Abstract
Tripterygium wilfordii Hook F has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and kidney disease, especially in traditional Chinese medicine. The mechanisms underlying its effects may be diverse but they remain unclear, and its toxicity and side effects limit its wider clinical application. This review summarizes the clinical application of Tripterygium wilfordii Hook F in recent years, as well as the results of studies into its mechanisms and toxicity, to provide a reference for its future clinical application.
概 要
雷公藤作为中国传统药材的瑰宝, 具有较强的抗炎及免疫抑制作用, 临床上广泛应用于类风湿性关节炎、 系统性红斑狼疮、 肾脏疾病等自身免疫性及炎症性疾病. 由于雷公藤对于自身免疫疾病疗效显著, 且没有激素的副作用, 近年来备受国内外研究者关注, 大量研究开始探究其抗炎及免疫抑制的潜在机制. 而雷公藤本身也存在毒副作用, 限制了其在临床更广泛的应用. 本文总结了近年来雷公藤在免疫相关炎性疾病临床应用情况, 雷公藤抗炎和免疫调节的机制以及目前雷公藤减毒的方法, 旨在更好地帮助临床医生及科研工作者理解雷公藤的生物特性及作用机制, 为临床应用及推广提供参考依据.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Boorsma CE, Draijer C, Melgert BN, 2013. Macrophage heterogeneity in respiratory diseases. Mediators Inflamm, 2013:769214. https://doi.org/10.1155/2013/769214
Cao LJ, Yan M, Li HD, et al., 2015. Progress on mechanism of Tripterygium wilfordii-induced liver injury and detoxification mechanism of licorice. China J Chin Mat Med, 40(13):2537–2541 (in Chinese). https://doi.org/10.4268/cjcmm20151310
Chen H, Cao F, Li X, et al., 2015. Clinical effect of mycophenolate mofetil and tripterygium glycosides on refractory nephrotic syndrome and the influence of renal function. Chin J Diffic Compl Cases, 14(4):363–365 (in Chinese). https://doi.org/10.3969/j.issn.1671-6450.2015.04.010
Chen QX, 2015. Effects of different processing methods on the toxic components of Tripterygium wilfordii. Chin J Clin Rational Drug Use, (29):103–104 (in Chinese). https://doi.org/10.15887/j.cnki.13-1389/r.2015.29.067
Chen X, Murakami T, Oppenheim JJ, et al., 2005. Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking. Blood, 106(7):2409–2416. https://doi.org/10.1182/blood-2005-03-0854
Du JL, Cui MH, Su ZW, et al., 2008. Effects of compatibility of Tripterygium wilfordii Hook and licorice on biochemical indexes in rats. J Pract Tradit Chin Int Med, 22(5):71–72 (in Chinese). https://doi.org/10.3969/j.issn.1671-7813.2008.05.060
Feng MX, Li YN, Ruan WS, et al., 2018. Predictive value of the maximum serum creatinine value and growth rate in acute paraquat poisoning patients. Sci Rep, 8(1):11587. https://doi.org/10.1038/s41598-018-29800-0
Gao S, Wake H, Gao Y, et al., 2019. Histidine-rich glycoprotein ameliorates endothelial barrier dysfunction through regulation of NF-κB and MAPK signal pathway. Br J Pharmacol, 176(15):2808–2824. https://doi.org/10.1111/bph.14711
Gu YW, Chen JS, Yang M, et al., 2018. Research advances in preparations of Tripterygium wilfordii for external use. Pharm Care Res, 18(1):33–37 (in Chinese). https://doi.org/10.5428/pcar20180109
Han R, Rostami-Yazdi M, Gerdes S, et al., 2012. Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases. Br J Clin Pharmacol, 74(3):424–436. https://doi.org/10.1111/j.1365-2125.2012.04221.x
He YM, Yao YY, Chen YL, et al., 2017. Research progress of Tripterygium wilfordii preparations. China Pharm, 28(4): 551–554 (in Chinese). https://doi.org/10.6039/j.issn.1001-0408.2017.04.33
Hong YZ, Zhou WD, Li K, et al., 2002. Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells. Kidney Int, 62(4): 1291–1300. https://doi.org/10.1111/j.1523-1755.2002.kid586.x
Hu PY, Li ZL, Pu SB, et al., 2013. Research advances on Triptreygium wilfordii. Chin Wild Plant Resour, 32(2):1–3 (in Chinese). https://doi.org/10.3969/j.issn.1006-9690.2013.02.001
Ji SM, Wang QW, Yin G, et al., 2007. Outcome of 5 years of immunosuppression with Tripterygium wilfordii Hook F in renal allograft transplant recipients. J Med Postgr, 20(1):53–57 (in Chinese). https://doi.org/10.3969/j.issn.1008-8199.2007.01.015
Jiang M, Liu XH, Zhang DH, et al., 2018. Celastrol treatment protects against acute ischemic stroke-induced brain injury by promoting an IL-33/ST2 axis-mediated microglia/macrophage M2 polarization. J Neuroinflammation, 15(1):78. https://doi.org/10.1186/s12974-018-1124-6
Lamkanfi M, Dixit VM, 2014. Mechanisms and functions of inflammasomes. Cell, 157(5):1013–1022. https://doi.org/10.1016/j.cell.2014.04.007
Lee S, Vasudevan S, 2013. Post-transcriptional stimulation of gene expression by microRNAs. In: Chan EKL, Fritzler MJ (Eds.), Ten Years of Progress in GW/P Body Research. Springer, New York, p.97–126. https://doi.org/10.1007/978-1-4614-5107-5_7
Li GW, Ren JA, Wang GF, et al., 2014. T2 enhances in situ level of Foxp3+ regulatory cells and modulates inflammatory cytokines in Crohn’s disease. Int Immunopharmacol, 18(2):244–248. https://doi.org/10.1016/j.intimp.2013.12.014
Li H, Liu ZH, Dai CS, et al., 2002. Triptolide inhibits proinflammatory factor-induced over-expression of class II MHC and B7 molecules in renal tubular epithelial cells. Acta Pharmacol Sin, 23(9):775–781.
Li J, Shen FH, Guan CW, et al., 2014. Activation of Nrf2 protects against triptolide-induced hepatotoxicity. PLoS ONE, 9(7):e100685. https://doi.org/10.1371/journal.pone.0100685
Li Y, Yu C, Zhu WM, et al., 2010. Triptolide ameliorates IL-10-deficient mice colitis by mechanisms involving suppression of IL-6/STAT3 signaling pathway and down-regulation of IL-17. Mol Immunol, 47(15):2467–2474. https://doi.org/10.1016/j.molimm.2010.06.007
Li Y, Tian Y, Zhu WM, et al., 2013. Triptolide induces suppressor of cytokine signaling-3 expression and promotes lamina propria mononuclear cells apoptosis in Crohn’s colitis. Int Immunopharmacol, 16(2):268–274. https://doi.org/10.1016/j.intimp.2013.04.018
Li YS, Tong PJ, Ma HZ, et al., 2006. Toxicity attenuation and efficacy potentiation effect of liquorice on treatment of rheumatoid arthritis with Tripterygium wilfordii. Chin J Integr Tradit West Med, 26(12):1117–1119 (in Chinese). https://doi.org/10.3321/j.issn:1003-5370.2006.12.013
Liang Y, Zhang XL, Liu B, et al., 2019. Curative effect of tripterygium glycosides combined with irbesartan on IgA nephropathy with increased urinary podocyte excretion. Chin Gen Pract, 22(12):1426–1431 (in Chinese). https://doi.org/10.12114/jissn.1007-9572.2018.00.403
Liao NS, Ren JA, Fan CG, et al., 2009. Efficacy of polyglycosides of Tripterygium wilfordii in preventing postoperative recurrence of crohn disease. Chin J Gastrointest Surg, 12(2):167–169 (in Chinese). https://doi.org/10.3760/cma.jissn.1671-0274.2009.02.025
Lichtenstein GR, Rutgeerts P, Sandborn WJ, et al., 2012. A pooled analysis of infections, malignancy, and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease. Am J Gastroenterol, 107(7):1051–1063. https://doi.org/10.1038/ajg.2012.89
Liu Q, Chen T, Chen G, et al., 2007. Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2 expression through PI3-K/Akt and NF-κB pathways. Mol Immunol, 44(10):2686–2696. https://doi.org/10.1016/j.molimm.2006.12.003
Liu QY, Chen TY, Chen HB, et al., 2004. Triptolide (PG-490) induces apoptosis of dendritic cells through sequential p38 MAP kinase phosphorylation and caspase 3 activation. Biochem Biophys Res Commun, 319(3):980–986. https://doi.org/10.1016/j.bbrc.2004.04.201
Liu W, Yan L, Zhu Q, et al., 2014. Therapeutic effect of tripterygium glycosides plus prednisone on moderate active systemic lupus erythematosus. J Chin Pract Diagn Ther, 28(12):1234–1235 (in Chinese). https://doi.org/10.13507/j.issn.1674-3474.2014.12.038
Lu YQ, 2018. HIV and paraquat poisoning: fighting fire with fire? J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(2): 168–170. https://doi.org/10.1631/jzus.b1700567
Luo D, Guo YM, Cheng Y, et al., 2017. Natural product celastrol suppressed macrophage M1 polarization against inflammation in diet-induced obese mice via regulating Nrf2/HO-1, MAP kinase and NF-kB pathways. Aging (Albany NY), 9(10):2069–2082. https://doi.org/10.18632/aging.101302
Lv M, Deng JW, Tang N, et al., 2018. Efficacy and safety of Tripterygium wilfordii Hook F on psoriasis vulgaris: a systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med, 2018: 2623085. https://doi.org/10.1155/2018/2623085
Lv QW, Zhang W, Shi Q, et al., 2015. Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial. Ann Rheum Dis, 74(6): 1078–1086. https://doi.org/10.1136/annrheumdis-2013-204807
Ma Z, Zhang Y, Liang MX, 2014. Toxicity reducing and efficacy enhancing research on rheumatoid arthritis effect of tripterygium compatible with licorice. Asia Pac Tradit Med, 10(8):9–11 (in Chinese).
Ma ZJ, Dong JM, Wang JB, et al., 2017. Compatibility attenuated research of Glycyrrhiza concocted Tripterygium wilfordii based on high content analysis. Mod Chin Med, 19(11):1562–1565 (in Chinese). https://doi.org/10.13313/j.issn.1673-4890.2017.11.013
Mei ZN, Li XK, Wu QR, et al., 2005. The research on the anti-inflammatory activity and hepatotoxicity of triptolide-loaded solid lipid nanoparticle. Pharmacol Res, 51(4): 345–351. https://doi.org/10.1016/j.phrs.2004.10.007
Middleton J, Americh L, Gayon R, et al., 2004. Endothelial cell phenotypes in the rheumatoid synovium: activated, angiogenic, apoptotic and leaky. Arthritis Res Ther, 6(2): 60–72. https://doi.org/10.1186/ar1156
Murray PJ, 2017. Macrophage polarization. Annu Rev Physiol, 79:541–566. https://doi.org/10.1146/annurev-physiol-022516-034339
Ng SC, Lam YT, Tsoi KKF, et al., 2013. Systematic review: the efficacy of herbal therapy in inflammatory bowel disease. Aliment Pharmacol Ther, 38(8):854–863. https://doi.org/10.1111/apt.12464
Opal SM, van der Poll T, 2015. Endothelial barrier dysfunction in septic shock. J Intern Med, 277(3):277–293. https://doi.org/10.1111/joim.12331
Phatak UP, Alper A, Pashankar DS, 2019. Complementary and alternative medicine use in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr, 68(2):157–160. https://doi.org/10.1097/MPG.0000000000002218
Ren JN, Tao QS, Wang XB, et al., 2007. Efficacy of T2 in active Crohn’s disease: a prospective study report. Dig Dis Sci, 52(8):1790–1797. https://doi.org/10.1007/s10620-007-9747-y
Shang AD, Lu YQ, 2015. A case report of severe paraquat poisoning in an HIV-positive patient: an unexpected outcome and inspiration. Medicine (Baltimore), 94(8):e587. https://doi.org/10.1097/MD.0000000000000587
Shi JJ, Gao WQ, Shao F, 2017. Pyroptosis: gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci, 42(4):245–254. https://doi.org/10.1016/j.tibs.2016.10.004
Song SP, Li B, Wu ML, 2014. Empirical study on complex prescription leigongteng decoction attenuation synergistic action in degenerative nephritis rat kidney. Int J Tradit Chin Med, 36(3):223–227 (in Chinese). https://doi.org/10.3760/cma.jissn.1673-4246.2014.03.009
Stefater JA III, Ren SY, Lang RA, et al., 2011. Metchnikoff’s policemen: macrophages in development, homeostasis and regeneration. Trends Mol Med, 17(12):743–752. https://doi.org/10.1016/j.molmed.2011.07.009
Strowig T, Henao-Mejia J, Elinav E, et al., 2012. Inflammasomes in health and disease. Nature, 481(7381):278–286. https://doi.org/10.1038/nature10759
Sun T, Li X, Song H, et al., 2017. MiR-146a aggravates LPS-induced inflammatory injury by targeting CXCR4 in the articular chondrocytes. Cell Physiol Biochem, 44(4): 1282–1294. https://doi.org/10.1159/000485488
Tao QS, Ren JA, Ji ZL, et al., 2009. Maintenance effect of polyglycosides of Tripterygium wilfordii on remission in postoperative Crohn disease. Chin J Gastrointest Surg, 12(5):491–493 (in Chinese). https://doi.org/10.3760/cma.j.issn.1671-0274.2009.05.022
von Moltke J, Ayres JS, Kofoed EM, et al., 2013. Recognition of bacteria by inflammasomes. Annu Rev Immunol, 31: 73–106. https://doi.org/10.1146/annurev-immunol-032712-095944
Wang HR, Pan J, Shang AD, et al., 2017. Time-dependent haemoperfusion after acute paraquat poisoning. Sci Rep, 7(1):2239. https://doi.org/10.1038/s41598-017-02527-0
Wang XY, Zu YY, Huang L, et al., 2017. Treatment of rheumatoid arthritis with combination of methotrexate and Tripterygium wilfordii: a meta-analysis. Life Sci, 171:45–50. https://doi.org/10.1016/j.lfs.2017.01.004
Wang YT, Gao BS, Yao LY, et al., 2015. The effect of tripterygium glycosides on early rejection after kidney transplantation. Chin J Gerontol, 35(21):6190–6191 (in Chinese). https://doi.org/10.3969/j.issn.1005-9202.2015.21.090
Wu F, Han M, Wilson JX, 2009. Tripterine prevents endothelial barrier dysfunction by inhibiting endogenous peroxynitrite formation. Br J Pharmacol, 157(6):1014–1023. https://doi.org/10.1111/j.1476-5381.2009.00292.x
Wu R, Li Y, Guo Z, et al., 2013. Triptolide ameliorates ileocolonic anastomosis inflammation in IL-10 deficient mice by mechanism involving suppression of miR-155/SHIP-1 signaling pathway. Mol Immunol, 56(4):340–346. https://doi.org/10.1016/j.molimm.2013.05.006
Xin WY, Wang QY, Zhang D, et al., 2017. A new mechanism of inhibition of IL-1β secretion by celastrol through the NLRP3 inflammasome pathway. Eur J Pharmacol, 814: 240–247. https://doi.org/10.1016/j.ejphar.2017.08.036
Xiong Y, Yan YL, Li YZ, 2018. Tripterine alleviates LPS-induced inflammatory injury by up-regulation of miR-146a in HaCaT cells. Biomed Pharmacother, 105:798–804. https://doi.org/10.1016/j.biopha.2018.05.008
Xu B, Jiang MZ, Chu Y, et al., 2018. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice. J Hepatol, 68(4):773–782. https://doi.org/10.1016/j.jhep.2017.11.040
Xu YG, Lu YQ, 2019. Systematic review and meta-analysis of the efficacy and safety of immunosuppressive pulse therapy in the treatment of paraquat poisoning. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 20(7):588–597. https://doi.org/10.1631/jzus.B1800640
Yan YH, Shang PZ, Lu QJ, et al., 2012. Triptolide regulates T cell-mediated immunity via induction of CD11Clow dendritic cell differentiation. Food Chem Toxicol, 50(7): 2560–2564. https://doi.org/10.1016/j.fct.2012.04.033
Yang YQ, Wu YF, Xu FF, et al., 2019. Tripterygium glycoside fraction n2: alleviation of DSS-induced colitis by modulating immune homeostasis in mice. Phytomedicine, 58: 152855. https://doi.org/10.1016/j.phymed.2019.152855
Yao JC, Jiang ZZ, Duan WG, et al., 2008. Involvement of mitochondrial pathway in triptolide-induced cytotoxicity in human normal liver L-02 cells. Biol Pharm Bull, 31(4):592–597. https://doi.org/10.1248/bpb.31.592
Yu XJ, Zhao Q, Zhang XX, et al., 2017. Celastrol ameliorates inflammation through inhibition of NLRP3 inflammasome activation. Oncotarget, 8(40):67300–67314. https://doi.org/10.18632/oncotarget.18619
Zhang WD, 2007. Effect of triptolide combined with glycyrrhizin on collagen-induced arthritis in rats. PhD Thesis, China Academy of Chinese Medical Sciences, Beijing, China (in Chinese).
Zhao DQ, Li SW, Liao T, et al., 2018. Triptolide inhibits donor-specific antibody production and attenuates mixed antibody-mediated renal allograft injury. Am J Transplant, 18(5):1083–1095. https://doi.org/10.1111/ajt.14602
Zhao JX, Di TT, Wang Y, et al., 2016. Multi-glycoside of Tripterygium wilfordii Hook. f. ameliorates imiquimod-induced skin lesions through a STAT3-dependent mechanism involving the inhibition of Th17-mediated inflammatory responses. Int J Mol Med, 38(3):747–757. https://doi.org/10.3892/ijmm.2016.2670
Zhou H, Guo W, Long C, et al., 2015. Triptolide inhibits proliferation of Epstein—Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1. Biochem Biophys Res Commun, 456(3):815–820. https://doi.org/10.1016/j.bbrc.2014.12.023
Zhou XX, Liang MX, 2009. Study on the effect of Tripterygium wilfordii compatibility prescription on reproductive system of nephrotic female rats. Pharmacol Clin Chin Mat Med, 25(4):56–58 (in Chinese).
Acknowledgments
We thank Jiao-jiao YANG (the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China) for providing assistance with language editing.
Author information
Authors and Affiliations
Contributions
Cong-ying SONG and Yuan-qiang LU participated in the design. Cong-ying SONG and Ying-ge XU wrote this article. Yuan-qiang LU checked the final version. All authors have read and approved the final manuscript.
Corresponding author
Ethics declarations
Cong-ying SONG, Ying-ge XU, and Yuan-qiang LU declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Project supported by the Foundation of Key Discipline Construction of Zhejiang Province for Traditional Chinese Medicine (No. 2017XK-A36), the Medical and Health Science Foundation of Zhejiang Province (No. 2019327552), the Foundation of Key Research Project of Zhejiang Province for Traditional Chinese Medicine (No. 2019ZZ014), and the Foundation of Science and Technology Department of Zhejiang Province for Beneficial Technology Research of Social Development (No. 2015C33146), China
Rights and permissions
About this article
Cite this article
Song, Cy., Xu, Yg. & Lu, Yq. Use of Tripterygium wilfordii Hook F for immune-mediated inflammatory diseases: progress and future prospects. J. Zhejiang Univ. Sci. B 21, 280–290 (2020). https://doi.org/10.1631/jzus.B1900607
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B1900607