Immunoregulatory effects of Tripterygium wilfordii Hook F and its extracts in clinical practice

Abstract

Tripterygium wilfordii Hook F (TwHF) and its extracts have long been used for the treatment of rheumatoid arthritis, autoimmune diseases, and kidney disease due to their anti-inflammatory, immunoregulatory, and other pharmacological effects. However, the clinical immunoregulatory effects of TwHF and its extracts remain unclear, so we reviewed their effects for use in clinical practice. This review provides a comprehensive summary of the recent literature on the immunoregulatory effects of TwHF and its extracts in clinical studies. TwHF and its extracts affect the proliferation and activation of T and B cells; ratio of T cell subsets; inflammatory response of monocytes, macrophages, and immunoglobulins; and secretion of many cytokines. Together, these effects dictate immune function in a variety of diseases. TwHF and its extracts can be used alone or in combination with existing therapies against many immune disorders through immunomodulation.

Keywords

Tripterygium wilfordii Hook F / immunoregulation / clinical studies

References

[1] Wang X, Zu Y, Huang L, Yu J, Zhao H, Wen C, Chen Z, Xu Z. Treatment of rheumatoid arthritis with combination of methotrexate and Tripterygium wilfordii: a meta-analysis. Life Sci 2017; 171: 45–50

[2] Patavino T, Brady DM. Natural medicine and nutritional therapy as an alternative treatment in systemic lupus erythematosus. Altern Med Rev 2001; 6(5): 460–471

[3] Mao SJ, Huang XM. Tripterygium wilfordii Hook F is efficacious in the treatment of Henoch-Schönlein purpura nephritis in children. World J Pediatr 2016; 12(3): 375–376

[4] Zhang C, Sun PP, Guo HT, Liu Y, Li J, He XJ, Lu AP. Corrigendum: Safety profiles of Tripterygium wilfordii Hook F: a systematic review and meta-analysis. Front Pharmacol 2017; 8: 59

[5] Chen F, Ma YL, Ding H, Chen BP. Effects of Tripterygium wilfordii glycosides on regulatory T cells and Th17 in an IgA nephropathy rat model. Genet Mol Res 2015; 14(4): 14900–14907

[6] Chen P, Han R, Zhou Q, Cheng H, Zhu K. Modulatory effect of triptolide on differentiation of human Th17 cells. Chin J Chin Mater Med (Zhongguo Zhong Yao Za Zhi) 2011; 36(11): 1499–1502 (in Chinese)

[7] Yan YH, Shang PZ, Lu QJ, Wu X. Triptolide regulates T cell-mediated immunity via induction of CD11c^low dendritic cell differentiation. Food Chem Toxicol 2012; 50(7): 2560–2564

[8] Tao X, Davis LS, Lipsky PE. Effect of an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F on human immune responsiveness. Arthritis Rheum 1991; 34(10): 1274–1281

[9] Brinker AM, Ma J, Lipsky PE, Raskin I. Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae). Phytochemistry 2007; 68(6): 732–766

[10] Zhou Y, Hong Y, Huang H. Triptolide attenuates inflammatory response in membranous glomerulo-nephritis rat via downregulation of NF-kB signaling pathway. Kidney Blood Press Res 2016; 41(6): 901–910

[11] Abdin AA, Hasby EA. Modulatory effect of celastrol on Th1/Th2 cytokines profile, TLR2 and CD3⁺ T-lymphocyte expression in a relapsing-remitting model of multiple sclerosis in rats. Eur J Pharmacol 2014; 742: 102–112

[12] Li RL, Liu PL, Wu XC. Clinical and experimental study on sustained release tablet of Tripterygium wilfordii in treating rheumatoid arthritis. Chin J Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 1996; 16(1): 10–13 (in Chinese)

[13] Li LL. Effects of Tripterygium wilfordii polyglycoside on plasma TNF-α and IL-6 in patients with rheumatoid arthritis. Acta Acad Med Guangxi (Guangxi Yi Ke Da Xue Xue Bao) 2005; 22(5): 33–35 (in Chinese)

[14] Goldbach-Mansky R, Wilson M, Fleischmann R, Olsen N, Silverfield J, Kempf P, Kivitz A, Sherrer Y, Pucino F, Csako G, Costello R, Pham TH, Snyder C, van der Heijde D, Tao X, Wesley R, Lipsky PE. Comparison of Tripterygium wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis: a randomized trial. Ann Intern Med 2009; 151(4): 229–240, W49–51

[15] Min J, Jing YP, Gu ZH. Effects of Tripterygium wilfordii polyglycoside combined with leflunomide on elderly rheumatoid arthritis and interleukin-1, interleukin-6 and tumor necrosis factor-α. Pharmacol Clin Chin Mater Clin Med (Zhong Yao Yao Li Yu Lin Chuang) 2013; 29(3): 185–186 (in Chinese)

[16] Cui YX, Yang L. Effects of Tripterygium wilfordii polyglycoside combined with leflunomide on C-reactive protein, interleukin-10, soluble cell adhesion molecule 1 levels of elderly patients with active rheumatoid arthritis. Chin J Gerontol (Zhongguo Lao Nian Xue Za zhi) 2016; 36(19): 4878–4880 (in Chinese)

[17] Li YJ, Zhang T, Zhu XF, Tu JX, Jin Y, Xia XR. Clinical analysis of Tripterygium wilfordii polyglycoside combined with tocilizumab in the treatment of rheumatoid arthritis. Chin Med Mat (Zhong Yao Cai) 2015; 38(8): 1775–1777 (in Chinese)

[18] Peng AP, Wang XY, Zhuang JH. Effect of triptolide on COX2/PGE2 axis to inhibit Th17 cell differentiation. Chin J Chin Mater Med (Zhongguo Zhong Yao Za Zhi) 2014, 39(3): 536–539 (in Chinese)

[19] Elmesmari A, Fraser AR, Wood C, Gilchrist D, Vaughan D, Stewart L, McSharry C, McInnes IB, Kurowska-Stolarska M. MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in rheumatoid arthritis. Rheumatology (Oxford) 2016; 55(11): 2056–2065

[20] Peng A, Huang X, Liu R, Wang X, Zhuang J. Triptolide inhibits the inflammatory response of monocytes from rheumatoid arthritis patients by regulating miR-155. Cell Mol Immunol (Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi) 2014; 30(6): 635–638 (in Chinese)

[21] Yang Y, Ye Y, Qiu Q, Xiao Y, Huang M, Shi M, Liang L, Yang X, Xu H. Triptolide inhibits the migration and invasion of rheumatoid fibroblast-like synoviocytes by blocking the activation of the JNK MAPK pathway. Int Immunopharmacol 2016; 41: 8–16

[22] Yu Y, Koehn CD, Yue Y, Li S, Thiele GM, Hearth-Holmes MP, Mikuls TR, O’Dell JR, Klassen LW, Zhang Z, Su K. Celastrol inhibits inflammatory stimuli-induced neutrophil extracellular trap formation. Curr Mol Med 2015; 15(4): 401–410

[23] Yang MH, Wu FX, Xie CM, Qing YF, Wang GR, Guo XL, Tang Z, Zhou JG, Yuan GH. Expression of CC chemokine ligand 5 in patients with rheumatoid arthritis and its correlation with disease activity and medication. Chin Med Sci J 2009; 24(1): 50–54

[24] Li W, Wang X, Li J, Liu M, Feng J. A study of immunocyte subsets and serum cytokine profiles before and after immunal suppression treatment in patients with immune thrombocytopenia. Chin J Intern Med (Zhonghua Nei Ke Za Zhi) 2016; 55(2): 111–115 (in Chinese)

[25] Yu XQ, Chen HM, Sun JH, Luo M, Lu YL. Therapeutic efficacy of multigly-cosidorum Tripterygium combined with rhIL-11 for immune thrombocytopenia. J Exp Hematol (Zhongguo Shi Yan Xue Ye Xue Za Zhi) 2015; 23(5): 1400–1403 (in Chinese)

[26] Shen J, Li Z, Li W, Ge Y, Xie M, Lv M, Fan Y, Chen Z, Zhao D, Han Y. Th1, Th2, and Th17 cytokine involvement in thyroid associated ophthalmopathy. Dis Markers 2015; 2015: 609593

[27] Xu JP, Xu JP, Xu C, Chen J, Jin ZH, Zheng HF, Zhu J. Peripheral blood cell factors of Graves ophthalmopathy and effect of intervention with Tripterygium glycosides. Chin J Chin Mater Med (Zhongguo Zhong Yao Za Zhi) 2014; 39(3): 544–547 (in Chinese)

[28] Yan SX, Wang Y. Inhibitory effects of triptolide on interferon-γ-induced human leucocyte antigen-DR, intercellular adhesion molecule-1, CD40 expression on retro-ocular fibroblasts derived from patients with Graves’ ophthalmopathy. Clin Experiment Ophthalmol 2006; 34(3): 265–271

[29] Huang QS, Zhang ZL, Liu YM. Effect of Tripterygium wilfordii polyglycoside on serum IL-2 and TNF-α in patients with acute anterior U-veitis. Chin J Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 2002; 22(6): 432–434 (in Chinese)

[30] Li G, Ren J, Wang G, Gu G, Hu D, Ren H, Hong Z, Wu X, Liu S, Li J. T2 enhances in situ level of Foxp3⁺ regulatory cells and modulates inflammatory cytokines in Crohn’s disease. Int Immunopharmacol 2014; 18(2): 244–248

[31] Ren J, Tao Q, Wang X, Wang Z, Li J. Efficacy of T2 in active Crohn’s disease: a prospective study report. Dig Dis Sci 2007; 52(8): 1790–1797

[32] Li ZX, Tan H, Xiong XJ. Clinical effect of Tripterygiitotorum combined with prednisone and its effect on serum IL-6 level in treating patients with myasthenia gravis. Chin J Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 2002; 22(3): 175–177 (in Chinese)

[33] Wang XH, Zhang ZY. Effect of Tripterygium polyglucoside on T-lymphocyte subsets and serum interleukin-5 level in asthma patients. Chin J Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 2001; 21(1): 25–27 (in Chinese)

[34] Lin KX, Wang CZ, Qian GS. Effect of Tripterygium wilfordii on Th1, Th2 cytokines production in asthma patients. Chin J Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 2001; 21(1): 22–24 (in Chinese)

[35] Xu JY, Jiang FX, Qiu YJ. Effects of Tripterygium polyglucosideo (TP) on cytokines and eosinophil apoptosis in asthmatic patients in sputum. Chin J Microbiol Immunol (Zhong hua Wei Sheng Wu Xue He Mian Yi Xue Za Zhi) 2004; 24(2): 57–59 (in Chinese)

[36] Shen QJ, Wang LM, Wang JH, Xu YP, Zhu LJ. Modulatory effect of glucosidorum Tripterygii tororum (GTT) on TH1/TH2 cytokine balance state of asthmatic patients. Chin J Microbiol Immunol (Zhong hua Wei Sheng Wu Xue He Mian Yi Xue Za Zhi) 2002; 22(3): 96–98 (in Chinese)

[37] Zhang X, Xia J, Ye H. Effect of Tripterygium polyglycoside on interleukin-6 in patients with Guillain-Barre syndrome. Chin J Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 2000; 20(5): 332–334(in Chinese)

[38] Zhang X, Xia JH, Ye HH. Effect of Tripterygium wilfordii polyglycoside on IL-6 and sIL-2R in serum and cerebrospinal fluid of patients with Guillain-Barré syndrome. Chin J Immunol (Zhongguo Mian Yi Xue Za Zhi) 2001; 17(1): 53–54 (in Chinese)

[39] Zhang XZ, Li S, Wu XZ. Effects of Tripterygiitotorum in the treatment of insulin dependent diabetes mellitus with islet transplantation. Chin J Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 1994; 14(8): 451–453 (in Chinese)

[40] Ji W, Chen Y, Zhao X, Guo Y, Zhong L, Li H, Wang D, Song Y. Beneficial effects of Tripterygium glycosides tablet on biomarkers in patients with ankylosing spondylitis. Mol Med Rep 2015; 12(1): 684–690

[41] Ji W, Li H, Gao F, Chen Y, Zhong L, Wang D. Effects of Tripterygium glycosides on interleukin-17 and CD4⁺CD25⁺ CD127^low regulatory T-cell expression in the peripheral blood of patients with ankylosing spondylitis. Biomed Rep 2014; 2(4): 517–520

[42] Lan SH, Ye J, Zou X, Wang HZ, Zhao LJ. Effect of Tripterygium wilfordii on serum levels of IL-6, IL-17 and IL-23 in patients with psoriasis vulgaris. J Clin Dermatol (Lin Chuang Pi Fu Ke Za Zhi) 2017; 46(12): 877–879 (in Chinese)

[43] Li T, Xie J, Li Y, Routy JP, Li Y, Han Y, Qiu Z, Lv W, Song X, Sun M, Zhang X, Wang F, Jiang H. Tripterygium wilfordii Hook F extract in cART-treated HIV patients with poor immune response: a pilot study to assess its immunomodulatory effects and safety. HIV Clin Trials 2015; 16(2): 49–56

[44] Peng XB, Wang N, Zeng K. Effect of Tripterygium wilforddi Hook on the expression of nuclear factor-kB in peripheral blood mononuclear cells in patients with systemic lupus erythematosus. Chin J Derm Venereol (Zhongguo Pi Fu Xing Bing Xue Za Zhi) 2006; 20(6): 336–337 (in Chinese)

[45] Jin CY, Hu GH, Zheng BZ, Wang DL. Study on effect of Tripterygium on plasma IL-18 content in patients with lupus nephritis. Chin J Chin Mater Med (Zhongguo Zhong Yao Za Zhi) 2008; 33(9): 1075–1077 (in Chinese)

[46] Song HX, Gong J, Chen W. Effect of triptolide on urinary monocyte chemoattractant protein-1 in patients with diabetic nephropathy. Chin J Integr Tradit West Med (Zhongguo Zhong Xi Yi Jie He Za Zhi) 2005; 25(5): 416–418 (in Chinese)

[47] Ma R, Xu Y, Jiang W, Zhang W. Combination of Tripterygium wilfordii Hook F and angiotensin receptor blocker synergistically reduces excretion of urinary podocytes in patients with type 2 diabetic kidney disease. Biotechnol Biotechnol Equip 2015; 29(1): 139–146

[48] Xu GB, Chen DJ, Chen WZ. Effect of Tripterygium wilfordii polyglycoside on inflammatory factor level in patients with diabetic nephropathy. Chin Arch J Tradit Chin Med (Zhonghua Zhong Yi Yao Xue Kan) 2017; 35(8): 2206–2208 (in Chinese)

[49] Hu GH, Yi ZW, Wang JH, Yao JC. Effect of Triptergium wilfordii polyglycosidium on content of Th1 and Th2 in child recurrent nephrotic syndrome. Chin J Chin Mater Med (Zhongguo Zhong Yao Za Zhi) 2008; 33(4): 441–443 (in Chinese)

[50] Pei WY, Yang CH, Zhang XL. Effects and mechanism of Tripterygium wilfordii on chronic glomerulo nephritis. Genet Mol Res 2016; 15(1): 1–7

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81673844, 81573845, 81373773, and 81760838), the Beijing Natural Science Foundation (No. 7142144), China Scholarship Council Fund (No. 201609110029), the International Cooperation Project of the State Administration of Traditional Chinese Medicine (No. GZYYGJ2017014), and the International Cooperation Project of the Ministry of Science and Technology (No. 2014DFA31490).

Compliance with ethics guidelines

Dan Luo, Zhengyun Zuo, Hongyan Zhao, Yong Tan, and Cheng Xiao declare that they have no financial conflicts of interest. This manuscript is a review article and does not involve a research protocol requiring approval by a relevant institutional review board or ethics committee.

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