Effects of Sumsu (Bufonis venenum) Pharmacopuncture Treatment on Depression in Mice

  • Choi, Min-Ji (Department of Neuropsychiatry, College of Korean Medicine, Kyung Hee University) ;
  • Kim, Ka-Na (Department of Neuropsychiatry, College of Korean Medicine, Kyung Hee University) ;
  • Lee, Jae-Eun (Department of Neuropsychiatry, College of Korean Medicine, Kyung Hee University) ;
  • Suh, Jin-Woo (Department of Neuropsychiatry, College of Korean Medicine, Kyung Hee University) ;
  • Kim, Sung-Chul (Department of Acupuncture & Moxibustion, Wonkwang Gwangju Oriental Medical Hospital) ;
  • Kwon, Ki Rok (Research Center of Pharmacopuncture Medicine, Korean Pharmacopuncture Institute) ;
  • Cho, Seung-Hun (Department of Neuropsychiatry, College of Korean Medicine, Kyung Hee University)
  • Received : 2013.10.10
  • Accepted : 2014.04.10
  • Published : 2014.06.30


Objectives: The main objective of this study was to evaluate the anti-depressant effects of pharmacopuncture using sumsu (Bufonis venenum). Methods: Animals were divided into three groups (control, sham, and experimental), with eight mice per group. The sham and the experimental groups were exposed to 2 hours of immobilization stress daily for 14 days. They were also injected with normal saline (sham) or subjected to pharmacopuncture with sumsu at the acupoints HT7, SP6, and GV20 (experimental). The depression or anxiety-like behaviors of the mice in each group were evaluated 1 day after treatment. Results: There was no difference in locomotor activity between the groups during the open-field test; i.e., all groups had normal motor function. However, the open-field and the forced-swimming tests revealed that depression and anxiety-like behaviors were decreased significantly in the group treated with sumsu pharmacopuncture. Conclusion: Sumsu pharmacopuncture attenuated depressive or anxiety-like behavior in mice stressed with chronic immobilization. These results suggest that sumsu pharmacopuncture has therapeutic potential for treating neuropsychiatric disorders such as anxiety or depression disorder.


  1. Cowen PJ. Serotonin and depression: pathophysiological mechanism or marketing myth? Trends Pharmacol Sci. 2008;29(9):433-6.
  2. Chen JX, Li W, Zhao X, Yang JX. Effects of the Chinese traditional prescription Xiaoyaosan decoction on chronic immobilization stress-induced changes in behavior and brain BDNF, TrkB, and NT-3 in rats. Cellular and Molecular Neurobiology. 2008;28(5):745-55.
  3. Yin CS, Jeong HS, Park HJ, Baik Y, Yoon MH, Choi CB, et al. A proposed transpositional acupoint system in a mouse and rat model. Research in Veterinary Science. 2008;84(2):159-65.
  4. Reynolds EH. Brain and mind: a challenge for WHO. Lancet. 2003;361(9373):1924-5.
  5. Murray CLJ, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: global burden of disease study. The Lancet. 1997;349:1498-504.
  6. Keith SJ, Matthews SM. The value of psychiatric treatment: its efficacy in severe mental disorders. Psychoparmacol Bull. 1993;29(4):427-30.
  7. Ju YL, Chi X, Liu JX. Forty cases of insomnia treated by suspended moxibustion at Baihui (GV20). J Tradit Chin Med. 2009;29(2):95-6.
  8. Wynn SG, Luna SPL, Liu H. Global acupuncture research: previously untranslated studies. Studies from Brazil. In: Schoen AM, editor. Veterinary Acupuncture: Ancient Art to Modern Medicine. St Louis: Mosby; 2001. p. 53-7.
  9. Joo HJ. [Researches on Parmacopuncture]. Korea Institute of Oriental medicine. 1995;5:193-210. Korean.
  10. Chen KK, Kovarikove A. Pharmacology and toxicology of toad venom. J Pharm Sci. 1967;56(12):1535-41.
  11. Wang LH, Song KZ. Studies on the clinical application of Venenum Bufonis. Chin. J. Mod. Appl. Pharm. 2006;23:618-20.
  12. Prassas I, Diamandis EP. Novel therapeutic applications of cardiac glycosides. Nat Rev Drug Discov. 2008;7(11):926-35.
  13. Han KQ, Huang G, Gu W, Su YH, Huang XQ, Ling CQ. Anti-tumor activities and apoptosis-regulated mechanisms of bufalin on the orthotopic transplantation tumor model of human hepatocellular carcinoma in nude mice. World J Gastroenterol. 2007;13(24):3374-9.
  14. Hashimoto S, Jing Y, Kawazoe N, Masuda S, Nakajo S, Yoshida T, et al. Bufalin reduces the level of topoisomerase II in human leukemia cells and affects the cytotoxicity of anticancer drugs. Leuk Res. 1997;21(9):875-83.
  15. Watabe M, Ito K, Masuda Y, Nakajo S, Nakaya K. Activation of AP-1 is required for bufalin-induced apoptosis in human leukemia U937 cells. Oncogene. 1998;16(6):779-87.
  16. Yu CH, Kan SF, Pu HF, Jea Chien E, Wang PS. Apoptotic signaling in bufalin-and cinobufagin-treated androgen-dependent and-independent human prostate cancer cells. Cancer Sci. 2008;99(12):2467-76.
  17. Hong SH, Choi YH. Bufalin induces apoptosis through activation of both the intrinsic and extrinsic pathways in human bladder cancer cells. Oncol Rep. 2012;27(1):114-20.
  18. Lee HJ, Koung FP, Kwon KR, Kang DI, Lorenzo C, Yang PY, et al. Comparative Analysis of the Bufonis Venenum by Using TLC, HPLC, and LC-MS for Different Extraction Methods. J Pharmacopunct. 2012;15(4):52-65.
  19. Stockmeier CA. Neurobiology of Serotonin in Depression and Suicide. Annals of the New York Academy of Sciences. 1997;836:220-32.
  20. Neumeister A, Young T, Stastny J. Implications of genetic research on the role of the serotonin in depression: emphasis on the serotonin type 1A receptor and the serotonin transporter. Psychopharmacology (Berl). 2004;174(4):512-24.
  21. Linde K, Knuppel L. Large-scale observational studies of Hypericum extracts in patients with depressive disorders-a systematic review. Phytomedicine. 2005:12(1-2):148-57.
  22. Strausbaugh HJ, Dallman MF, Levine JD. Repeated, but not acute, stress suppresses inflammatory plasma extravasation. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(25):14629-34.
  23. Albonetti ME, Farabollini F. Effects of single and repeated restraint on the social behavior of male rats. Physiology & Behavior. 1993;53(5):937-42.
  24. Beck KD, Luine VN. Sex differences in behavioral and neurochemical profiles after chronic stress: role of housing conditions. Physiology & Behavior. 2002;75(5):661-73.
  25. Regenthal R, Koch H, Kohler C, Preiss R, Krugel U. Depression-like deficits in rats improved by subchronic modafinil. Psychopharmacology (Berl). 2009;204(4):627-39.
  26. Belzung C, Crusio WE, Gerlai RT(Eds.). Measuring exploratory behavior, Handbook of Molecular Genetic Techniques for Brain and Behavior Research (Techniques in the Behavioral and Neural Sciences). Amsterdam: Elsevier; p. 739-49.
  27. Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol. 2003;463(1-3):3-33.
  28. Kitada Y, Miyauchi T, Satoh A, Satoh S. Effects of antidepressants in the rat forced swimming test. Eur J Pharmacol. 1981;72(2-3):145-52.
  29. Cryan JF, Valentino RJ, Lucki I. Assessing substrates underlying the behavioral effects of antidepressants using the modified rat forced swimming test. Neurosci Biobehav Rev. 2005;29(4-5):547-69.
  30. Porsolt RD, Bertin A, Blavet N, Deniel M, Jalfre M. Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol. 1979;57(2-3):201-10.
  31. Satoh H. Acute effects of acupuncture treatment with Baihui (GV20) on human arterial stiffness and wave reflection. J Acupunct Meridian Stud. 2009;2(2):130-4.
  32. Zhao NX, Guo RL, Ren QY, Guo RF, Pan N. Influence of moxibustion of Baihui (GV20) on hemodynamics of common carotid artery in healthy subjects. Zhen Ci Yan Jiu. 2007;32(4):252-4.
  33. Moore A, McQuay H. Bandolier's little book of making sense of the medical evidence. Oxford. (UK): Oxford University Press.; 2006.
  34. Watabe M, Kawazoe N, Masuda Y, Nakajo S, Nakaya K. Bcl-2 protein inhibits bufalin-induced apoptosis through inhibition of mitogen-activated protein kinase activation in human leukemia U937 cells. Cancer Res. 1997;57(15):3097-100.
  35. Bae WS. [The succession and recreation of oriental medicine]. Korea Institute of Science and Technology Information. 1989;10(2):9-17. Korean.
  36. Fujiwara K, Ohta Y, Ogata I. [Treatment trial of traditional oriental medicine in chronic viral hepatitis]. In: Ohta Y (ed). New Trends in Peptic Ulcer and Chronic Hepatitis: Part II. Chronic Hepatitis. Tokyo: Excerpta Medica; 1987. p. 141-6. Japanese.
  37. Masuda Y, Kawazoe N, Nakajo S, Yoshida T, Kuroiwa Y, Nakaya K. Bufalin induces apoptosis and influences the expression of apoptosis-related genes in human leukemia cells. Leuk Res. 1995;19(8):549-56.
  38. Jing Y, Ohizumi H, Kawazoe N, Hashimoto S, Masuda Y, Nakajo S, et al. Selective inhibitory effect of bufalin on growth of human tumor cells in vitro: association with the induction of apoptosis in leukemia HL-60 cells. Jpn J Cancer Res. 1994;85(6):645-51.
  39. Steyn PS, van Heerden FR. Bufadienolides of plant and animal origin. Nat Prod Rep. 1998;15(4):397-413.
  40. Schoner W, Scheiner-Bobis G. Endogenous and exogenous cardiac glycosides: their roles in hypertension, salt metabolism, and cell growth. Am J Physiol Cell Physiol. 2007;293(2):509-36.
  41. Wang J, Jin Y, Xu Z, Zhenq Z, Wan S. Involvement of caspase-3 activity and survivin downregulation in cinobufocini-induced apoptosis in A 549 cells. Exp Biol Med (Maywood). 2009;234(5):566-72.
  42. Li D, Qu X, Hou K, Zhang Y, Dong Q, Teng Y, et al. PI3K/ Akt is involved in bufalin-induced apoptosis in gastric cancer cells. Anticancer Drugs. 2009;20(1):59-64.
  43. Giri B, Gomes A, Debnath A, Saha A, Biswas AK, Dasqupta SC, et al. Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo melanostictus, Schneider) skin extract on U937 and K562 cells. Toxicon. 2006;48(4):388-400.
  44. Huang C, Chen A, Guo M, Yu J. Membrane dielectric responses of bufalin-induced apoptosis in HL-60 cells detected by an electrorotation chip. Biotechnol Lett. 2007;29(9):1307-13.
  45. Kawazoe N, Watabe M, Masuda Y, Nakajo S, Nakaya K. Tiam1 is involved in the regulation of bufalin-induced apoptosis in human leukemia cells. Oncogene. 1999;18(15):2413-21.

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