Tetrandrine on the dynamic changes of cytokines and antifungal effect in mice with Candida albicans
SHI Jian-ping1, LI Shui-xiu2, ZHU Kun-ju2, ZHANG Ling-ling2, ZHANG Yi-shan2, ZHANG Hong2
1. Shenzhen Shajing Affiliated Hospital of Guangzhou Medical University, Shenzhen 518000, China; 2.The First Affiliated Hospital and Institute of Mycology, Jinan University, Guangzhou 510632, China
Abstract：To study the therapeutic effect of tetrandrine(TET) on the mice infected with Candida albicans. The mice with disseminated candidiasis were randomly divided into experimental group and control group, The serum level of the IFN-γ, IL-10, TGF-β1 and IL-17A were determined by ELISA and kidney IFN-γ, IL-10, TGF-β1 and IL-17A mRNA expression levels were tested with real-time RT-PCR method. At the same time, kidmey fungal burdens were measured. Results showed that therapy with TET ranging from 15 to 45 mg/kg did not affect organ fungal burdens and survival times (P>0.05), and has nothing with the cellular immunity. However, 90 mg/kg of TET decreased organ fungal burdens and prolonged survival times, and correlated with increasing levels of cytokines of IFN-γ and TGF-β1, decreasing levels of IL-17A and IL-10 when observed in mice infected with SC5 314 compared with control group on day 8 after infection. Thus, 90 mg/kg of TET has therapeutic effects on disseminated candidiasis of mice.
石建萍, 李水秀, 朱坤举, 张玲玲, 张艺山, 张宏. 汉防己甲素对系统性白念珠菌感染小鼠的治疗作用[J]. 中国人兽共患病学报, 2016, 32(8): 689-696.
SHI Jian-ping, LI Shui-xiu, ZHU Kun-ju, ZHANG Ling-ling, ZHANG Yi-shan, ZHANG Hong. Tetrandrine on the dynamic changes of cytokines and antifungal effect in mice with Candida albicans. Chinese Journal of Zoonoses, 2016, 32(8): 689-696.
[1] Thakur JK, Arthanari H, Yang F, et al. A nuclear receptor-like pathway regulating multidrug resistance in fungi [J]. Nature, 2008,452(7187):604-609.doi:10.1038/nature06836. [2] Rebecca A, Drummond, Wallace C,et al. Cutting edge: failure of antigen-specific CD4 + T cell recruitment to the kidney during systemic candidiasis [J]. J Immunol, 2014,193(11):5381-5385.doi:10.4049/jimmunol.1401675. Epub 2014 Oct 24 [3] Kim J,Han BJ,Kim H,et al.Th1 immunity induction by ginsenoside Re involves in protection of mice against disseminated candidiasisdue to Candida albicans [J]. Int Immunopharmacol, 2012,14(4):481-486.doi:10.1016/j.intimp.2012.08.014. Epub 2012 Aug 29 [4] Lu JJ, Bao JL, Chen XP, et al. Alkaloids isolated from natural herbs as the anticancer agents [J]. Evid Based Complement Alternat Med,2012,2012:485042.doi:10.1155/2012/485042. Epub 2012 Sep 4 [5] Lai JH, Ho LJ, Lu KC, et al. Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspase cascades and is independent of Fas/Fas ligand Interaction [J]. J Immunol, 2001, 166 (11):6914-6924. [6] Jang BC, Lim KJ, Paik JH, et al. Tetrandrine-induced apoptosis is mediated by activation of caspases and PKCdelta in U937 cells [J]. Biochem Pharmacol, 2004, 67(10):1819-1829. [7] Zhang H, Gao AL, Li FX, et al. Mechanism of action of tetrandrine,a natural inhibitor of Candida albicans drug efflux Pumps [J].Yakugaku Zasshi, 2009, 129(5):623-630. [8] Guo H, Xie SM, Li SX, et al. Synergistic mechanism for tetrandrine on fluconazole against Candida albicans through the mitochondrial aerobic respiratory metabolism pathway[J]. J Med Microbiol. 2014,63(7):988-96.doi:10.1099/jmm.0.073890-0. Epub 2014 May 1 [9] Gao LQ, Zhang H, Zhang XL, et al. Differential proteomic analysis of fluconazole-sensitive Candida albicans before and after tetrandrine treatment[J].Chin Dermatol,2011, 44(8):560-563.(in Chinese) 高来强, 张宏, 张晓利, 等. 白念珠菌经汉防己甲素作用前后的差异蛋白质组学分析[J].中华皮肤科杂志, 2011, 44(8):560-563. [10] Wang KL, Zhang H, Jiang HH, et al. In vitro study on tetrandrine as a synergist to fluconazole in murine model of vaginal candidiasis[J]. Chin J Zoonoses, 2007, 23(5): 474-478,483. (in Chinese) 王凯丽,张宏,姜红浩,等. 汉防己甲素对氟康唑抗白念珠菌活性的增效作用的体内实验研究[J]. 中国人兽共患病学报,2007,23(5):474-478,483. [11] Zhang X,Guo H,Gao L,et al. Molecular mechanisms underlying the tetrandrine-mediated reversal of the fluconazole resistance of Candida albicans [J]. Pharm Biol,2013,51(6):749-752.doi:10.3109/13880209.2013.764537. Epub 2013 Mar 25. [12] Zhang XL,Zhang GH,Wang ZY,et al. Proteomic analysis reveals that Adh1p is involved in a synergistic fluconazole and tetrandrine mechanism against Candida albicans[J]. Pharmazie, 2013, 68(12):951-954. [13] Shi JP, Zhang H, Zhang ZD,et al. Clinical investigation on the synergistic effect of tetrandrine on the antifungal activity of fluconazole for vulvovaginal candidiasis[J]. Chin J Zoonoses,2009,25(11):1121-1123.(in Chinese) 石建平, 张宏, 张志东, 等.汉防己甲素对氟康唑外用治疗单纯性外阴阴道念珠菌病增效作用的临床研究[J].中国人兽共患病学报,2009,25(11):1121-1123. [14] Shi J, LI S, MA Z,et al.Acute and sub-chronic toxicity of tetrandrine in intravenously exposed female BALB/c Mice[J]. Chin J Integr Med,doi:10.1007/s11655-015-2303-2.2015,10.29 [15] He FQ, Qiu BY, Li TK, et al. Tetrandrine suppresses amyloid-β-induced inflammatory cytokines by inhibiting NF-κB pathway in murine BV2 microglial cells[J].Immunopharmacol, 2011,11(9):1220-1225.doi:10.1016/j.intimp.2011.03.023. Epub 2011 Apr 13 [16] Chen Y, Lai HS, Chiang BL, et al.Tetrandrine attenuates dendritic cell-mediated alloimmune responses and prolongs graft survival in mice[J].Lanta Med, 2010,76(13):1424-1430.doi:10.1055/s-0029-1240909. Epub 2010 Feb 25. [17] Fatahinia M,Khosravi AR,Shokri H. Propolis efficacy on TNF-α, IFN-γ and IL2 cytokines production in old mice with and without systemic candidiasis [J].J Mycol Med, 2012,22(3):237-242. doi:10.1016/j.mycmed.2012.05.004. Epub 2012 Aug 9 [18] Shimonkevitz R, Bar-Or D, Harris L, et al. Granulocytes, including neutrophils, synthesize IL-10 after traumatic pancreatitis:case report [J]. Trauma, 2000,48(1):165-168. [19] Hernández-Santos1 N and Gaffen SL.Th17 cells in immunity to Candida albicans [J].Cell Host Microbe. 2012,11(5): 425-435.doi:10.1016/j.chom.2012.04.008. [20] Whibley N, MacCallum DM, Vickers MA, et al. Expansion of Foxp3+ T-cell populations by Candida albicans enhances both Th17-cell responses and fungal dissemination after intravenous challenge[J].Eur J Immunol, 2014,44(4):1069-1083.doi:10.1002/eji.201343604. Epub 2014 Feb 13 [21] Mottet C, Uhlig H H, Powrie F. Cutting edge:cure of colitis by CD4 + CD25 + regulatory T cells [J]. Immunol, 2003,170:3939-3943. [22] Zhou L, Lopes JE, Chong MM, et al. TGF-beta-induced Foxp3 inhibitsT(H) 17 cell differentiation by antagonizing ROR gammat function [J]. Nature, 2008,453(7192):236-240. doi:10.1038/nature06878. Epub 2008 Mar 26
2016, Vol. 32 
