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Arctigenin Exhibits Relaxation Effect on Bronchus by Affecting Transmembrane Flow of Calcium

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Abstract

Arctigenin, a lignan extract from Arctium lappa (L.), exhibits anti-inflammation, antioxidation, vasodilator effects, etc. However, the effects of arctigenin on bronchus relaxation are not well investigated. This study aimed to investigate how arctigenin regulates bronchus tone and calcium ion (Ca2+) flow. Trachea strips of guinea pigs were prepared for testing the relaxation effect of arctigenin to acetylcholine, histamine, KCl, and CaCl2, respectively. Furthermore, l-type calcium channel currents were detected by patch–clamp, and intracellular Ca2+ concentration was detected by confocal microscopy. The results showed that arctigenin exhibited relaxation effect on tracheae to different constrictors, and this was related to decreasing cytoplasmic Ca2+ concentration by inhibiting Ca2+ influx partly through l-type calcium channel as well as promoting Ca2+ efflux. In summary, this study provides new insight into the mechanisms by which arctigenin exhibits relaxation effect on bronchus and suggests its potential use for airway disease therapy.

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References

  1. Janssen LJ, Killian K (2006) Airway smooth muscle as a target of asthma therapy: history and new directions. Respir Res 7:123–134

    Article  PubMed  Google Scholar 

  2. Amrani Y, Panettieri RAJ (2002) Modulation of calcium homeostasis as a mechanism for altering smooth muscle responsiveness in asthma. Curr Opin Allergy Clin Immunol 2:39–45

    Article  PubMed  Google Scholar 

  3. Huxley AF (2000) Cross-bridge action: present views, prospects, and unknowns. J Biomech 33:1189–1195

    Article  PubMed  CAS  Google Scholar 

  4. Somlyo AP, Somlyo AV (2003) Ca2+ sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev 83:1325–1358

    PubMed  CAS  Google Scholar 

  5. Gunst SJ, Wu MF (2001) Selected contribution: plasticity of airway smooth muscle stiffness and extensibility: role of length-adaptive mechanisms. J Appl Physiol 90:741–749

    PubMed  CAS  Google Scholar 

  6. Tang DD, Gunst SJ (2001) Signal transduction in smooth muscle - selected contribution: roles of focal adhesion kinase and paxillin in the mechanosensitive regulation of myosin phosphorylation in smooth muscle. J Appl Physiol 91:1452–1459

    PubMed  CAS  Google Scholar 

  7. Hirota S, Helli P, Janssen LJ (2007) Ionic mechanisms and Ca2+ handling in airway smooth muscle. Eur Respir J 30:114–133

    Article  PubMed  CAS  Google Scholar 

  8. Zhao Z, Miao Y, Pan P, Cheng B, Bai G, Wu H (2013) Qingfei Xiaoyan Wan alleviates asthma through multi-target network regulation. BMC Complement Altern Med 13:206–215

    Article  PubMed  Google Scholar 

  9. Wang L, Zhao F, Liu K (2008) Advances in studies on pharmacological effect of arctiin and arctigenin. Chin Tradit Herb Drugs 39:467–470

    Google Scholar 

  10. Cheng B, Hou Y, Wang L, Dong L, Peng J, Bai G (2012) Dual-bioactivity-based liquid chromatography-coupled quadrupole time-of-flight mass spectrometry for NF-kappaB inhibitors and beta2AR agonists identification in Chinese Medicinal Preparation Qingfei Xiaoyan Wan. Anal Bioanal Chem 404:2445–2452

    Article  PubMed  CAS  Google Scholar 

  11. 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 122:457–462

    Article  PubMed  CAS  Google Scholar 

  12. Hyam SR, Lee IA, Gu W, Kim KA, Jeong JJ, Jang SE, Han MJ, Kim DH (2013) Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages. Eur J Pharmacol 708:21–9

    Article  PubMed  CAS  Google Scholar 

  13. Somlyo AP, Somlyo AV (2004) Signal transduction through the RhoA/Rho-kinase pathway in smooth muscle. J Muscle Res Cell Motil 25:613–615

    Article  PubMed  Google Scholar 

  14. Aworet-Samseny RRR, Souza A, Kpahe F, Konate K, Datte JY (2011) Dichrostachys cinerea (L.) Wight et Arn (Mimosaceae) hydro-alcoholic extract action on the contractility of tracheal smooth muscle isolated from guinea-pig. BMC Complement Altern Med 11:23

    Article  PubMed  Google Scholar 

  15. Gui Y, Wang ZY, Sun XR, Walsh MP, Li JJ, Gao J, Zheng XL (2011) Uridine adenosine tetraphosphate induces contraction of airway smooth muscle. Am J Physiol-Lung C 301:L789–L794

    Article  CAS  Google Scholar 

  16. Devillier P, Advenier C, Drapeau G, Marsac J, Regoli D (1988) Comparison of the effects of epithelium removal and of an enkephalinase inhibitor on the neurokinin–induced contractions of guinea–pig isolated trachea. Brit J Pharmacol 94:675–684

    Article  CAS  Google Scholar 

  17. Zhao L, Lou JS, Wu H, Yin YQ, Kang Y (2012) Effects of taurine-magnesium coordination compound on ionic channels in rat ventricular myocytes of arrhythmia induced by ouabain. Biol Trace Elem Res 147:275–284

    Article  PubMed  CAS  Google Scholar 

  18. Paredes RM, Etzler JC, Watts LT, Zheng W, Lechleiter JD (2008) Chemical calcium indicators. Methods 46:143–151

    Article  PubMed  CAS  Google Scholar 

  19. Meurs H, Dekkers BGJ, Maarsingh H, Halayko AJ, Zaagsma J, Gosens R (2013) Muscarinic receptors on airway mesenchymal cells: novel findings for an ancient target. Pulmonol Pharmacol Ther 26:145–155

    Article  CAS  Google Scholar 

  20. McFadzean I, Gibson A (2002) The developing relationship between receptor–operated and store–operated calcium channels in smooth muscle. Brit J Pharmacol 135:1–13

    Article  CAS  Google Scholar 

  21. Barnes PJ (1993) Muscarinic receptor subtypes in airways. Life Sci 52:521–527

    Article  PubMed  CAS  Google Scholar 

  22. Gunst SJ, Stropp JQ, Flavahan NA (1989) Muscarinic receptor reserve and beta-adrenergic sensitivity in tracheal smooth muscle. J Appl Physiol 67:1294–1298

    PubMed  CAS  Google Scholar 

  23. van Koppen CJ, Rodrigues De Miranda JF, Beld AJ, Hermanussen MW, Lammers JW, van Ginneken CA (1985) Characterization of the muscarinic receptor in human tracheal smooth muscle. Naunyn Schmiedeberg’s Arch Pharmacol 331:247–252

    Article  Google Scholar 

  24. Hisada T, Kurachi Y, Sugimoto T (1990) Properties of membrane currents in isolated smooth muscle cells from guinea-pig trachea. Pflugers Arch 416:151–161

    Article  PubMed  CAS  Google Scholar 

  25. Marthan R, Martin C, Amedee T, Mironneau J (1989) Calcium channel currents in isolated smooth muscle cells from human bronchus. J Appl Physiol 66:1706–1714

    PubMed  CAS  Google Scholar 

  26. Valverde MA, Cantero-Recasens G, Garcia-Elias A, Jung C, Carreras-Sureda A, Vicente R (2011) Ion channels in asthma. J Biol Chem 286:32877–32882

    Article  PubMed  CAS  Google Scholar 

  27. Waterman SA (2000) Voltage-gated calcium channels in autonomic neuroeffector transmission. Prog Neurobiol 60:181–210

    Article  PubMed  CAS  Google Scholar 

  28. Deshpande DA, Walseth TF, Panettieri RA, Kannan MS (2003) CD38-cyclic ADP-ribose-mediated Ca2+ signaling contributes to airway smooth muscle hyperresponsiveness. FASEB J 17:452

    PubMed  CAS  Google Scholar 

  29. Tliba O, Deshpande D, Chen H, Van Besien C, Kannan M, Panettieri RA, Amrani Y (2003) IL-13 enhances agonist-evoked calcium signals and contractile responses in airway smooth muscle. Brit J Pharmacol 140:1159–1162

    Article  CAS  Google Scholar 

  30. Gumral N, Naziroglu M, Ongel K, Beydilli ED, Ozguner F, Sutcu R, Caliskan S, Akkaya A (2009) Antioxidant enzymes and melatonin levels in patients with bronchial asthma and chronic obstructive pulmonary disease during stable and exacerbation periods. Cell Biochem Funct 27:276–283

    Article  PubMed  CAS  Google Scholar 

  31. Naziroglu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001

    Article  PubMed  CAS  Google Scholar 

  32. Naziroglu M (2012) Molecular role of catalase on oxidative stress-induced Ca2+ signaling and TRP cation channel activation in nervous system. J Recept Signal Transduct 32:134–141

    Article  CAS  Google Scholar 

  33. Halayko AJ, Amrani Y (2003) Mechanisms of inflammation-mediated airway smooth muscle plasticity and airways remodeling in asthma. Respir Physiol Neurobiol 137:209–222

    Article  PubMed  CAS  Google Scholar 

  34. Kang HS, Lee JY, Kim CJ (2008) Anti-inflammatory activity of arctigenin from Forsythiae Fructus. J Ethnopharmacol 116:305–312

    Article  PubMed  CAS  Google Scholar 

  35. Gosens R, Bromhaar M, Tonkes A, Schaafsma D, Zaagsma J, Nelemans SA, Meurs H (2004) Muscarinic M-3 receptor-dependent regulation of airway smooth muscle contractile phenotype. Brit J Pharmacol 141:943–950

    Article  CAS  Google Scholar 

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Acknowledgments

This study was financially supported by grants from the National Nature Science Fund (NNSF) of China (no. 81173638, 81373506) and the Ministry of Education Doctoral Fund (no. 20120031110042), Key Teacher Training Project of Heilongjiang Province (1155G61), and Chinese Postdoctoral Fund (20080440687). We appreciate the valuable comments from other members of our laboratories.

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The authors declare that they have no conflict of interest.

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Correspondence to Hong Wu or Min Jiang.

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Zhenying Zhao and Yongqiang Yin contributed equally to this article.

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Zhao, Z., Yin, Y., Wang, Z. et al. Arctigenin Exhibits Relaxation Effect on Bronchus by Affecting Transmembrane Flow of Calcium. Biol Trace Elem Res 156, 181–187 (2013). https://doi.org/10.1007/s12011-013-9839-9

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  • DOI: https://doi.org/10.1007/s12011-013-9839-9

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