Skip to main content
Log in

Pharmacological reports about gastroprotective effects of methanolic extract from leaves of Solidago chilensis (Brazilian arnica) and its components quercitrin and afzelin in rodents

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Solidago chilensis Meyenmost (Asteraceae), popularly known as “Brazilian arnica” or “arnica-do-campo,” is widely used in the folk medicine to treat gastric disorders. Based on this, the gastroprotective activity of S. chilensis methanolic extract was investigated. Besides, a phytochemical study allowed isolation of two flavonoids (quercitrin and afzelin). The gastroprotective effects were investigated in acute gastric ulcer models, and the antisecretory activity was assessed in vivo and in vitro. The adhered mucus levels, reduced glutathione (GSH) content and myeloperoxidase (MPO) activity were quantified in ulcerated tissues. The contribution of isolated compounds in extract effects was evaluated, and its doses were calculated according to its yield. To evaluate the in vivo healing properties of S. chilensis methanolic extract, a chronic gastric ulcer was induced in mice by 10 % acetic acid. Evaluation of tumor necrosis factor (TNF) levels was also performed at the site of the acetic acid-induced gastric ulcer. In parallel, effects on cell viability and cell proliferation of fibroblasts (L929 cells) were determined by in vitro trials. Firstly, the S. chilensis methanolic extract (100 or 300 mg/kg) reduced the ulcer area induced by ethanol/HCl in mice when compared to the vehicle group. Moreover, the S. chilensis extract (300 mg/kg) prevented the mucus depletion, the increase in MPO activity and the decrease in the GSH levels in the ulcerated gastric tissue. The S. chilensis extract also was able to decrease the indomethacin-induced gastric ulcer in rats at a dose of 100 mg/kg. The antisecretory effect of the extract (100 mg/kg, intraduodenal (i.d.)) was confirmed by the reduction in the volume and acidity in parallel to an increase in the pH of gastric content. In addition, quercitrin (1.38 mg/kg, but not 0.46 mg/kg) and afzelin (0.026 and 0.078 mg/kg) decreased the ethanol/HCl-induced gastric ulcer. In this model, quercitrin (1.38 mg/kg) prevented the depletion of gastric GSH content and both quercitrin (1.38 mg/kg) and afzelin (0.078 mg/kg) reduced the MPO activity. These compounds also inhibited the H+,K+-ATPase activity at a concentration of 1–100 μg/ml. In addition, the participation of quercitrin and afzelin in these effects also was confirmed. Furthermore, after 4 days of the treatment, an oral administration of S. chilensis methanolic extract (100 mg/kg) reduced the area of the gastric ulcer induced by acetic acid and the regeneration of the gastric mucosa was accompanied by a reduction in gastric TNF levels. The healing properties of the extract also were confirmed by enhancement of proliferation and coverage of scratched wounds in a fibroblast monolayer. Together, our results confirmed the gastroprotective effect of S. chilensis methanolic extract as well as its gastric healing potential and provided some support to the traditional use of S. chilensis for prevention and treatment of gastric lesions in complementation to its known anti-inflammatory properties.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • Abe Y, Inagaki K, Fujiwara A, Kuriyama K (2000) Wound healing acceleration of a novel transforming growth factor-β inducer, SEK-1005. Eur J Pharmacol 408:213–218

    Article  CAS  PubMed  Google Scholar 

  • Abreu Miranda M, Lemos M, Alves Cowart K, Rodenburg D, D McChesney J, Radwan MM, Furtado NA, Kenupp Bastos J (2015) Gastroprotective activity of the hydroethanolic extract and isolated compounds from the leaves of Solanum cernuum Vell. J Ethnopharmacol 172:421–429

    Article  CAS  PubMed  Google Scholar 

  • Allen A, Flemström G (2005) Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Physiol Cell Physiol 288:C1–C19

    Article  CAS  PubMed  Google Scholar 

  • Alonso J, Desmarchelier C (2006) Plantas medicinales autóctonas de la Argentina. Bases científicas para su aplicación en atención primaria de la salud. Lola, Buenos Aires, p 663

    Google Scholar 

  • Anson ML (1938) The estimation of pepsin, trypsin, papain, and cathepsin with hemoglobin. J Gen Physiol 22:79–89

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Apáti P, Houghton PJ, Kéry A (2004) HPLC investigation of antioxidant components in Solidago herba. Acta Pharm Hung 74:223–231

    PubMed  Google Scholar 

  • Balekar N, Katkam NG, Nakpheng T, Jehtae K, Srichana T (2012) Evaluation of the wound healing potential of Wedelia trilobata (L.) leaves. J J Ethnopharmacol 141:817–824

    Article  PubMed  Google Scholar 

  • Ballvé Alice C, de Siqueira NCS, Mentz LA, de Assis Brasil e Silva GA, José KFD (1995) Plantas medicinais de uso popular: atlas farmacognóstico. Ulbra, Canoas, p 205

    Google Scholar 

  • Berté PE, da Silva LJ, Comandulli NG, Rangel DW, Monache FD, Filho VC, Niero R, de Andrade SF (2014) Evaluation of the gastroprotective activity of the extracts, fractions, and pure compounds obtained from aerial parts of Rubus imperialis in different experimental models. Naunyn Schmiedebergs Arch Pharmacol 387:313–319

    Article  PubMed  Google Scholar 

  • Blois MS (1958) Antioxidant determinations by use of a stable free radical. Nature 181:1199–1200

    Article  CAS  Google Scholar 

  • Boltin D, Niv Y (2014) Pharmacological and alimentary alteration of the gastric barrier. Best Pract Res Clin Gastroenterol 28:981–994

    Article  CAS  PubMed  Google Scholar 

  • Boyce M, Dowen S, Turnbull G, van den Berg F, Zhao CM, Chen D, Black J (2014) Effect of netazepide, a gastrin/CCK(2) receptor antagonist, on gastric acid secretion and rabeprazole-induced hypergastrinaemia in healthy subjects. Br J Clin Pharmacol 79:744–755

    Article  Google Scholar 

  • Bradley PP, Priebat DA, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209

    Article  CAS  PubMed  Google Scholar 

  • Brzozowski T, Konturek PC, Sliwowski Z, Kwiecie S, Drozdowicz D, Pawlik M, Mach K, Konturek SJ, Pawlik WW (2006) Interaction of nonsteroidal anti-inflammatory drugs (NSAID) with Helicobacter pylori in the stomach of humans and experimental animals. J Physiol Pharmacol 57:67–79

    PubMed  Google Scholar 

  • Bucciarelli A, Minetti A, Milczakowskyg C, Skliar M (2010) Evaluation of gastroprotective activity and acute toxicity of Solidago chilensis Meyen (Asteraceae). Pharm Biol 48:1025–1030

    Article  PubMed  Google Scholar 

  • Chai J, Norng M, Tarnawski AS, Chow J (2007) A critical role of serum response factor in myofibroblast differentiation during experimental oesophageal ulcer healing in rats. Gut 56:621–630

    Article  CAS  PubMed  PubMed Central  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

    Article  CAS  Google Scholar 

  • Coqueiro A, Regasini LO, Skrzek SC, Queiroz MM, Silva DH, da Silva BV (2013) Free radical scavenging activity of Kielmeyera variabilis (Clusiaceae). Molecules 18:2376–2385

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  • Da Silva AG, Sousa CP, Koehler J, Fontana J, Christo AG, Guedes-Bruni RR (2010) Evaluation of an extract of Brazilian arnica (Solidago chilensis Meyen, Asteraceae) in treating lumbago. Phytother Res 24:283–287

    PubMed  Google Scholar 

  • Da Silva AG, Machado ER, de Almeida LM, Nunes RM, Giesbrecht PC, Costa RM, Costa HB, Romão W, Kuster RM (2015) A clinical trial with Brazilian arnica (Solidago chilensis Meyen) glycolic extract in the treatment of tendonitis of flexor and extensor tendons of wrist and hand. Phytother Res 29:864–869

    Article  PubMed  Google Scholar 

  • De Young LM, Kheifets JB, Ballaron SJ, Young JM (1989) Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents. Agents Actions 26:335–341

    Article  PubMed  Google Scholar 

  • Demircan B, Çelik G, Süleyman H, Akçay F (2005) Effects of indomethacin, celecoxib and meloxicam on glutathione, malondialdehyde and myeloperoxidase in rat gastric tissue. Pain Clinic 17:383–388

    Article  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphorus. J Biol Chem 66:375–400

    CAS  Google Scholar 

  • Fornai M, Natale G, Colucci R, Tuccori M, Carazzina G, Antonioli L, Baldi S, Lubrano V, Abramo A, Blandizzi C, Del Tacca M (2005) Mechanisms of protection by pantoprazole against NSAID-induced gastric mucosal damage. Naunyn Schmiedebergs Arch Pharmacol 372:79–87

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Goulart S, Moritz MI, Lang KL, Liz R, Schenkel EP, Fröde TS (2007) Anti-inflammatory evaluation of Solidago chilensis Meyen in a murine model of pleurisy. J Ethnopharmacol 113:346–353

    Article  PubMed  Google Scholar 

  • Halliwell B, Gutteridge JMC (2006) Free radicals in biology and medicine, 4th edn. Clarendon, Oxford

    Google Scholar 

  • Ham M, Kaunitz JD (2007) Gastroduodenal defense. Curr Opin Gastroenterol 23:607–616

    Article  PubMed  Google Scholar 

  • Hara N, Okabe S (1985) Effects of gefarnate on acute gastric lesions in rats. Nihon Yakurigaku Zasshi 85:443–446

    Article  CAS  PubMed  Google Scholar 

  • Hong CO, Lee HA, Rhee CH, Choung SY, Lee KW (2013) Separation of the antioxidant compound quercitrin from Lindera obtusiloba Blume and its antimelanogenic effect on B16F10 melanoma cells. Biosci Biotechnol Biochem 77:58–64

    Article  CAS  PubMed  Google Scholar 

  • Johansson ME, Sjövall H, Hansson GC (2013) The gastrointestinal mucus system in health and disease. Nat Rev Gastroenterol Hepatol 10:352–361

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones MP (2006) The role of psychosocial factors in peptic ulcer disease: beyond Helicobacter pylori and NSAIDs. J Psychosom Res 60:407–412

    Article  PubMed  Google Scholar 

  • Kangwan N, Park JM, Kim EH, Hahm KB (2014) Quality of healing of gastric ulcers: natural products beyond acid suppression. World J Gastrointest Pathophysiol 5:40–47

    Article  PubMed  PubMed Central  Google Scholar 

  • Kaplan KA, Odabasoglu F, Halici Z, Halici M, Cadirci E, Atalay F, Aydin O, Cakir A (2012) Alpha-lipoic acid protects against indomethacin-induced gastric oxidative toxicity by modulating antioxidant system. J Food Sci 77:H224–H230

    Article  CAS  PubMed  Google Scholar 

  • Konturek SJ, Brzozowski T, Majka J, Szlachcic A, Bielanski W, Stachura J, Otto W (1993) Fibroblast growth factor in gastroprotection and ulcer healing: interaction with sucralfate. Gut 34:881–887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubecova M, Kolostova K, Pinterova D, Kacprzak G, Bobek V (2011) Cimetidine: an anticancer drug? Eur J Pharm Sci 18:439–444

    Article  Google Scholar 

  • Kubo K, Uehara A, Kubota T, Nozu T, Moriya M, Watanabe Y, Shoji E, Santos SB, Harada K, Kohgo Y (1995) Effects of ranitidine on gastric vesicles containing H+,K(+)-adenosine triphosphatase in rats. Scand J Gastroenterol 30:944–951

    Article  CAS  PubMed  Google Scholar 

  • Laine L, Takeuchi K, Tarnawski A (2008) Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 135:41–60

    Article  CAS  PubMed  Google Scholar 

  • Lee BH, Kim N, Nam RH, Lee JY, Lee HS, Lee CH, Park JH, Lee DH (2014) Difficult establishment of a chronic nonsteroidal anti-inflammatory drugs induced gastric inflammation rat model due to gastric adaptation and small bowel damage. Korean J Gastroenterol 63:341–347

    Article  PubMed  Google Scholar 

  • Liz R, Vigil SV, Goulart S, Moritz MI, Schenkel EP, Fröde TS (2008) The anti-inflammatory modulatory role of Solidago chilensis Meyen in the murine model of the air pouch. J Pharm Pharmacol 60:515–521

    Article  CAS  PubMed  Google Scholar 

  • Lorenzi H, Matos FJA (2002) Plantas Medicinais no Brasil-nativas e exoticas: Solidago chilensis Meyen. Instituto Plantarum de Estudos da Flora, São Paulo, pp 170–171

    Google Scholar 

  • Malfertheiner P, Chan FKL, Mccoll KEL (2009) Peptic ulcer disease. Lancet 374:1449–1461

    Article  CAS  PubMed  Google Scholar 

  • Mei XT, Xu DH, Xu SK, Zheng YP, Xu SB (2013) Zinc(II)-curcumin accelerates the healing of acetic acid-induced chronic gastric ulcers in rats by decreasing oxidative stress and downregulation of matrix metalloproteinase-9. Food Chem Toxicol 60:448–454

    Article  CAS  PubMed  Google Scholar 

  • Mok SY, Lee S (2013) Identification of flavonoids and flavonoid rhamnosides from Rhododendron mucronulatum for. albiflorum and their inhibitory activities against aldose reductase. Food Chem 136:969–974

    Article  CAS  PubMed  Google Scholar 

  • Mors WB, Rizzini CT, Pereira NA (2000) Medicinal plants of Brazil. Reference, Algonac, p 65

    Google Scholar 

  • Mota da Silva L, Boeing T, Somensi LB, Cury BJ, Bispo Steimbach VM, Oliveira Silveria AC, Niero R, Cechinel Filho V, Santin JR, de Andrade SF (2015) Evidence of gastric ulcer healing activity of Maytenus robusta Reissek: in vitro and in vivo studies. J Ethnopharmacol 175:75–85

    Article  PubMed  Google Scholar 

  • Naito Y, Yoshikawa T, Yoshida N, Kondo M (1998) Role of oxygen radical and lipid peroxidation in indomethacin-induced gastric mucosal injury. Dig Dis Sci 43:30S–34S

    CAS  PubMed  Google Scholar 

  • Nishida T, Tsuji S, Kimura A, Tsujii M, Ishii S, Yoshio T, Shinzaki S, Egawa S, Irie T, Yasumaru M, Iijima H, Murata H, Kawano S, Hayashi N (2006) Endothelin-1, an ulcer inducer, promotes gastric ulcer healing via mobilizing gastric myofibroblasts and stimulates production of stroma-derived factors. Am J Physiol Gastrointest Liver Physiol 290:1041–1050

    Article  Google Scholar 

  • Okabe S, Pfeiffer CJ (1972) Chronicity of acetic acid ulcer in the rat stomach. Am J Dig Dis 17:619–629

    Article  CAS  PubMed  Google Scholar 

  • Périco LL, Heredia-Vieira SC, Beserra FP, de Cássia Dos Santos R, Weiss MB, Resende FA, Dos Santos Ramos MA, Bonifácio BV, Bauab TM, Varanda EA, de Gobbi JI, da Rocha LR, Vilegas W, Hiruma-Lima CA (2015) Does the gastroprotective action of a medicinal plant ensure healing effects? An integrative study of the biological effects of Serjania marginata Casar. (Sapindaceae) in rats. J Ethnopharmacol 172:312–324

    Article  PubMed  Google Scholar 

  • Ramakrishnan K, Salinas RC (2007) Peptic ulcer disease. Am Fam Physician 76:1005–1012

    PubMed  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, Meranze D, Gruenstein M, Siplet H (1945) A simple method for the uniform production of gastric ulceration in the rat. Gastroenterology 5:43–61

    Google Scholar 

  • Shimoyama AT, Santin JR, Machado ID, de Oliveira e Silva AM, de Melo IL, Mancini-Filho J, Farsky SH (2013) Antiulcerogenic activity of chlorogenic acid in different models of gastric ulcer. Naunyn Schmiedebergs Arch Pharmacol 386:5–14

    Article  CAS  PubMed  Google Scholar 

  • Szabo S (1987) Mechanisms of mucosal injury in the stomach and duodenum: time-sequence analysis of morphologic, functional, biochemical and histochemical studies. Scand J Gastroenterol Suppl 127:21–28

    Article  CAS  PubMed  Google Scholar 

  • Szabo S (2014) “Gastric cytoprotection” is still relevant. J Gastroenterol Hepatol 29:124–132

    Article  CAS  PubMed  Google Scholar 

  • Takeuchi K (2012) Pathogenesis of NSAID-induced gastric damage: importance of cyclooxygenase inhibition and gastric hypermotility. World J Gastroenterol 18:2147–2160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tamura EK, Jimenez RS, Waismam K, Gobbo-Neto L, Lopes NP, Malpezzi-Marinho EA, Marinho EA, Farsky SH (2009) Inhibitory effects of Solidago chilensis Meyen hydroalcoholic extract on acute inflammation. J Ethnopharmacol 122:478–485

    Article  PubMed  Google Scholar 

  • Tarnawski AS (2005) Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 50:24–33

    Article  Google Scholar 

  • Tarnawski A, Ahluwalia A, Jones MK (2013) Gastric cytoprotection beyond prostaglandins: cellular and molecular mechanisms of gastroprotective and ulcer healing actions of antacids. Curr Pharm Des 19:126–132

    CAS  PubMed  Google Scholar 

  • Teves MR, Rotelli AE, Wendel GH, Paredes JD, Giraudo E, Petenatti ME, Pelzer LE (2015) Records of medicinal plants utilized as gastroprotective and for treatment of gastrointestinal ulcers, gastritis, and heartburn in Argentina: a survey of the literature. J Herbs Spices Med Plants 21:333–371

    Article  Google Scholar 

  • Thomson AB, Sauve MD, Kassam N, Kamitakahara H (2010) Safety of the long-term use of proton pump inhibitors. World J Gastroenterol 16:2323–2330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vellosa JCR, Regasini LO, Khalil NM, da Silva BV, Khalil OAK, Manente FA, Netto HP, de Faria Oliveira OMM (2011) Antioxidant and cytotoxic studies for kaempferol, quercetin and isoquercitrin. Eclet Quím 36:2

    Article  Google Scholar 

  • Vellosa JC, Regasini LO, Belló C, Schemberger JA, Khalil NM, de Araújo M-GA, da Silva BV, Brunetti IL, de Faria Oliveira OM (2015) Preliminary in vitro and ex vivo evaluation of afzelin, kaempferitrin and pterogynoside action over free radicals and reactive oxygen species. Arch Pharm Res 38:1168–1177

    Article  CAS  PubMed  Google Scholar 

  • Wallace JL (2008) Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn’t the stomach digest itself? Physiol Rev 88:1547–1565

    Article  CAS  PubMed  Google Scholar 

  • Watanabe T, Arakawa T, Fukuda T, Higuchi K, Kobayashi K (1997) Role of neutrophils in a rat model of gastric ulcer recurrence caused by interleukin-1 beta. Am J Pathol 150:971–979

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu GH, Ryoo IJ, Kim YH, Choo SJ, Yoo ID (2009) Free radical scavenging and antielastase activities of flavonoids from the fruits of Thuja orientalis. Arch Pharm Res 32:275–282

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto A (1975) Proteolytic enzymes. In: REED G (ed) Enzymes in food processing, 2nd edn. Academic, London, pp 123–179

    Chapter  Google Scholar 

  • Yang YX (2012) Chronic proton pump inihibitor therapy and calcium metabolism. Curr Gastroenterol Rep 14:473–479

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang JC, Lu CW, Lin CJ (2014) Treatment of Helicobacter pylori infection: current status and future concepts. World J Gastroenterol 20:5283–5293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young OT, Ok AB, Jung JE, Sang PJ, Jong PS, Wook BH, Hahm KB (2008) Accelerated ulcer healing and resistance to ulcer recurrence with gastroprotectants in rat model of acetic acid-induced gastric ulcer. J Clin Biochem Nutr 42:204–214

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sérgio Faloni de Andrade.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Barros, M., Mota da Silva, L., Boeing, T. et al. Pharmacological reports about gastroprotective effects of methanolic extract from leaves of Solidago chilensis (Brazilian arnica) and its components quercitrin and afzelin in rodents. Naunyn-Schmiedeberg's Arch Pharmacol 389, 403–417 (2016). https://doi.org/10.1007/s00210-015-1208-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-015-1208-0

Keywords

Navigation