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Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid

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Abstract

Ethanol is a psychoactive substance highly consumed around the world whose health problems include gastric lesions. Baccharis trimera is used in folk medicine for the treatment of gastrointestinal disorders. However, few studies have evaluated its biological and toxic effects. To validate the popular use of B. trimera and elucidate its possible antiulcerogenic and cytotoxic mechanisms, a hydroethanolic extract of B. trimera (HEBT) was evaluated in models of gastric lesions. Rats and mice were used to evaluate the protective and antiulcerogenic effects of HEBT on gastric lesions induced by ethanol, acetic acid, and chronic ethanol consumption. The effects of HEBT were also evaluated in a pylorus ligature model and on gastrointestinal motility. The LD50 of HEBT in mice was additionally estimated. HEBT was analyzed by nuclear magnetic resonance, and a high-performance liquid chromatography fingerprint analysis was performed. Oral HEBT administration significantly reduced the lesion area and the oxidative stress induced by acute and chronic ethanol consumption. However, HEBT did not protect against gastric wall mucus depletion and did not alter gastric secretory volume, pH, or total acidity in the pylorus ligature model. Histologically, HEBT accelerated the healing of chronic gastric ulcers in rats, reflected by contractions of the ulcer base. Flavonoids and caffeoylquinic acids were detected in HEBT, which likely contributed to the therapeutic efficacy of HEBT, preventing or reversing ethanol- and acetic acid-induced ulcers, respectively. HEBT antiulcerogenic activity may be partially attributable to the inhibition of free radical generation and subsequent prevention of lipid peroxidation. Our results indicate that HEBT has both gastroprotective and curative activity in animal models, with no toxicity.

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Abbreviations

NSAIDs:

Anti-inflammatory drugs

ROS:

Reactive oxygen species

B. trimera :

Baccharis trimera

HEBT :

Hydroethanolic extract of B. trimera

NMR:

Nuclear magnetic resonance

HPLC:

High-performance liquid chromatography

DPPH:

2,2-Diphenyl-1-picrylhydrazyl

WV:

Water + vehicle

EV:

Ethanol + vehicle

EHEBT:

Ethanol + HEBT

GSH:

Reduced glutathione

LOOH:

Lipid hydroperoxide

SOD:

Superoxide dismutase

GST:

Glutathione S-transferase

LD50 :

Median lethal dose

SEM:

Standard error of the mean

References

  • Abad MJ, Bermejo P (2007) Baccharis (Compositae): a review update. Arkivoc 7:76–96

    Google Scholar 

  • Aboy AL, Apel MA, Debenedetti S et al (2012) Assay of caffeoylquinic acids in Baccharis trimera by reversed-phase liquid chromatography. J Chromatogr A 1219:147–153. doi:10.1016/j.chroma.2011.11.042

    Article  CAS  PubMed  Google Scholar 

  • Almeida RN, Falcão ACGM, Diniz RST et al (1999) Metodologia para avaliação de plantas com atividade no sistema nervoso central e alguns dados experimentais. Rev Bras Farmacogn 80:72–76

    Google Scholar 

  • Anson ML (1938) The estimation of pepsin, trypsin, papain and catepsin with hemoglobin. J Gen Physiol 22:78–89

    Article  Google Scholar 

  • Baggio CH, De Martini Otofuji G, de Souza WM et al (2005) Gastroprotective mechanisms of indole alkaloids from Himatanthus lancifolius. Planta Med 71:733–738

    Article  CAS  PubMed  Google Scholar 

  • Biondo TM, Tanae MM, Coletta ED et al (2011) Antisecretory actions of Baccharis trimera (Less.) DC aqueous extract and isolated compounds: analysis of underlying mechanisms. J Ethnopharmacol 22:368–373. doi:10.1016/j.jep.2011.04.065

    Article  Google Scholar 

  • Birdane FM, Cemek M, Birdane YO et al (2007) Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats. World J Gastroenterol 13:607–611

    Article  PubMed  PubMed Central  Google Scholar 

  • Bonamin F, Moraes TM, Santos RC (2014) The effect of a minor constituent of essential oil from Citrus aurantium: the role of β-myrcene in preventing peptic ulcer disease. Chem Biol Interact 212:11–19. doi:10.1016/j.cbi.2014.01.009

    Article  CAS  PubMed  Google Scholar 

  • Burci LM, Pereira I, Silva LM et al (2013) Antiulcer and gastric antisecretory effects of dichloromethane fraction and piplartine obtained from fruits of Piper tuberculatum Jacq. in rats. J Ethnopharmacol 148:165–174. doi:10.1016/j.jep.2013.04.006

    Article  CAS  PubMed  Google Scholar 

  • Campos FR, Bressan J, Jasinski VC et al (2016) Baccharis (Asteraceae): chemical constituents and biological activities. Chem Biodivers 13:1–17. doi:10.1002/cbdv.201400363

    Article  Google Scholar 

  • Chai J (2011). Peptic ulcer disease. Available from http://www.intechopen.com/books/peptic-ulcer-disease.

  • Chen W, Weng YM, Tseng CY (2003) Antioxidative and antimutagenic activities of healthy herbal drinks from Chinese medicinal herbs. Am J Chin Med 31:523–532. doi:10.1142/S0192415X0300120X

    Article  PubMed  Google Scholar 

  • Chen FA, Wu AB, Chen CY (2004) The influence of treatments on the free radical scavenging activity of burdock and variations of its activity. Food Chem 86:479–484. doi:10.1016/j.foodchem.2003.09.020

    Article  CAS  Google Scholar 

  • Choi E, Hwang H, Kim I et al (2009) Protective effects of a polysaccharide from Hizikia fusiformis against ethanol toxicity in rats. Food Chem Toxicol 47:134–139. doi:10.1016/j.tiv.2009.08.031

    Article  CAS  PubMed  Google Scholar 

  • Corne SJ, Morrissey SM, Woods RJ (1974) Proceedings: a method for the quantitative estimation of gastric barrier mucus. J Physiol 242:116–117

    Google Scholar 

  • DeVault KR, Talley NJ (2009) Insights into the future of gastric acid suppression. Nat Rev Gastroenterol Hepatol 6:524–532. doi:10.1038/nrgastro

    Article  CAS  PubMed  Google Scholar 

  • Dias LFT, Melo ES, Hernandes LS et al (2009) Atividades antiúlcera e antioxidante Baccharis trimera (Less) DC (Asteraceae). Rev Bras Farmacogn 19:309–314. doi:10.1590/S0102-695X2009000200022

    Article  Google Scholar 

  • Eom CS, Park SM, Myung SK et al (2011) Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med 9:257–267. doi:10.1370/afm.1243

    Article  PubMed  PubMed Central  Google Scholar 

  • Franke A, Teyssen S, Singer MV (2005) Alcohol-related disease of the esophagus and stomach. Dig Dis 23:204–213. doi:10.1159/000090167

    Article  PubMed  Google Scholar 

  • Galuska B, Marazova K, Yankova T et al (2002) Effects of paracetamol and propacetamol on gastric mucosal damage and gastric lipid peroxidation caused acetylsalicylic acid (ASA) in rats. Pharmacol Res 46:141–148. doi:10.1016/S1043-6618(02)00083-X

    Article  Google Scholar 

  • Gao R, Yuan Z, Zhao Z et al (1998) Mechanism of pyrogallol autoxidation and determination of superoxide dimutase enzyme activity. Bioelectrochem Bioenerg 45:41–45

    Article  CAS  Google Scholar 

  • Garcia FAO, Tanae MM, Torres LMB et al (2014) A comparative study of two clerodane diterpenes from Baccharis trimera (Less.) DC on the influx and mobilization of intracellular calcium in rat cardiomyocytes. Phytomedicine 21:1021–1025. doi:10.1016/j.phymed.2014.04.018

    Article  CAS  PubMed  Google Scholar 

  • Gisbert J, Pajares M (2003) Helicobacter pylori infection and perforated peptic ulcer prevalence of infection and role of antimicrobial treatment. Helicobacter 8:159–167

    Article  PubMed  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  PubMed  Google Scholar 

  • Herz W, Pilotti AM, Soderholm AC et al (1977) New ent-clerodane-type diterpernoids from Baccharis trimera. J Org Chem 42:3913–3917

    Article  CAS  PubMed  Google Scholar 

  • Issac A, Gopakumar G, Kuttan R et al (2015) Safety and anti-ulcerogenic activity of a novel polyphenol-rich extract of clove buds (Syzygium aromaticum L). Food Funct 6:842–852. doi:10.1039/c4fo00711e

    Article  CAS  PubMed  Google Scholar 

  • Januário AH, Santos SL, Marcussi S et al (2004) Neo-clerodane diterpenoid, a new metalloprotease snake venom inhibitor from Baccharis trimera (Asteraceae): anti-proteolytic and anti-hemorrhagic properties. Chem Biol Interact 150:243–251

    Article  PubMed  Google Scholar 

  • Jiang ZY, Hunt JV, Wolff SP (1992) Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal Biochem 202:384–389

    Article  CAS  PubMed  Google Scholar 

  • Kangwan N, Park JM, Kim EH et al (2014) Quality of healing of gastric ulcers: natural products beyond acid suppression. World J Gastrointest Pathophysiol 15:40–47. doi:10.4291/wjgp.v5.i1.40

    Article  Google Scholar 

  • Lee BI, Nugroho A, Bachri MS et al (2010) Anti-ulcerogenic Effect and HPLC analysis of the caffeoylquinic acid-rich extract from Ligularia stenocephala. Biol Pharm Bull 33:493–497

    Article  CAS  PubMed  Google Scholar 

  • Lívero FAR, Stolf AM, Dreifuss AA et al (2014) The FXR agonista 6ECDCA reduces hepatic steatosis and oxidative stress induced by ethanol and low protein diet in mice. Chem Biol Interact 217:19–27. doi:10.1016/j.cbi.2014.03.014

    Article  PubMed  Google Scholar 

  • Losqui YR, Rozete FSS, Almeida MB et al (2009) Activity of Baccharis trimera (Less.) DC. Asteraceae on culture of retinal ganglion cells in vitro. Rev Bras Farmacogn 19:931–936. doi:10.1590/S0102-695X2009000600024

    Article  Google Scholar 

  • Mendonça NM, Silveira C, Oliveira JM et al (2013) Avaliação da atividade antiulcerogênica da Baccharis trimera (Less) DC em ratos. Saud Pesq 6:21–26. doi:10.17765/1983-1870.2013v6n1p%25p

    Google Scholar 

  • Moccelini SK, Silva VC, Ndiaye EA et al (2009) Estudo fitoquímico das cascas das raízes de Zanthoxylum rigidum Humb. & Bonpl. ex. Willd (Rutaceae). Quim Nov. 32:131–133. doi:10.1590/S0100-40422009000100025

  • Nogueira NPA, Reis PA, Laranja GAT et al (2011) In vitro and in vivo toxicological evaluation of extract and fractions from Baccharis trimera with anti-inflammatory activity. J Ethnopharmacol 138:513–522. doi:10.1016/j.jep.2011.09.051

    Article  CAS  PubMed  Google Scholar 

  • O’Malley P (2003) Gastric ulcers and GERD: the new “plagues” of the 21st century update for the clinical nurse specialist. Clin Nurse Specialist 17:286–289

    Article  Google Scholar 

  • Okabe S, Amagase K (2005) An overview of acetic acid ulcer models the history and state of the art of peptic ulcer research. Biol Pharm Bull 8:1321–1341

    Article  Google Scholar 

  • Okabe S, Roth JL, Pfeiffer CJ (1971) A method for experimental, penetrating gastric and duodenal ulcers in rats. Observations on normal healing. Am J Dig Dis 16:277–284

    Article  CAS  PubMed  Google Scholar 

  • Oliveira CB, Comunello LN, Lunardelli A et al (2012) Phenolic enriched extract of Bacchris trimera presents anti-inflammtory and antioxidant activities. Molecules 17:1113–1123. doi:10.3390/molecules17011113

    Article  PubMed  Google Scholar 

  • Pádua BC, Silva LD, Rossoni-Junior JV et al (2010) Antioxidant properties of Baccharis trimera in the neutrophils of Fischer rats. J Ethnopharmacol 129:381–386. doi:10.1016/j.jep.2010.04.018

    Article  Google Scholar 

  • Penston J, Wormsley KG (1987) Achlorhydria: hypergastrinaemia: carcinoids-a flawed hypothesis? Gut 28:488–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poynter D, Pick CR, Harcourt RA et al (1985) Association of long lasting unsurmountable histamine H2 blockade and gastric carcinoid tumours in the rat. Gut 26:1284–1295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rijke E, Out P, Niessen WMA et al (2006) Analytical separation and detection methods for flavonoids. J Chromatogr 1112:31–63

    Article  Google Scholar 

  • Robert A, Nezamis JE, Lancaster C et al (1979) Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology 77:433–443

    CAS  PubMed  Google Scholar 

  • Rocco A, Compare D, Angrisani D et al (2014) Alcoholic disease: liver and beyond. World J Gastroenterol 20:14652–14659. doi:10.3748/wjg.v20.i40.14652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  • Shay H, Komarov SA, Fels SS et al (1945) A simple method for the uniform production of gastric ulceration in the rat. Gastroenterology 5:43–61

    Google Scholar 

  • Sheen E, Triadafilopoulos G (2011) Adverse effects of long-term proton pump inhibitor therapy. Dig Dis Sci 56:931–950. doi:10.1007/s10620-010-1560-3

    Article  CAS  PubMed  Google Scholar 

  • Silva ARH, Reginato FZ, Guex CG et al (2016) Acute and sub-chronic (28 days) oral toxicity of tincture Baccharis trimera (Less) Backer in male and female rodent animals. Regul Toxicol Pharmacol 24:170–177. doi:10.1016/j.yrtph.2015.10.024

    Article  Google Scholar 

  • Simões-Pires CA, Queiroz EF, Henriques AT et al (2005) Isolation and on-line identification of anti-oxidant compounds from three Baccharis species by HPLC-UV-MS/MS with post-column derivatization. Phytochem Anal 16:307–314

    Article  PubMed  Google Scholar 

  • Singleton VL, Orthofer R, Lamuela-Raventos RM (1999) Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteus reagente. Methods Enzymol 299:152–178

    Article  CAS  Google Scholar 

  • Souza-Maria NCV, Tangerina MMP, Silva VC et al (2013) Abortive medicinal plants used by women of basic health units: ethnopharmacology and chromatographic analysis by TLC and HPLC. Rev Bras Pl Med 15:763–773. doi:10.1590/S1516-05722013000500018

    Article  Google Scholar 

  • Strapasson RLB, Rüdiger AL, Burrow RA et al (2015) A new sesquiterpene lactone and other constituents of Moquiniastrum polymorphum subsp. floccosum (Asteraceae). Nat Prod Comm 9:1541–1543

    Google Scholar 

  • Suchitra AD, Dkhar SA, Shewade DG et al (2003) Relative efficacy of some prokinetic drugs in morphine-induced gastrointestinal transit delay in mice. World J Gastroenterol 9:779–783. doi:10.3748/wjg.v9.i4.779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun J, Liang F, Bin Y, Li P, Duan C (2007) Screening non-colored phenolics in red wines using liquid chromatography/ultraviolet and mass spectrometry/mass spectrometry libraries. Molecules 12:679–693. doi:10.3390/12030679

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi K (2012) Pathogenesis of NSAID-induced gastric damage: importance of cyclooxygenase inhibition and gastric hypermotility. World J Gastroenterol 14:2147–2160. doi:10.3748/wjg.v18.i18.2147

    Article  Google Scholar 

  • Tarnawski A (2000) Molecular mechanisms of ulcer healing. Drug News Perspect 13:158–168. doi:10.12691/ajbr-4-1-4

    Article  CAS  PubMed  Google Scholar 

  • Verdi LG, Brighente MC, Pizzolatti MG (2005) Gênero Baccharis (Asteraceae): Aspectos químicos, econômicos e biológicos. Quim Nov. 28:85–94. doi:10.1590/S0100-40422005000100017

  • WHO - World Health Organization (2008) Is harmful use of alcohol a public health problem? Available from http://www.who.int/features/qa/66/en/index.html

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Acknowledgments

This research was supported by Fundação Araucária grants and scholarship of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/DS). We give thanks to Marília Locatelli Corrêa-Ferreira for helping in some phytochemical experiments.

Author contributions

FARL was responsible for every step of the experiments, data analysis, and manuscript preparation. LMS and DMF contributed with the in vivo experiments and manuscript writing. LFG and DGB contributed with the in vivo experiments. TBLP and ELBL contributed with Baccharis trimera’s production and extract preparation, while RLBS and MEAS performed the phytochemical analysis. MFPW, MEAS, and AA were responsible for data discussion and manuscript correction. AA was the senior researcher responsible for the project.

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Correspondence to Alexandra Acco.

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The authors declare no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The procedures performed in animals were in accordance with the ethical standards of the institution (UFPR).

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dos Reis Lívero, F.A., da Silva, L.M., Ferreira, D.M. et al. Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid. Naunyn-Schmiedeberg's Arch Pharmacol 389, 985–998 (2016). https://doi.org/10.1007/s00210-016-1262-2

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