대한약침학회지 (Journal of Pharmacopuncture)

  • 제21권2호
  • /
  • Pages.90-97
  • /
  • 2018
  • /
  • 2093-6966(pISSN)
  • /
  • 2234-6856(eISSN)
대한약침학회 (KOREAN PHARMACOPUNCTURE INSTITUTE)
권호 표지
DOI QR코드

DOI QR Code

Immunomodulatory effects of silymarin after subacute exposure to mice: A tiered approach immunotoxicity screening

  • Karimi, Gholamreza (Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences) ;
  • Hassanzadeh-Josan, Samed (Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences) ;
  • Memar, Bahram (Cancer Research Center, Faculty of Medicine, Mashhad University of Medical Sciences) ;
  • Esmaeili, Seyed-Alireza (Immunology Research Center, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences) ;
  • Riahi-Zanjani, Bamdad (Medical Toxicology Research Center, Mashhad University of Medical Sciences)
  • 투고 : 2017.12.23
  • 심사 : 2018.05.06
  • 발행 : 2018.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Silymarin is a flavonoid complex extracted from the Silybum marianum plant with a wide range of pharmacological and biochemical effects. In the present study, the immunomodulatory effects of silymarin were investigated in BALB/c mice. Silymarin was administered daily by intraperitoneal injection at doses of 50, 100 and 150 mg/kg for 14 consecutive days. Following the exposure, host hematological parameters, spleen cellularity and histopathological examination, as well as delayed-type hypersensitivity (DTH) responses, hemagglutination titers (HA), splenocyte cytokine production and lymphocyte proliferation assay were studied in all of the test groups of animals. The results showed that the low dose of silymarin (50 mg/kg) could stimulate both cellular and humoral immune functions in the treated hosts. In addition, silymarin at 100 mg/kg appeared to impact on DTH responses and lymphoproliferation. Based on the finding here, it would seem that silymarin has efficient immunostimulant properties. As a recommendation, the application of silymarin along with acupuncture technique (herbal acupuncture) can be thought as a good plan to modulate and enhance the immune system for the management of several immunodeficiency disorders. However, further studies are required to demonstrate this hypothesis.

키워드

참고문헌

  1. Farsam V, Hassan ZM, Zavaran-Hosseini A, Noori S, Mahdavi M, Ranjbar M. Antitumor and immunomodu- latory properties of artemether and its ability to reduce CD4+ CD25+ FoxP3+ T reg cells in vivo. Int Immunop-harmacol. 2011;11(11):1802-8. https://doi.org/10.1016/j.intimp.2011.07.008
  2. Riahi-Zanjani B, Balali-Mood M, Mohammadi E, Badie-Bostan H, Memar B, Karimi G. Safranal as a safe compound to mice immune system. Avicenna J Phytomed. 2015;5(5):441.
  3. Shirani K, Hassani FV, Razavi-Azarkhiavi K, Heidari S, Zanjani BR, Karimi G. Phytotrapy of cyclophospha-mide-induced immunosuppression. Environ Toxicol Pharmacol. 2015;39(3):1262-75. https://doi.org/10.1016/j.etap.2015.04.012
  4. Noori S, Taghikhani M, Hassan ZM, Allameha A, Mostafaei A. Tehranolide molecule modulates the immune response, reduce regulatory T cell and inhibits tumor growth in vivo. Molecul Immunol. 2010;47(7):1579-84. https://doi.org/10.1016/j.molimm.2010.01.007
  5. Rahnama M, Mahmoudi M, Zamani Taghizadeh Rabe S, Balali-Mood M, Karimi G, Tabasi N, et al. Evaluation of anti-cancer and immunomodulatory effects of carnosol in a Balb/c WEHI-164 fibrosarcoma model. J Immunotoxicol. 2015;12(3):231-8. https://doi.org/10.3109/1547691X.2014.934975
  6. Hasani-Ranjbar S, Larijani B, Abdollahi M. A systematic review of the potential herbal sources of future drugs effective in oxidant-related diseases. Infamma Allergy Drug Targets. 2009;8(1):2-10. https://doi.org/10.2174/187152809787582561
  7. Elyasi S, Shojaee FSR, Allahyari A, Karimi G. Topical Silymarin Administration for Prevention of Capecit-abine-Induced Hand-Foot Syndrome: A Randomized, Double‐Blinded, Placebo‐Controlled Clinical Trial. Phytother Res. 2017;31(9):1323-9. https://doi.org/10.1002/ptr.5857
  8. Elyasi S, Hosseini S, Niazi Moghadam MR, Aledavood SA, Karimi G. Effect of Oral Silymarin Administration on Prevention of Radiotherapy Induced Mucositis: A Randomized, Double‐Blinded, Placebo‐Controlled Clinical Trial. Phytother Res. 2016;30(11):1879-85. https://doi.org/10.1002/ptr.5704
  9. Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. "Silymarin", a promising pharmacological agent for treatment of diseases. Iran J Basic Med Sci. 2011(4);14:308.
  10. Agarwal R, Agarwal C, Ichikawa H, Singh RP, Aggarwal BB. Anticancer potential of silymarin: from bench to bed side. Anticancer Res. 2006;26(6B):4457-98.
  11. Vargas-Mendoza N, Madrigal-Santillan E, Morales-Gonzalez A, Esquivel-Soto J, Esquivel- Chirino C, y Gonzalez-Rubio MG-L, et al. Hepatoprotective effect of silymarin. World J Hepatol. 2014;6(3):144. https://doi.org/10.4254/wjh.v6.i3.144
  12. Razavi BM, Karimi G. Protective effect of silymarin against chemical-induced cardiotoxicity. Iran J Basic Med Sci. 2016;19(9):916.
  13. Darvishi Khezri H, Salehifar E, Kosaryan M, Aliasgh-arian A, Jalali H, Hadian Amree A. Potential effects of silymarin and its flavonolignan components in patients with ‐-Talassemia major: a comprehensive review in 2015. Adv Pharmacol Sci. 2016;2016.
  14. Gharagozloo M, Velardi E, Bruscoli S, Agostini M, Di Sante M, Donato V, et al. Silymarin suppress CD4+ T cell activation and proliferation: Effects on NF-${\kappa}B$ activity and IL-2 production. Pharmacol Res. 2010;61(5):405-9. https://doi.org/10.1016/j.phrs.2009.12.017
  15. Morishima C, Shuhart MC, Wang CC, Paschal DM, Apodaca MC, Liu Y, et al. Silymarin inhibits in vitro T-cell proliferation and cytokine production in hepatitis C virus infection. Gastroenterol. 2010;138(2):671-81. e2. https://doi.org/10.1053/j.gastro.2009.09.021
  16. Johnson VJ, He Q, Osuchowski MF, Sharma RP. Physiological Responses of a Natural Antioxidant Flavonoid Mixture, Silymarin, in BALB/c Mice. Planta Med 2003;69(01):44-9. https://doi.org/10.1055/s-2003-37023
  17. Lee JS, Kim SG, Kim HK, Lee TH, Jeong YI, Lee CM, et al. Silibinin polarizes T1/T2 immune responses through the inhibition of immunostimulatory function of dendritic cells. J Cell Physiol. 2007;210(2):385-97. https://doi.org/10.1002/jcp.20852
  18. Vaid M, Prasad R, Singh T, Elmets CA, Xu H, Katiyar SK. Silymarin inhibits ultraviolet radiation-induced immune suppression through DNA repair-dependent activation of dendritic cells and stimulation of effector T cells. Biochem Pharmacol. 2013;85(8):1066-76. https://doi.org/10.1016/j.bcp.2013.01.026
  19. Mady FM, Essa H, El-Ammawi T, Abdelkader H, Hussein AK. Formulation and clinical evaluation of silymarin pluronic-lecithin organogels for treatment of atopic dermatitis. Drug Des Devel Ter. 2016;10:1101.
  20. Choi YH, Jin GY, Guo HS, Piao HM, chang Li L, Li GZ, et al. Silibinin attenuates allergic airway inflammation in mice. Biochem Biophys Res Commun. 2012;427(3):450-5. https://doi.org/10.1016/j.bbrc.2012.07.112
  21. Bakhshaee M, Jabbari F, Hoseini S, Farid R, Sadeghian MH, Rajati M, et al. Effect of silymarin in the treatment of allergic rhinitis. Otolaryngol Head Neck Surg. 2011;145(6):904-9. https://doi.org/10.1177/0194599811423504
  22. Luster MI, Dean JH, Germolec DR. Consensus work-shop on methods to evaluate developmental immunotoxicity. Environ health perspect. 2003;111(4):579. https://doi.org/10.1289/ehp.5860
  23. Riahi B, Rafatpanah H, Mahmoudi M, Memar B, Brook A, Tabasi N, et al. Immunotoxicity of paraquat after subacute exposure to mice. Food Chem Toxicol. 2010;48(6):1627-31. https://doi.org/10.1016/j.fct.2010.03.036
  24. Neishabouri EZ, Hassan Z, Azizi E, Ostad S. Evaluation of immunotoxicity induced by diazinon in C57bl/6 mice. Toxicology. 2004;196(3):173-9. https://doi.org/10.1016/j.tox.2003.08.012
  25. Sena LA, Li S, Jairaman A, Prakriya M, Ezponda T, Hildeman DA, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling. Immunity. 2013;38(2):225-36. https://doi.org/10.1016/j.immuni.2012.10.020
  26. Schieke SM, McCoy Jr JP, Finkel T. Coordination of mitochondrial bioenergetics with G1 phase cell cycle progression. Cell Cycle. 2008;7(12):1782-7. https://doi.org/10.4161/cc.7.12.6067
  27. Byun HO, Kim HY, Lim JJ, Seo YH, Yoon G. Mitochondrial dysfunction by complex II inhibition delays overall cell cycle progression via reactive oxygen species production. J Cell Biochem. 2008;104(5):1747-59. https://doi.org/10.1002/jcb.21741
  28. Keramati MR, Balali-Mood M, Mousavi SR, Sadeghi M, Riahi-Zanjani B. Biochemical and hematological findings of Khorasan veterans 23 years after sulfur mustard exposure. J Res Med Sci. 2013;18(10):855.
  29. Devadas S, Zaritskaya L, Rhee SG, Oberley L, Williams MS. Discrete generation of superoxide and hydrogen peroxide by T cell receptor stimulation. J Exp Med. 2002;195(1):59-70. https://doi.org/10.1084/jem.20010659
  30. Caroleo M, Rispoli V, Arbitrio M, Strongoli C, Rainaldi G, Rotiroti D, et al. Chronic administration of paraquat produces immunosuppression of T lymphocytes and astrocytosis in rats. Toxic Subst Mech. 1996;15(3):183-94.
  31. Annunziata M, Iorio M. The levels of glutathione and hemoglobin in sheep erythrocytes as a function of age. Ital J Anim Sci. 2004;3(3):283-6. https://doi.org/10.4081/ijas.2004.283
  32. Witko-Sarsat V, Nguyen AT, Descamps-Latscha B. Immunomodulatory role of phagocyte-derived chloramines involving lymphocyte glutathione. Mediators Inflamm. 1993;2(3):235-41. https://doi.org/10.1155/S0962935193000328
  33. Victor, V. M., Rocha, M. and De la Fuente, M. Immune cells: free radicals and antioxidants in sepsis. Int Immunopharmacol. 2004;4(3):327-47. https://doi.org/10.1016/j.intimp.2004.01.020
  34. Grifths HR. ROS as signalling molecules in T cells--evidence for abnormal redox signalling in the autoimmune disease, rheumatoid arthritis. Redox Rep. 2005;10(6):273-80. https://doi.org/10.1179/135100005X83680
  35. Mahmoudi M, Zamani Taghizadeh Rabe S, Bala-li-Mood M, Karimi G, Memar B, Rahnama M, et al. Immunotoxicity induced in mice by subacute exposure to berberine. J Immunotoxicol. 2016;13(2):255-62. https://doi.org/10.3109/1547691X.2015.1058306