An alternative method to reduce anaphylaxis by moxibustion



Jeong, Hyun-Ja;Nam, Sun-Young;Lee, Byong-Joo;Kim, Min-Gi;Kim, Jeong-Hwa;Kim, Hyung-Min

  • 투고 : 2014.03.15
  • 심사 : 2014.05.08
  • 발행 : 2014.05.31


Epinephrine is a critical drug for patients at risk for anaphylaxis. Here, we suggest moxibustion as an alternative method to reduce anaphylaxis. Moxibustion was applied to the Shimen (CV5) acupoint and found to attenuate compound 48/80-induced mortality. Capsazepine, a transient receptor potential vanilloid (TRPV) 1 antagonist, significantly improved overall survival rates compared to groups treated with moxibustion or 2-aminoethoxydiphenyl borate (an activator of TRPV1, 2, and 3). Probenecid (a TRPV2 agonist) also increased survival rate and reduced histamine levels. Survival rates increased by moxibustion and probenecid were completely inhibited by ruthenium red (a TRPV2 and 3 antagonist) and gadolinium chloride (general TRPV antagonist), respectively. Passive cutaneous anaphylaxis and ear swelling were significantly reduced by moxibustion and probenecid (p < 0.05). In cardiomyocytes, TRPV2 was over-expressed by compound 48/80 and histamine but this increased TRPV2 expression decreased to baseline with moxibustion and probenecid treatment. In addition, intracellular calcium levels increased by compound 48/80 were reduced by probenecid. Overall, these findings suggest that the reduction of anaphylaxis caused by moxibustion could represent a new mechanism of moxibustion related to the regulation of TRPV2 activation and promotion of epinephrine secretion.


anaphylaxis;moxibustion;transient receptor potential vanilloid2;epinephrine


  1. Olivera A, Eisner C, Kitamura Y, Dillahunt S, Allende L, Tuymetova G, Walford W, Meylan F, Diesner SC, Li L, Schnermann J, Proia RL, Rivera J. Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice. J Clin Invest. 2010;120:1429-1440.
  2. Toth BI, Geczy T, Griger Z, Dozsa A, Seltmann H, Kovacs L, Nagy L, Zouboulis CC, Paus R, Biro T. Transient receptor potential vanilloid-1 signaling as a regulator of human sebocyte biology. J Invest Dermatol. 2009;129:329-339.
  3. Vandana B, Saraswathy L, Suseeladevi GK, Sundaram KR, Kumar H. Positive impact of integrated amrita meditation technique on heart rate, respiratory rate and IgA on young healthy adults.TANG. 2013;3:e13.
  4. Weissgerber AJ. Methylene blue for refractory hypotension: a case report. AANA J. 2008;76:271-274.
  5. Muraki K, Iwata Y, Katanosaka Y, Ito T, Ohya S, Shigekawa M, Imaizumi Y. TRPV2 is a component of osmotically sensitive cation channels in murine aortic myocytes. Circ Res. 2003;93:829-838.
  6. Okazaki M, Aizawa S, Yamauchi M, Oguchi K. Effects of single moxibustion on cutaneous blood vessel and microvascular permeability in mice. Am J Chin Med. 1990;18:121-130.
  7. Robbins N, Koch SE, Rubinstein J. Targeting TRPV1 and TRPV2 for potential therapeutic interventions in cardiovascular disease. Transl Res. 2013;161:469-476.
  8. Rubinstein J, Lasko VM, Koch SE, Singh VP, Carreira V, Robbins N, Patel AR, Jiang M, Bidwell P, Kranias EG, Jones WK, Lorenz JN. Novel Role of Transient Receptor Potential Vanilloid 2 in the Regulation of Cardiac Performance. Am J Physiol Heart Circ Physiol. 2014;306:H574-H584.
  9. Schummer W, Schummer C, Wippermann J, Fuchs J. Anaphylactic shock: is vasopressin the drug of choice? Anesthesiology. 2004;101:1025-1027.
  10. Shibasaki K, Murayama N, Ono K, Ishizaki Y, Tominaga M. TRPV2 enhances axon outgrowth through its activation by membrane stretch in developing sensory and motor neurons. J Neurosci. 2010;30:4601-4612.
  11. Takayama S, Seki T, Watanabe M, Takashima S, Sugita N, Konno S, Takeda T, Arai H, Yambe T, Yaegashi N, Yoshizawa M, Maruyama S, Nitta S. Changes of blood flow volume in the superior mesenteric artery and brachial artery with abdominal thermal stimulation. Evid Based Complement Alternat Med. 2011;2011:214089.
  12. Lewinter RD, Scherrer G, Basbaum AI. Dense transient receptor potential cation channel, vanilloid family, type 2 (TRPV2) immunoreactivity defines a subset of motoneurons in the dorsal lateral nucleus of the spinal cord, the nucleus ambiguus and the trigeminal motor nucleus in rat. Neuroscience. 2008;151:164-173.
  13. Kim J, Kang D, Kang M, Kang B, Kang EB, Kang J, Go Y, Ko W, Kwak J, Ku H, Gwon SY, Gi Y, Kim G, Kim G, Kim K, Kim K, Kim DH, Kim M, Kim MC, Kim S, Kim S, Kim S, Kim S, Kim Y, Kim J, Kim J, Nam S, Doh T, Do H, Moon GY, Min G, Park KK, Park M, Park S, Park I, Park JG, Park J, Park JG, Park J, Park T, Bae J, Byun J, Seo SW, Seo H, Son K, Song CG, Shin HY, Sim EK, An S, Ahn J, Yang JY, Ok D, Yoon G, Yoon SS, Yoon Y, Yoon J, Lee KE, Lee K, Lee D, Lee MH, Lee S, Lee S, Lee SH, Lee SY, Lee S, Lee Y, Lee J, Lee JS, Lee J, Lee J, Lee J, Lee CH, Lee CH, Lim S, Lim S, Rheem HG, Jun H, Jeong B, Chung I, Jung J, Cho S, Cho W, Cho E, Joo S, Ji H, Cheon S, Choi I, Choi J, Choi JH, Han N, Han S, Huh E, Hong YJ, Hong J, Hwang M, Moon PD. A comparison of the effects of dexamethasone-pharmacopuncture and dexamethasone-oral administration based on traditional Korean medicine theory on anaphylactic reaction in mice. TANG. 2013;3:e24.
  14. Koch SE, Gao X, Haar L, Jiang M, Lasko VM, Robbins N, Cai W, Brokamp C, Varma P, Tranter M, Liu Y, Ren X, Lorenz JN, Wang HS, Jones WK, Rubinstein J. Probenecid: novel use as a non-injurious positive inotrope acting via cardiac TRPV2 stimulation. J Mol Cell Cardiol. 2012;53:134-144.
  15. Lee SG, Lee H, Nam TG, Eom SH, Heo HJ, Lee CY, Kim DO. Neuroprotective effect of caffeoylquinic acids from Artemisia princeps Pampanini against oxidative stress-induced toxicity in PC-12 cells. J Food Sci. 2011;76:C250-256.
  16. Murata M, Cingolani E, McDonald AD, Donahue JK, Marban E. Creation of a genetic calcium channel blocker by targeted gem gene transfer in the heart. Circ Res. 2004;95:398-405.
  17. Iwata Y, Katanosaka Y, Arai Y, Komamura K, Miyatake K, Shigekawa M. A novel mechanism of myocyte degeneration involving the Ca2+-permeable growth factor-regulated channel. J Cell Biol. 2003;161:957-967.
  18. Felix SB, Baumann G, Niemczyk M, Hashemi T, Ochsenfeld G, Ahmad Z, Shirani S, Blomer H. Effects of histamine H1- and H2-receptor antagonists on cardiovascular function during systemic anaphylaxis in guinea pigs. Agents Actions. 1991;32:245-252.
  19. Hu HZ, Gu Q, Wang C, Colton CK, Tang J, Kinoshita-Kawada M, Lee LY, Wood JD, Zhu MX. 2-aminoethoxydiphenyl borate is a common activator of TRPV1, TRPV2, and TRPV3. J Biol Chem. 2004;279:35741-35748.
  20. Inoue R, Hai L, Honda A. Pathophysiological implications of transient receptor potential channels in vascular function. Curr Opin Nephrol Hypertens. 2008;17:193-198.
  21. Johansson SG, Hourihane JO, Bousquet J, Bruijinzeel-Koomen C, Dreborg S, Haahtela T, Kowalski ML, Mygind N, Ring J, van Cauwenberge P, van Hage-Hamsten M, Wuthrich B, EAACI (the European Academy of Allergology and Cinical Immunology) nomenclature task force. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy. 2001;56:813-824.
  22. Kim CW, Figueroa A, Park CH, Kwak YS, Kim KB, Seo DY, Lee HR. Combined effects of food and exercise on anaphylaxis. Nutr Res Pract. 2013;7:347-351.
  23. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000;288:306-313.
  24. Baylie RL, Brayden JE. TRPV channels and vascular function. Acta Physiol (Oxf). 2001;203:99-116.
  25. Calderon E, Mendez J, Nazario S. Anaphylaxis diagnosis and treatment at an emergency department in Puerto Rico. P R Health Sci J. 2013;32:170-174.
  26. Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature. 1999;398:436-441.
  27. Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, Grant R, O'Donnell D, Nicoll RA, Shan NM, Julius D, Basbaum AI. Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci. 2011;31:5067-5077.
  28. Choi GS, Han JB, Park JH, Oh SD, Lee GS, Bae HS, Jung SK, Cho YW, Ahn HJ, Min BI. Effects of moxibustion to zusanli (ST36) on alteration of natural killer cell activity in rats. Am J Chin Med. 2004;32:303-312.
  29. Couto M, de Diego A, Perpini M, Delgado L, Moreira A. Cough reflex testing with inhaled capsaicin and TRPV1 activation in asthma and comorbid conditions. J Investig Allergol Clin Immunol. 2013;23:289-301.
  30. Davis JB, Gray J, Gunthorpe MJ, Hatcher JP, Davey PT, Overend P, Harries MH, Latcham J, Clapham C, Atkinson K, Hughes SA, Rance K, Grau E, Harper AJ, Pugh PL, Rogers DC, Bingham S, Randall A, Sheardown SA. Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature. 2000;405:183-187.
  31. Deng H, Shen X. The Mechanism of Moxibustion: Ancient Theory and Modern Research. Evid Based Complement Alternat Med. 2013;2013:379291.
  32. Andrade EL, Luiz AP, Ferreira J, Calixto JB. Pronociceptive response elicited by TRPA1 receptor activation in mice. Neuroscience. 2008;152:511-520.

피인용 문헌

  1. 1. The potential anti-proliferative effect of β-sitosterol on human mast cell line-1 cells vol.93, pp.11, 2015, doi:10.5667/tang.2014.0011