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http://dx.doi.org/10.3831/KPI.2018.21.011

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)
Publication Information
Journal of Pharmacopuncture / v.21, no.2, 2018 , pp. 90-97 More about this Journal
Abstract
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.
Keywords
Silymarin; Immunomodulatory; Cellular immunity; Humoral immunity;
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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.   DOI
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.   DOI
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.   DOI
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.   DOI
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.   DOI
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.   DOI
8 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.
9 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.   DOI
10 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.
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.   DOI
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.   DOI
15 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.   DOI
16 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.   DOI
17 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.   DOI
18 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.   DOI
19 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.   DOI
20 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.
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.   DOI
22 Luster MI, Dean JH, Germolec DR. Consensus work-shop on methods to evaluate developmental immunotoxicity. Environ health perspect. 2003;111(4):579.   DOI
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.   DOI
24 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.   DOI
25 Neishabouri EZ, Hassan Z, Azizi E, Ostad S. Evaluation of immunotoxicity induced by diazinon in C57bl/6 mice. Toxicology. 2004;196(3):173-9.   DOI
26 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.   DOI
27 Schieke SM, McCoy Jr JP, Finkel T. Coordination of mitochondrial bioenergetics with G1 phase cell cycle progression. Cell Cycle. 2008;7(12):1782-7.   DOI
28 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.   DOI
29 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.
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.   DOI
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.   DOI
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.   DOI
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.   DOI
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.   DOI