downloads

Published

24/11/2021

How to Cite

SOUSA, R. S. de .; SILVA, J. de A. G. .; BORBA, E. F. de O. .; RAMOS, K. R. de L. P. .; SILVA, C. J. A. da .; SILVA, P. A. da .; SILVA, M. G. de F. .; RAMOS, B. A. .; MENDES, R. F. V. .; SILVA, T. G. . Antioxidant and gastroprotective effects of the ethyl acetate extract from Stemodia maritima L. in ethanol-induced gastric ulcer model. Research, Society and Development, [S. l.], v. 10, n. 15, p. e195101522548, 2021. DOI: 10.33448/rsd-v10i15.22548. Disponível em: https://www.rsdjournal.org/index.php/rsd/article/view/22548. Acesso em: 28 apr. 2024.

Issue

Section

Health Sciences