, Volume 26, Issue 2, pp 521–530 | Cite as

Acid-gastric antisecretory effect of the ethanolic extract from Arctium lappa L. root: role of H+, K+-ATPase, Ca2+ influx and the cholinergic pathway

  • Luisa Mota da SilvaEmail author
  • Ligia de Moura Burci
  • Sandra Crestani
  • Priscila de Souza
  • Rita de Cássia Melo Vilhena de Andrade Fonseca da Silva
  • Nessana Dartora
  • Lauro Mera de Souza
  • Thales Ricardo Cipriani
  • José Eduardo da Silva-Santos
  • Eunice André
  • Maria Fernanda de Paula WernerEmail author
Original Article



Arctium lappa L., popularly known as burdock, is a medicinal plant used worldwide. The antiulcer and gastric-acid antisecretory effects of ethanolic extract from roots of Arctium lappa (EET) were already demonstrated. However, the mechanism by which the extract reduces the gastric acid secretion remains unclear. Therefore, this study was designed to evaluate the antisecretory mode of action of EET.

Materials and methods

The effects of EET on H+, K+-ATPase activity were verified in vitro, whereas the effects of the extract on cholinergic-, histaminergic- or gastrinergic-acid gastric stimulation were assessed in vivo on stimulated pylorus ligated rats. Moreover, ex vivo contractility studies on gastric muscle strips from rats were also employed.


The incubation with EET (1000 µg/ml) partially inhibited H+, K+-ATPase activity, and the intraduodenal administration of EET (10 mg/kg) decreased the volume and acidity of gastric secretion stimulated by bethanechol, histamine, and pentagastrin. EET (100–1000 µg/ml) did not alter the gastric relaxation induced by histamine but decreased acetylcholine-induced contraction in gastric fundus strips. Interestingly, EET also reduced the increase in the gastric muscle tone induced by 40 mM KCl depolarizing solution, as well as the maximum contractile responses evoked by CaCl2 in Ca2+-free depolarizing solution, without impairing the effect of acetylcholine on fundus strips maintained in Ca2+ -free nutritive solution.


Our results reinforce the gastric antisecretory properties of preparations obtained from Arctium lappa, and indicate that the mechanisms involved in EET antisecretory effects include a moderate reduction of the H+, K+-ATPase activity associated with inhibitory effects on calcium influx and of cholinergic pathways in the stomach muscle.


Burdock Pylorus ligation H+, K+-ATPase Calcium Acetylcholine Gastric fundus 



This work received grants from Fundação Araucária (Call 311/2014). Luisa Mota da Silva received a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil).

Compliance with ethcial standards

Conflict of interest

The authors declare that there was no conflict of interest.


  1. Ahangarpour A, Heidari H, Oroojan AA, Mirzavandi F, Nasr Esfehani K, Dehghan Mohammadi Z (2017) Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root’s hydro-alcoholic extract on nicotinamide-streptozotocin induced type 2 model of diabetes in male mice. Avicenna J Phytomed 7:169–179PubMedPubMedCentralGoogle Scholar
  2. Arya E, Saha S, Saraf SA, Kaithwas G (2013) Effect of fixed oil on experimental esophagitis in albino wistar rats. BioMed Res Int 2013:1–6CrossRefGoogle Scholar
  3. Buharalioğlu CK, Akar F (2002) The reactivity of serotonin, acetylcholine and kcl induced contractions to relaxant agents in the rat gastric fundus. Pharmacol Res 45:325–331CrossRefPubMedGoogle Scholar
  4. Burci LM, Pereira IT, da Silva LM, Rodrigues RV, Facundo VA, Militão JS, Santos AR, Marques MC, Baggio CH, Werner MF (2013) Antiulcer and gastric antisecretory effects of dichloromethane fraction and piplartine obtained from fruits of Piper tuberculatum Jacq. in rats. J Ethnopharmacol 148:165–174CrossRefPubMedGoogle Scholar
  5. Cabrini DA, Kyle DJ, Calixto JB (1996) A pharmacological analysis of receptor subtypes and the mechanisms mediating the biphasic response induced by kinins in the rat stomach fundus in vitro. J Pharmacol Exp Ther 277:299–307PubMedGoogle Scholar
  6. Caplan MJ (2007) The future of the pump. J Clin Gastroenterol 41:S217–S222CrossRefPubMedGoogle Scholar
  7. Chan YS, Cheng LN, Wu JH, Chan E, Kwan YW, Lee SM, Leung GP, Yu PH, Chan SW (2011) A review of the pharmacological effects of Arctium lappa (burdock). Inflammopharmacology 19:245–254CrossRefPubMedGoogle Scholar
  8. da Silva LM, Allemand A, Mendes DA, Dos Santos AC, André E, de Souza LM, Cipriani TR, Dartora N, Marques MC, Baggio CH, Werner MF (2013) Ethanolic extract of roots from Arctium lappa L. accelerates the healing of acetic acid-induced gastric ulcer in rats: involvement of the antioxidant system. Food Chem Toxicol 51:179–187CrossRefPubMedGoogle Scholar
  9. da Silva LM, Boeing T, Somensi LB, Cury BJ, Steimbach VM, 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 175:75–85CrossRefPubMedGoogle Scholar
  10. de Almeida AB, Sánchez-Hidalgo M, Martín AR, Luiz-Ferreira A, Trigo JR, Vilegas W, dos Santos LC, Souza-Brito AR, de la Lastra CA (2013) Anti-inflammatory intestinal activity of Arctium lappa L. (Asteraceae) in TNBS colitis model. J Ethnopharmacol 146:300–310CrossRefPubMedGoogle Scholar
  11. Döndaş NY, Kaplan M, Kaya D, Şingirik E (2009) The impact of extracellular and intracellular Ca2+ on ethanol-induced smooth muscle contraction. Acta Pharmacol Sin 30:1421–1427CrossRefPubMedPubMedCentralGoogle Scholar
  12. Dos Santos AC, Baggio CH, Freitas CS, Lepieszynski J, Mayer B, Twardowschy A, Missau FC, dos Santos EP, Pizzolatti MG, Marques MC (2008) Gastroprotective activity of the chloroform extract of the roots from Arctium lappa L. J Pharm Pharmacol 60:795–801CrossRefPubMedGoogle Scholar
  13. Dufner MM, Kirchhoff P, Remy C, Hafner P, Müller MK, Cheng SX, Tang LQ, Hebert SC, Geibel JP, Wagner CA (2005) The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands. Am J Physiol Gastrointest Liver Physiol 289:G1084–G1090CrossRefPubMedGoogle Scholar
  14. Eusebi LH, Rabitti S, Artesiani ML, Gelli D, Montagnani M, Zagari RM, Bazzoli F (2017) Proton pump inhibitos: risks of long-term use. J Gastroenterol Hepatol 32:1295–1302CrossRefPubMedGoogle Scholar
  15. Gentil M, Pereira JV, Sousa YT, Pietro R, Neto MD, Vansan LP, de Castro França S (2006) In vitro evaluation of the antibacterial activity of Arctium lappa as a phytotherapeutic agent used in intracanal dressings. Phytother Res 20:184–186CrossRefPubMedGoogle Scholar
  16. Hertz F, Cloarec A (1989) Comparative antiulcer and antisecretory effects of various calcium antagonists. Gen Pharmacol 20:635–640CrossRefPubMedGoogle Scholar
  17. Huang TC, Tsai SS, Liu LF, Liu YL, Liu HJ, Chuang KP (2010) Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model. World J Gastroenterol 16:4193–4199CrossRefPubMedPubMedCentralGoogle Scholar
  18. James AN, Ryan JP, Crowell MD, Parkman HP (2004) Regional gastric contractility alterations in a diabetic gastroparesis mouse model: effects of cholinergic and serotoninergic stimulation. Am J Physiol Gastrointest Liver Physiol 287:G612–G619CrossRefPubMedGoogle Scholar
  19. Jan M, Mughal MA, Tanwani RK, Aamir K, Ali M (2004) Evaluation of combined effect of verapamil and ranitidine on the volume and acidity of carbachol induced gastric secretion. J Ayub Med Coll Abbottabad 16:34–37PubMedGoogle Scholar
  20. Jan M, Orakzai SA, Tariq S, Javid M, Ahmad S, Haroon M, Qamar M (2005) Comparison of verapamil and cimetidine for their effects on volume and acidity of Carbachol induced gastric secretion in fasting rabbits. J Ayub Med Coll Abbottabad 17:11–14PubMedGoogle Scholar
  21. Kaithwas G, Majumdar DK (2010) Evaluation of antiulcer and antisecretory potential of Linum usitatissimum fixed oil and possible mechanism of action. Inflammopharmacology 18:137–145CrossRefPubMedGoogle Scholar
  22. Kamata K, Arai Y, Kasuya Y (1993) Mechanism of the contractile response to platelet-activating factor (PAF) of the rat stomach fundus. I. PAF-induced contractile response and calcium mobilization. Gen Pharmacol 24:1331–1336CrossRefGoogle Scholar
  23. Kangwan N, Park JM, Kim EH, Hahm KB (2014) Quality of healing of gastric ulcers: natural products beyond acid suppression. World J Gastrointest Pathophysiol 5:40–47CrossRefPubMedPubMedCentralGoogle Scholar
  24. Karaki H, Urakawa N, Kutsky P (1984) Potassium-induced contraction in smooth muscle. Nihon Heikatsukin Gakkai Zasshi 20:427–444CrossRefPubMedGoogle Scholar
  25. Klotz U (2009) Proton pump inhibitors—their pharmacological impact on the clinical management of acid-related disorders. Arzneimittelforschung 59:271–282PubMedGoogle Scholar
  26. Komori S, Bolton TB (1991) Calcium release induced by inositol 1,4,5-trisphosphate in single rabbit intestinal smooth muscle cells. J Physiol 433:495–517CrossRefPubMedPubMedCentralGoogle Scholar
  27. 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 30:944–951CrossRefPubMedGoogle Scholar
  28. Kwon K, Koong HS, Kang KH (2016) Effect of burdock extracts upon inflammatory mediator production. Technol Health Care 24:459–469CrossRefPubMedGoogle Scholar
  29. Lakshmi V, Singh N, Shrivastva S, Mishra SK, Dharmani P, Mishra V, Palit G (2010) Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats. Phytomedicine 17:569–574CrossRefPubMedGoogle Scholar
  30. Leonard SS, Keil D, Mehlman T, Proper S, Shi X, Harris GK (2006) Essiac tea: scavenging of reactive oxygen species and effects on DNA damage. J Ethnopharmacol 103:288–296CrossRefPubMedGoogle Scholar
  31. Lin SC, Lin CH, Lin CC, Lin YH, Chen CF, Chen IC, Wang LY (2002) Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride. J Biomed Sci 9:401–409PubMedGoogle Scholar
  32. Matsumoto T, Nishiyama M, Kobayashi T, Kasuya Y, Kamata K (2005) Effect of phorbol 12,13-dibutyrate on smooth muscle tone in rat stomach fundus. J Smooth Muscle Res 41:107–116CrossRefPubMedGoogle Scholar
  33. Milenov K, Todorov S, Vassileva M, Zamfirova R, Shahbazian A (1995) Different effects of H1 and H2 blockers on the tone and the contractile activity of guinea pig stomach fundus. Methods Find Exp Clin Pharmacol 17:609–613PubMedGoogle Scholar
  34. Miner P (2004) Review article: relief of symptoms in gastric acid-related diseases—correlation with acid suppression in rabeprazole treatment. Aliment Pharmacol Ther 20:20–29CrossRefPubMedGoogle Scholar
  35. Muller MJ, Prior T, Hunt RH, Rangachari PK (1993) H1 contractile and H2 relaxant receptors in canine gastric muscularis mucosae. Life Sci 52:PL49–PL53CrossRefPubMedGoogle Scholar
  36. Nandi J, King RL, Kaplan DS, Levine RA (1990) Mechanisms of gastric proton pump inhibition by calcium channel antagonists. J Pharmacol Exp Ther 252:1102–1107PubMedGoogle Scholar
  37. Pereira JV, Bergamo DC, Pereira JO, de França Castro S, Pietro RC, Silva-Sousa YT (2005) Antimicrobial activity of Arctium lappa constituents against microorganisms commonly found in endodontic infections. Braz Dent J 16:192–196CrossRefPubMedGoogle Scholar
  38. Rattmann YD, Terluk MR, Souza WM, Santos CA, Biavatti MW, Torres LB, Mesia-Vela S, Rieck L, da Silva-Santos JE, Marques MC (2005) Effects of alkaloids of Himatanthus lancifolius (Muell. Arg.) Woodson, Apocynaceae, on smooth muscle responsiveness. J Ethnopharmacol 100:268–275CrossRefPubMedGoogle Scholar
  39. Remy C, Kirchhoff P, Hafner P, Busque SM, Müeller MK, Geibel JP, Wagner CA (2007) Stimulatory pathways of the calcium-sensing receptor on acid secretion in freshly isolated human gastric glands. Cell Physiol Biochem 19:33–42CrossRefPubMedGoogle Scholar
  40. Schubert ML (2010) Gastric secretion. Curr Opin Gastroenterol 26:598–603CrossRefPubMedGoogle Scholar
  41. Schubert ML (2011) Gastric secretion. Curr Opin Gastroenterol 27:536–542CrossRefPubMedGoogle Scholar
  42. Wrzos HF, Tandon T, Ouyang A (2004) Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats. World J Gastroenterol 10:3292–3298CrossRefPubMedPubMedCentralGoogle Scholar
  43. Yao X, Forte JG (2003) Cell biology of acid secretion by the parietal cell. Annu Rev Physiol 65:103–131CrossRefPubMedGoogle Scholar
  44. Yucel E, Sancar M, Yucel A, Okuyan B (2016) Adverse drug reactions due to drug-drug interactions with proton pump inhibitors: assessment of systematic reviews with AMSTAR method. Expert Opin Drug Saf 15:223–236CrossRefPubMedGoogle Scholar
  45. Zhao F, Wang L, Liu K (2009) In vitro anti-inflammatory effects of arctigenin, a lignan from Arctium lappa L., through inhibition on iNOS pathway. J Ethnopharmacol 21:457–462CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Luisa Mota da Silva
    • 1
    • 2
    Email author
  • Ligia de Moura Burci
    • 1
  • Sandra Crestani
    • 3
  • Priscila de Souza
    • 1
    • 2
  • Rita de Cássia Melo Vilhena de Andrade Fonseca da Silva
    • 1
  • Nessana Dartora
    • 3
  • Lauro Mera de Souza
    • 3
  • Thales Ricardo Cipriani
    • 3
  • José Eduardo da Silva-Santos
    • 4
  • Eunice André
    • 1
  • Maria Fernanda de Paula Werner
    • 1
    Email author
  1. 1.Departamento de Farmacologia, Setor de Ciências BiológicasUniversidade Federal do ParanáCuritibaBrazil
  2. 2.Programa de Pós-Graduação em Ciências Farmacêuticas, Centro de Ciências da SaúdeUniversidade do Vale do ItajaíItajaíBrazil
  3. 3.Departamento de Bioquímica, Setor de Ciências BiológicasUniversidade Federal do ParanáCuritibaBrazil
  4. 4.Laboratório de Biologia Cardiovascular, Departmento de Farmacologia, Centro de Ciências BiológicasUniversidade Federal de Santa CatarinaFlorianópolisBrazil

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