Abstract
Emodin, one of the major compounds in the herb Reynoutria elliptica, is known to maintain immunosuppressive, anti-allergic, anti-cancer, and anti-inflammatory effects. In this study, we assessed the possibility of using emodin to induce apoptosis in stimulated immune cells in vitro. After treatment with emodin and concanavalin A (Con A), we observed DNA damage-induced apoptosis in splenocytes. Moreover, treatment with emodin and Con A increased the number of apoptotic splenocytes compared with untreated controls. Emodin also diminished the size of CD45R/B220+ cells, CD19+CD69+ cells, and cDC populations. These results indicate that emodin-induced apoptosis was involved in attenuating the immune activity promoted by DNA damage and in decreasing the number of CD45R/B220+ B cells and CD19+CD69+ activating B cells. This demonstration of emodin inducing apoptosis of Con A-stimulated immune cells indicates its potential utility as a therapy for diseases caused by abnormally activated immune cells.
Keywords: emodin, apoptosis, autoimmune disease, concanavalin A, immune cells
References
- 1.Opferman JT, Korsmeyer SJ. Apoptosis in the development and maintenance of the immune system. Nat. Immunol. 2003;4:410–415. doi: 10.1038/ni0503-410. [DOI] [PubMed] [Google Scholar]
- 2.Schmied M, Breitschopf H, Gold R, Zischler H, Rothe G, Wekerle H, Lassmann H. Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am. J. Pathol. 1993;143:446–452. [PMC free article] [PubMed] [Google Scholar]
- 3.Pender MP. Activation-induced apoptosis of autoreactive and alloreactive T lymphocytes in the target organ as a major mechanism of tolerance. Immunol. Cell Biol. 1999;77:216–223. doi: 10.1046/j.1440-1711.1999.00818.x. [DOI] [PubMed] [Google Scholar]
- 4.Izhaki I. Emodin–a secondary metabolite with multiple ecological functions in higher plants. New Phytol. 2002;155:205–217. doi: 10.1046/j.1469-8137.2002.00459.x. [DOI] [Google Scholar]
- 5.Huang HC, Chang JH, Tung SF, Wu RT, Foegh ML, Chu SH. Immunosuppressive effect of emodin, a free radical generator. Eur. J. Pharmacol. 1992;211:359–364. doi: 10.1016/0014-2999(92)90393-I. [DOI] [PubMed] [Google Scholar]
- 6.Lin SZ, Chen KJ, Tong HF, Jing H, Li H, Zheng SS. Emodin attenuates acute rejection of liver allografts by inhibiting hepatocellular apoptosis and modulating the Th1/Th2 balance in rats. Clin. Exp. Pharmacol.^P. 2010;37:790–794. doi: 10.1111/j.1440-1681.2010.05378.x. [DOI] [PubMed] [Google Scholar]
- 7.Kim DH, Park EK, Bae EA, Han MJ. Metabolism of rhaponticin and chrysophanol 8-o-beta-D-glucopyranoside from the rhizome of rheum undulatum by human intestinal bacteria and their anti-allergic actions. Biol. Pharm. Bull. 2000;23:830–833. doi: 10.1248/bpb.23.830. [DOI] [PubMed] [Google Scholar]
- 8.Lu Y, Yang JH, Li X, Hwangbo K, Hwang SL, Taketomi Y, Murakami M, Chang YC, Kim CH, Son JK, Chang HW. Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation. Biochem. Pharmacol. 2011;82:1700–1708. doi: 10.1016/j.bcp.2011.08.022. [DOI] [PubMed] [Google Scholar]
- 9.Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P. Molecular mechanism of emodin action: Transition from laxative ingredient to an antitumor agent. Med. Res. Rev. 2007;27:591–608. doi: 10.1002/med.20095. [DOI] [PubMed] [Google Scholar]
- 10.Zhang L, Chang CJ, Bacus SS, Hung MC. Suppressed transformation and induced differentiation of HER-2/neu-overexpressing breast cancer cells by emodin. Cancer Res. 1995;55:3890–3896. [PubMed] [Google Scholar]
- 11.Zhang L, Hung MC. Sensitization of HER-2/neu-overexpressing non-small cell lung cancer cells to chemotherapeutic drugs by tyrosine kinase inhibitor emodin. Oncogene. 1996;12:571–576. [PubMed] [Google Scholar]
- 12.Kuo YC, Meng HC, Tsai WJ. Regulation of cell proliferation, inflammatory cytokine production and calcium mobilization in primary human T lymphocytes by emodin from Polygonum hypoleucum Ohwi. Inflamm. Res. 2001;50:73–82. doi: 10.1007/s000110050727. [DOI] [PubMed] [Google Scholar]
- 13.Meng G, Liu Y, Lou C, Yang H. Emodin suppresses lipopolysaccharide-induced pro-inflammatory responses and NF-κB activation by disrupting lipid rafts in CD14-negative endothelial cells. Brit. J. Pharmacol. 2010;161:1628–1644. doi: 10.1111/j.1476-5381.2010.00993.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Qu K, Shen N, Xu X, Su H, Wei J, Tai M, Meng F, Zhou L, Zhang Y, Liu C. Emodin induces human T cell apoptosis in vitro by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction. Acta Pharmacol. Sin. 2013;34:1217–1228. doi: 10.1038/aps.2013.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Cherng JM, Chiang W, Wang JH, Lin CM, Lee CY, Shih CM, Chiang LC. Anthraquinones of edible wild vegetable Cassia tora stimulate proliferation of human CD4+ T lymphocytes and secretion of interferon-gamma or interleukin 10. Food Chem. 2008;107:1576–1580. doi: 10.1016/j.foodchem.2007.10.005. [DOI] [Google Scholar]
- 16.Tong H, Chen K, Chen H, Wu H, Lin H, Ni Z, Lin S. Emodin prolongs recipient survival time after orthotopic liver transplantation in rats by polarizing the Th1/Th2 paradigm to Th2. Anat. Rec. 2011;294:445–452. doi: 10.1002/ar.21352. [DOI] [PubMed] [Google Scholar]
- 17.Hong J, Gu X, Xiang J, Zhang Z, Zang Y, Zhang Q, Qian S, Chen Z. Recipient dendritic cells modified by RNA interference targeting CD80 and CD86 elicit T cell hyporesponsiveness via enhanced T cell apoptosis. Chinese Med. J.-Pecking. 2013;126:2139–2144. [PubMed] [Google Scholar]
- 18.Karthaus N, Hontelez S, Looman MWG, van Spriel AB, Ansems M, Adema GJ. Nuclear receptor expression patterns in murine plasmacytoid and conventional dendritic cells. Mol. Immunol. 2013;55:409–417. doi: 10.1016/j.molimm.2013.03.020. [DOI] [PubMed] [Google Scholar]
- 19.Lu Y, Jeong YT, Li X, Kim MJ, Park PH, Hwang SL, Son JK, Chang HW. Emodin isolated from Polygoni cuspidati radix inhibits TNF-α and IL-6 release by blockading NF-κB and MAP kinase pathways in mast cells stimulated with PMA Plus A23187. Biomol. Ther. 2013;21:435–441. doi: 10.4062/biomolther.2013.068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Kang KA, Zhang R, Piao MJ, Lee KH, Kim BJ, Kim SY, Kim HS, Kim DH, You HJ, Hyun JW. Inhibitory effects of glycitein on hydrogen peroxide induced cell damage by scavenging reactive oxygen species and inhibiting c-Jun N-terminal kinase. Free Radical Res. 2007;41:720–729. doi: 10.1080/10715760701241618. [DOI] [PubMed] [Google Scholar]
- 21.Manh TPV, Alexandre Y, Baranek T, Crozat K, Dalod M. Plasmacytoid, conventional, and monocyte-derived dendritic cells undergo a profound and convergent genetic reprogramming during their maturation. Eur. J. Immunol. 2013;43:1706–1715. doi: 10.1002/eji.201243106. [DOI] [PMC free article] [PubMed] [Google Scholar]
