Chemical, biological, and pharmacological evaluation of the aqueous extract of Ilex paraguariensis, St. Hill. (Aquifoliaceae)
DOI:
https://doi.org/10.33448/rsd-v11i2.25335Keywords:
Yerba mate; Gastroprotection; Phenolics; Biochemical markers; Antimicrobial; Antioxidants.Abstract
This study aimed to quantify the total phenolic and flavonoid contents in the aqueous extract of Ilex paraguariensis (EIP) and investigate its antioxidant, antimicrobial, antiulcerogenic, and antidepressant properties with concomitant verification of its effects on relevant biochemical parameters using in vivo models. EIP has in its composition 236.28 ± 11.83 mg GAE/g of total phenolics and 44.07 ± 5.56 mg QE/g of total flavonoids, corroborating its antioxidant activity. Antimicrobial assays against gram-positive (Staphylococcus aureus and Enterococcus faecalis) and gram-negative bacteria (Escherichia coli e Pseudomonas aeruginosa) showed a promising activity of EIP. The EIP administered at 500 and 1000 mg/kg doses prevented the development of gastric ulcers induced in rats following immobilization at 4 °C, however, in the ethanol-induced ulcers no significant effects were observed up to a dose of 1000 mg/kg. Gastric secretion and total acidity index in pylorus-ligated rats were reduced after treatment with EIP, and the pH did not change significantly compared to the control in the tested model. Administration of EIP to mice (250, 500, and 1000 mg/kg) significantly altered the barbiturate-induced sleep time and results of the tail suspension and forced swim test. Repeated doses of EIP did not significantly alter the evaluated biochemical markers (blood glucose, urea, creatinine, triglycerides, and total cholesterol). The results indicate that EIP may relieve gastrointestinal disorders by reducing acid secretion and decreasing immobility time in mice, suggesting an antidepressant effect. Notably, administration of multiple doses of EIP was considered preliminarily safe.
References
Abbasi-Maleki, S., Kadkhoda, Z., Taghizad-Farid, R. (2020). The antidepressant-like effects of Origanum majorana essential oil on mice through monoaminergic modulation using the forced swimming test. Journal of Traditional and Complementary Medicine, 10 (4), 327-335.
Aguwa, C., Lawal A. (1988). Pharmacologic studies on the active principles of Calliandra portoricensis leaf extracts. Journal of Ethnopharmacology, 22(1), 63–71.
Akıncı, A., Esrefoglu, M., Taşlıdere, E., Ateş, B. (2017). Petroselinum Crispum is effective in reducing stress-induced gastric oxidative damage. Balkan Megdical Journal, 34(1), 53-59.
Anesini, C., Turner, S., Cogoi, L., Filip, R. (2012). Study of the participation of caffeine and polyphenols on the overall antioxidant activity of mate (Ilex paraguariensis). LWT – Food Science and Technology, 45(2), 299-304.
Arakchaa, K.D., Salchak, S.M., Razuvaeva, Y.G., Toropova, A.A., Smirnova, I.N., Nikolaev, S.M., Merzlikin, A.V., Ponomarenko, G.N. (2019). The gastroprotective action of acidic mineral water from the Azhyg-Sug source on the stress-induced injuries to the stomach of white rats. Voprosy Kurortologii, Fizioterapii, i Lechebnoi Fizicheskoi Kultury, 96(2), 54-60.
Ash, A.S.F., Schild, H.O. (1966). Receptors mediating some actions of histamine. British Journal of Pharmacology and Chemotherapy, 27(2), 427–439.
Baggio, C.H., Freitas, C.S., Nhaducue, P.F., Rieck, L., Marques, M.C.A. (2002). Action of crude aqueous extract of leaves of Achillea millefolium L. (Compositae) on gastrointestinal tract. Revista Brasileira de Farmacognosia, 12(1), 31-33.
Basile, A., Sorbo, S., Giordano, S., Ricciardi, L., Ferrara, S., Montesano, D., Cobianchi, R.C., Vuotto, M.L., Ferrara, L. (2000). Antibacterial and allelopathic activity of extract from Castanea sativa leaves. Fitoterapia, 71, 110-116.
Bastos, D.H.M., Saldanha, L.A., Catharino, R.R., Sawaya, A., Cunha, I.B., Carvalho, P.O., Eberlin, M.N. (2007). Phenolic antioxidants identified by ESI-MS from Yerba-mate (Ilex paraguariensis) and green tea (Camelia sinensis) extracts. Molecules, 12(3), 423-432.
Berté, K.A.S., Beux, M.R., Spada, P.K. W. D. S., Salvador, M., Hoffmann-Ribani, R. (2011). Chemical composition and antioxidant activity of yerba-mate (Ilex paraguariensis A.St.-Hill., Aquifoliaceae) extract as obtained by spray drying. Journal of Agricultural and Food Chemistry, 59(10), 5523-5527.
Beyer, R.E. (1994). The role of ascorbate in antioxidant protection of biomembranes: interaction with vitamin E and coenzyme Q. Journal of Bioenergetics and Biomembranes, 26(4), 349-358.
Birdane, F.M., Cemek, M., Birdane, Y.O., Gülçin, I., Büyukokuroglu, M.E. (2007). Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats. World Journal of Gastroenterology, 13(4), 607-611.
Bisognin, D.A., da Luz, L.V., Lencina, K.H., Santos, C.O., Sautter, C.K. (2019). Contents of total phenolics and flavonoids in and antioxidant activity of Ilex paraguariensis leaves. Pesquisa Agropecuaria Brasileira 54, 1-8.
Bojic, M., Haas, V.S., ŀaric, D., Malel, Ž. (2013). Determination of flavonoids, phenolic ccids, and xanthines in mate tea (Ilex paraguariensis St.-Hill.). Journal of Analytical Methods in Chemistry, 2013, 1-6.
Borrelli, F., Izzo, A.A. (2000). The plant kingdom as a source of anti-ulcer remedies. Phytotherapy Research, 14, 581-591.
Brunton, L.L. (1996). Fármacos para controle da acidez gástrica e tratamento de úlceras pépticas. In: Goodman & Gilman as bases farmacológicas da terapêutica, 9 ed. Rio de Janeiro: McGraw-Hill, 663-674.
Burris, K.P., Davidson, P.M., Stewart Jr, C.N., Harte, F.M. (2011). Antimicrobial activity of Yerba Mate (Ilex paraguariensis) aqueous extracts against Escherichia coli O157:H7 and Staphylococcus aureus. Journal of Food Science, 76(6), 456-462.
Campos, M.M., Fernandes, E.S., Ferreira, J., Bortolanza, L.B., Santos, A., Calixto, J.B. (2004). Pharmacological and neurochemical evidence for antidepressant-like effects of the herbal product catuama. Pharmacology Biochemistry and Behavior, 78, 757–764.
Carlini, E.A. (1973). Farmacologia pratica sem aparelhagem. Ed. Sarvier, São Paulo, Brazil.
Cascon, C.S. (1995). Amino acids in Ilex paraguariensis. Boletin del Instituto de Quimica Argentina, 38, 7–15.
Chan, F.K., Leung, W. (2002). Peptic-ulcer disease. The Lancet, 360, 933–941.
Clinical and Laboratory Standards Institute – CLSI (2012). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, sixth ed. NCCLS document, Pennsylvania, USA.
Cola-Miranda, M., Barbastefano, V., Hiruma-lima, C.A., Calvo, T.R., Vilegas, W., Brito, A.R.M.S. (2006). Antiulcerogenic activity of Indigofera truxillensis Kunth. Biota Neotropica, 6(3), 1-13.
Colpo, G., Trevisol, F., Teixeira, A.M., Fachinetto, R., Pereira, R.P., Athayde, M.L., Rocha, J.B.T., Burger, M.E. (2007). Ilex paraguariensis has antioxidant potential and attenuates haloperidol-induced orofacial dyskinesia and memory dysfunction in rats. Neurotoxicity Research, 12, 171-180.
Costa, D.E.M., Racanicci, A.M.C., Santana, A.P. (2017). Atividade antimicrobiana da erva-mate (Ilex paraguariensis) contra microrganismos isolados da carne de frango. Ciência Animal Brasileira, 18, 1–7.
de Andrade, F., de Albuquerque, C.A.C., Maraschin, M., da Silva, E.L. (2012). Safety assessment of yerba mate (Ilex paraguariensis) dried extract: Results of acute and 90 days subchronic toxicity studies in rats and rabbits. Food and Chemical Toxicology, 50, 328–334.
de Souza, L.M., Dartora, N., Scoparo, C.T., Cipriani, T.R., Gorin, P.A., Iacomini, M., Sassaki, G.L. (2011). Comprehensive analysis of maté (Ilex paraguariensis) compounds: Development of chemical strategies for matesaponin analysis by mass spectrometry. Journal of Chromatography A, 1218, 7307–7315.
Devequi-Nunes, D., Machado, B.A.S., Barreto, G.A., Silva, J.R., da Silva, D.F., da Rocha, J.L.C., Brandão, H.N., Borges, V.M., Umsza-Guez, M.A. (2018). Chemical characterization and biological activity of six different extracts of propolis through conventional methods and supercritical extraction. PLoS One, 13, 1-20.
Domer, F.R. (1971). Animal experiments in pharmacological analysis. Thomas, Illinois, USA.
Elshazly, S.M., Abd El Motteleb, D.M., Ibrahim, I.A.A.E. (2018). Hesperidin protects against stress induced gastric ulcer through regulation of peroxisome proliferator activator receptor gamma in diabetic rats. Chemico-Biological Interactions, 291, 153-161.
Ferreira, S.H., Barata, L.E.S. (1998). Medicamentos a partir de plantas medicinais no Brasil. Academia Brasileira de Ciências, Rio de Janeiro, Brazil.
Ferrera, T.S., Heldwein, A.B., Santos, C.O., Somavilla, J., Sautter, C.K. (2016). Substâncias fenólicas, flavonoides e capacidade antioxidante em erveiras sob diferentes coberturas do solo e sombreamento. Revista Brasileira de Plantas Medicinais, 18, 588 – 596.
Girolometto, G., Avancini, C.A.M., Carvalho, H.H.C., Wiest, J.M. (2009). Atividade antibacteriana de extratos de erva mate (Ilex paraguariensis A.St.-Hill.). Revista Brasileira de Plantas Medicinais, 11, 49 – 55.
Glavin, G.B., Szabo, S. (1992). Experimental gastric mucosal injury: laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies. The FASEB Journal, 6, 825– 831.
Gõni, M.A., Eglinton, T.I. (1996). Stable carbon isotopic analyses of lignin-derived CuO oxidation products by isotope ratio monitoring-gas chromatography-mass spectrometry (irm-GC-MS). Organic Geochemistry, 24, 601-615.
Gonzalez, A., Ferreira, F., Vazquez, A., Moyna, P., Alonsi Paz, E. (1993). Biological screening of Uruguayan medicinal plants. Journal of Ethnopharmacology, 39, 217-220.
Gonzalez, F.G., Di Stasi, L.C.D. (2002). Anti-ulcerogenic and analgesic activities of the leaves of Wilbrandia ebracteata in mice. Phytomedicine, 9, 125–134.
Gorzalczany, S., Filip, R., del Alonso, M.R., Miño, J., Ferraro, G.E., Acevedo, C. (2001). Choleretic effect and intestinal propulsion of ‘mate’ (Ilex paraguariensis) and its substitutes or adulterants. Journal of Ethnopharmacology, 75, 291–294.
Gosmann, G., Schenkell, E.P. (1989). A new saponin from mate, Ilex paraguariensis. Journal of natural Products, 52(6), 1367-1370.
Grujic, N., Lepojevic, Z., Srdjenovic, B., Vladic, J., Sudji, J. (2012).. Effects of different extraction methods and conditions on the phenolic composition of mate tea extracts. Molecules, 17, 2518-2528.
Gugliuci, A. (1996). Antioxidant effects of Ilex paraguariensis: induction of decreased oxidability of human LDL in vivo. Biochemical and Biophysical Research Communications, 224, 338-344.
Heck, C.I., De Mejia, E.G. (2007). Yerba mate tea (Ilex paraguariensis): A comprehensive review on chemistry, health implications, and technological considerations. Journal of food science, 72, 132-151.
Hersey, S.J., Sachs, G. (1995). Gastric acid secretion. Physiological Reviews, 75, 155–189.
Khan, A.W., Khan, A., Ahmed, T. (2016). Anticonvulsant, anxiolytic, and sedative activities of Verbena officinalis. Frontiers in Pharmacology, 7, 1-8.
Kidsley, A.K., Abraham, S., Bell, J.M., O'Dea, M., Laird, T.J., Jordan, D., Mitchell, P., McDevitt, C.A., Trott, D.J. (2018). Antimicrobial susceptibility of Escherichia coli and Salmonella spp. isolates from healthy pigs in Australia: Results of a pilot national Survey. Frontiers in Microbiology, 9, 1-11.
Kinoshita, M., Noto, T., Tamaki, H. (1995). Effect of a combination of ecabet sodium and cimetidine on experimentally induced gastric lesions and gastric mucosal resistance to ulcerogenic agents in rats. Biological & Pharmaceutical Bulletin, 18, 223–226.
Liang, N., Kitts, D. (2015). Role of chlorogenic acids in controlling oxidative and inflammatory stress conditions. Nutrients, 8(1), 16-26.
Lim, D.W., Kim, J.G., Han, T., Jung, S.K., Lim, E.Y., Han, D., Kim, Y.T. (2015). Analgesic effect of Ilex paraguariensis extract on postoperative and neuropathic pain in rats. Biological and Pharmaceutical Bulletin, 38, 1573-1579.
Liu, L., Dong, Y., Shan, X., Li, L., Xia, B., Wang, H. (2019). Anti-depressive effectiveness of baicalin in vitro and in vivo. Molecules, 24, 1-8.
Ludka, F.K., Tandler, L.F., Kuminek, G., Olescowicz, G., Jacobsen, J., Simone, M. (2016). Ilex paraguariensis hydroalcoholic extract exerts antidepressant-like and neuroprotective effects: involvement of the NMDA receptor and the L-arginine-NO pathway. Behavioural Pharacology, 27(4), 484-392.
Martin, J.G.P., Porto, E., Alencar, S.M., Glória, E.M., Corrêa, C.B., Cabral, I.S.R. (2013). Antimicrobial activity of yerba mate (Ilex paraguariensis St. Hill.) against food pathogens. Revista Argentina de Microbiologia, 45, 93-98.
Meinhart, A.D., Bizzotto, C.S., Ballus, C.A., Rybka, A.C.P., Sobrinho, M.R., Cerro-Quintana, R.S., Teixeira-Filho, J., Godoy, H.T. (2010). Methylxanthines and phenolics content extracted during the consumption of mate Ilex paraguariensis St. Hill.) beverages. Journal of Agricultural and Food Chemistry, 58, 2188–2193.
Mendonça, M.A.A., Ribeiro, A.R.S., Lima, A.K. (2020). Red propolis and its dyslipidemic regulator formononetin: Evaluation of antioxidant activity and gastroprotective effects in rat model of gastric ulcer. Nutrients, 12, 1-13.
Mensor, L.L., Menezes, F.S., Leitão, G.G., Reis, A.S., dos Santos, T.C., Coube, C.S., Leitão, S.G. (2001). Screening of brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytotherapy Research, 15, 127–130.
Milioli, E.M., Cologni, P., Santos, C.C., Marcos, T.D., Yunes, V.M., Fernandes, M.S., Schoenfelder, T., Costa-Campos, L. (2007). Effect of acute administration of hydroalcohol extract of Ilex paraguariensis St. Hill. (Aquifoliaceae) in animal models of parkinson’s disease. Phytotherapy Research, 21, 771–776.
Mulholland, M.W., Debas, H.T. (1987). Recent advances in the treatment of duodenal ulcer disease. A surgical perspective. The Western Journal of Medicine, 147, 301–308.
Nakamura, T., Silva, F.S., da Silva, D.X., de Souza, M.W., Moya, H.D. (2013). Determinação da atividade antioxidante e do teor total de polifenol em amostras de chá de ervas comercializadas em sachets. ABCS Helath Science, 38, 8-16.
Nardi, G., de Carvalho, E., de Oliveira, S., Nardi, V., Gelinski, T., Bortoluzzi, M., Maraschin, M. (2016). Ilex paraguariensis promotes orofacial pain relief after formalin injection: Involvement of noradrenergic pathway. Pharmacognosy Research, 8, 31-37.
Nehlig, A., Daval, J.L., Debry, G. (1992). Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Research Reviews, 17, 139–170.
Nemeroff, C.B., Owens, M.J. (2002). Treatment of mood disorders. Nature Neuroscience, 5, 1068–1070.
Nielsen, D.M., Carey, G.J., Gold, L.H. (2004). Antidepressant-like activity of corticotropin-releasing factor type-1 receptor antagonists in mice. European Journal of Pharmacology, 499(1-2), 135–146.
Nimse, S.B., Pal, D. (2015). Free radicals, natural antioxidants, and their reaction mechanisms. Royal Society of Chemistry Advances, 5, 27986–28006.
Nowacki, L.C., Stechman-Neto, J., Schiefer, E.M., Santos, A.F., Stinghen, A.E.M., Sassaki, G.L., de Souza, L.M., Cristoff, K.E., Souza, W.M. (2021). Ilex paraguariensis extract as an alternative to pain medications. Acta Pharmaceutical, 71(3), 383-398.
Oates, P.J., Hakkinen, J.P. (1988). Studies on the mechanism of ethanol-induced gastric damage in rats. Gastroenterology, 94, 10–21.
Paré, W.P., Glavin, G.B. (1993). Animal models of stress in pharmacology. Techniques in the Behavioral and Neural Sciences, 10, 413–441.
Pehlivan, F.E. (2017). Vitamin C: An antioxidant agent. InTech, 1-13.
Porsolt, R.D., Bertin, A., Jalfre, M. (1977). Behavioral despair in mice: a primary screening test for antidepressants. Archives Internationales de Pharmacodynamie et de Therapie, 229(2), 327–336.
Prediger, R.D., Fernandes, S., Rial, D., Wopereis, S., Pereira, V.S., Bosse, T.S., Silva, C.B.D., Carradore, R.S., Machado, M.S., Cechinel-Filho, V., Costa-Campos, L. (2008). Effects of acute administration of the hydroalcoholic extract of mate tea leaves (Ilex paraguariensis) in animal models of learning and memory. Journal of Ethnopharmacology, 120, 465–473.
Pressi, C., Wietholter, P., Flores, R.A. (2021). Antibacterial and antifungal action of yerba mate extract and evaluation of toxicity in Artemia salina. Brazilian Applied Science Review, 5, 241-256.
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, 337-41.
Ramirez-Mares, M.V., Chandra, S., de Mejia, E.G. (2004). In vitro chemopreventive activity of Camellia sinensis, Ilex paraguariensis and Ardisia compressa tea extracts and selected polyphenols. Mutation Research, 554(1-2), 53–65.
Reginatto, F., Athayde, M., Gosmann, G., Schenkel, E. (1999). Methylxanthines accumulation in Ilex species - caffeine and theobromine in erva-mate (Ilex paraguariensis) and other ilex species. Journal of the Brazilian Chemical Society, 10(6), 443-446.
Reis, E.M., Schreiner Neto, F.W., Cattani, V.B., Peroza, L.R., Busanello, A., Leal, C.Q., Boligon, A.A., Lehmen, T.F., Libardoni M., Athayde, A.L., Fachinetto, R. (2014). Antidepressant-like effect of Ilex paraguariensis in Rats. Biomed Research International, 2014, 1-9.
Ricco, R.A., Wagner, M.L., Gurni, A.A. (1991). Estudio comparative de flavonoids en seis especies austrosudamericanas del gênero Ilex. Acta Farmaceutica Bonaerense, 10, 29-35.
Robert, A., Nezamis, J.E., Lancaster, C., Hanchar, A.J. (1979). Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology, 77, 433–443.
Sairam, K., Rao, C., Babu, M., Kumar, K., Agrawal, V., Goel, R.K. (2002). Antiulcerogenic effect of methanolic extract of Emblica officinalis: an experimental study. Journal of Ethnopharmacology, 82, 1–9.
Schechter, L.E., Ring, R.H., Beyer, C.E., Hughes, Z.A., Khawaja, X., Malberg, J.E., Rosenzweig-Lipson, S. (2005). Innovative approaches for the development of antidepressant drugs: current and future strategies. The Journal of American Society for Experimental Neuro Therapeutics, 2, 590-611.
Schinella, G., Troiani, G., Dávila, V., de Buschiazzo, P., Tournier, H. (2000). Antioxidant effects of an aqueous extract of Ilex paraguariensis. Biochemical and Biophysical Research Communications, 269, 357–360.
Senay, E.C., Levine, R.J. (1967). Synergism between gold and restraint for rapid production of stress ulcers in rats. Experimental Biology and Medicine, 124, 1221–1223.
Shay, H., Komarov, S., Fels, S., Meranze, D., Gruenstein, M., Siplet, H. (1945). A simple method for the uniform production of gastric ulceration in the rat. Gastroenterology, 5, 43–61.
Silva, P. (2010). Farmacologia. Guanabara koogan, Rio de Janeiro, Brazil.
Sousa, F., Melo, C., Monteiro, A., Lima, V., Gutierrez, S., Pereira, B., Barbosa-Filho, J., Vasconcelos, S., Fonteles, M., Viana, G. (2004). Antianxiety and antidepressant effects of riparin III from Aniba riparia (nees) Mez (Lauraceae) in mice. Pharmacology Biochemistry and Behavior, 78(1), 27– 33.
Stein, F.L.P., Schmidt, B., Furlong, E.B., Soares, L.A.S., Soares, M.C.F., Vaz, M.R.C., Baisch, A.L.M. (2005). Vascular responses to extractable fractions of ilex paraguariensis in rats fed standard and high-cholesterol diets. Biological Research For Nursing, 7(2), 146–156.
Steru, L., Chermat, R., Thierry, B., Simon, P. (1985). The tail suspension test: A new method for screening antidepressants in mice. Psychopharmacology, 85, 367–370.
Szabo, S., Nagy, L., Plebani, M. (1992). Glutathione, protein sulfhydryls and cysteine proteases in gastric mucosal injury and protection. Clinica Chimica Acta, 206(1-2), 95–105.
Takeuchi, Y., Matsushita, H., Kawano, H., Sakai, H., Yoshimoto, K., Sawada, T. (1999). TRH increases cerebrospinal fluid concentration of kynurenine. NeuroReport, 10(17), 3601–3603.
Tam, V.H., Kabbara, S., Vo, G., Schilling, A.N., Coyle, E.A. (2006). Comparative pharmacodynamics of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy, 50(8), 2026-2031.
Valduga, A.T., Gonçalves, I.L., Borges, A.C.P., Mielniczki-Pereira, A.A., Picolo, A.P. (2016). Cytotoxic/antioxidante activity and sensorial acceptance of yerbamate development by oxidation process. Acta Scientiarum, 38(1), 115 – 121.
Villela, G.G. (1938). Determination of vitamin B1 in yerba mate´ by the Schopfer-Jung method. Comptes Rendus des Seances de la Societe´ de Biologie et de ses Filiales, 129, 987–989.
Woisky, R.G., Salatino, A. (1998). Analysis of propolis: Some parameters and procedures for chemical quality control. Journal of Apicultural Research, 37(2), 99–105.
Yankelevitch-yahav, R., Franko, M., Huly, A., Doron, R. (2015). The forced swim test as a model of depressive-like behavior. Journal of Visualized Experiments, 97, 1-13.
Zhang, C., Zhao, X., Mao, X., Liu, A., Liu, Z., Li, X., Bi, K., Jia, Y. (2014). Pharmacological evaluation of sedative and hypnotic effects of schizandrin through the modification of pentobarbital induced sleep behaviors in mice. European Journal of Pharmacology, 744, 157–163.
Zhou, D., Yang, Q., Tian, T., Chang, Y., LI, Y., Duan, L., Li, H., Wang, S. (2020). Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats: involvement of the nrf2/ho-1 signaling and anti-apoptosis role. Biomedicine & Pharmacotherapy, 126, 1-10.
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Copyright (c) 2022 Andressa Flores Santos; Elberth Manfron Schiefer; Mônica Surek; Cleverson Antônio Ferreira Martins; Paulo Roberto Worfel; Guilherme Lanzi Sassaki; Lauro Mera de Souza; Luciana Cristina Nowacki; Wesley Mauricio de Souza
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