Immunosuppressive, anti-inflammatory and anti-cancer properties of triptolide: A mini review

Document Type: Mini Review Article


1 Montclair State University Department of Biology 1 Normal Ave Montclair NJ 07043, +1 973-655-7982

2 Montclair State University Department of Biology 1 Normal Avenue Montclair NJ 07043, USA +1 973-655-7982


Objective: Triptolide, the active component of Tripterygium wilfordii Hook F has been used to treat autoimmune and inflammatory conditions for over two hundred years in traditional Chinese medicine. However, the processes through which triptolide exerts immunosuppression and anti-inflammation are not understood well. In this review, we discuss the autoimmune disorders and inflammatory conditions that are currently treated with triptolide. Triptolide also possesses anti-tumorigenic effects. We discuss the toxicity of various triptolide derivatives and offer suggestions to improve its safety. This study also examines the clinical trials that have investigated the efficacy of triptolide. Our aim is to examine the mechanisms that are responsible for the immunosuppressive, anti-inflammatory, and anti-cancer effects of triptolide.
Materials and Methods: The present review provides a comprehensive summary of the literature with respect to the immunosuppressive, anti-inflammatory, and anti-cancer properties of triptolide.
Results: Triptolide possesses immunosuppressive, anti-inflammatory, and anti-cancer effects.
Conclusion: Triptolide can be used alone or in combination with existing therapeutic modalities as novel treatments for autoimmune disorders, cancers, and for immunosuppression.


Main Subjects

Antonoff MB, Chugh R, Borja-Cacho D, Dudeja V, Clawson KA, Skube SJ, Sorenson BS, Saltzman DA, Vickers SM, Saluja AK. 2009. Triptolide therapy for neuroblastoma decreases cell viability in vitro and inhibits tumor growth in vivo. Surgery, 146: 282-290.

Brosnan CF, Cannella B, Battistini L, Raine CS. 1995. Cytokine localization in multiple sclerosis lesions: correlation with adhesion molecule expression and reactive nitrogen species. Neurology, 45: S16-21.

Carter BZ, Mak DH, Shi Y, Fidler JM, Chen R, Ling X, Plunkett W, Andreeff M. 2012. MRx102, a triptolide derivative, has potent antileukemic activity in vitro and in a murine model of AML. Leukemia, 26:443-450.

Chang D M, Chang W Y, Kuo S Y, Chang M L. 1997. The effects of traditional antirheumatic herbal medicines on immune response cells. J Rheumatol, 24: 436-441.

Chen, BJ 2001. Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F. Leuk Lymphoma, 42: 253-265.

Chen BJ, Chen Y, Cui X, Fidler JM, Chao NJ. 2000. Prevention of graft-versus-host disease by a novel immunosuppressant, PG490-88, through inhibition of alloreactive T cell expansion. Transplantation, 70: 1442-1447.

Chen BJ, Chen Y, Cui X, Fidler JM, Chao NJ. 2002. Mechanisms of tolerance induced by PG490-88 in a bone marrow transplantation model. Transplantation, 73: 115-121.

Chen X, Murakami T, Oppenheim JJ, Howard OM. 2005. Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking. Blood, 106: 2409-2416.

Chen YZ, Gao Q, Zhao XZ, Chen XM, Zhang F, Chen J, Xu CG, Sun LL, Mei CL. 2010. Meta-analysis of Tripterygium wilfordii Hook F in the immunosuppressive treatment of IgA nephropathy. Intern Med, 49:2049-2055.

Chen Z, Sangwan V, Banerjee S, Chugh R, Dudeja V, Vickers SM, Saluja AK. 2014. Triptolide sensitizes pancreatic cancer cells to TRAIL-induced activation of the death receptor pathway. Cancer Lett, 348: 156-166.

Du X, Zhang H, Fu X. 1998. [Clinical study on tripterygium wilfordii complex ester tablet in treating rheumatoid arthritis]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 18: 88-91.

Fidler JM, Li K, Chung C, Wei K, Ross JA, Gao M, Rosen GD. 2003. PG490-88, a derivative of triptolide, causes tumor regression and sensitizes tumors to chemotherapy. Mol Cancer Ther, 2: 855-862.

Fidler JM, An J, Carter BZ, Andreeff M. 2014. Preclinical antileukemic activity, toxicology, toxicokinetics and formulation development of triptolide derivative MRx102. Cancer Chemother Pharmacol, 73:961-974.

First MR, Fitzsimmons WE. 2004. New drugs to improve transplant outcomes. Transplantation, 77: S88-92.

Fu Q, Huang X, Shu B, Xue M, Zhang P, Wang T, Liu L, Jiang Z, Zhang L. 2011. Inhibition of mitochondrial respiratory chain is involved in triptolide-induced liver injury. Fitoterapia, 82: 1241-1248.

Fu YF, Zhu YN, Ni J, Zhong XG, Tang W, Zhou R, Zhou Y, Dong JR, He PL, Wan H, Li YC, Yang YF, Zuo JP. 2006. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, prevents experimental autoimmune encephalomyelitis via inhibiting T cell activation. J Neuroimmunol, 175: 142-151.

Gao Y, Chen D. 2000. [Clinical study on effect of Tripterygium wilfordii Hook. f. on uterin leiomyoma]. Zhonghua Fu Chan Ke Za Zhi, 35: 430-432.

Gelderblom H, Verweij J, Nooter K, Sparreboom A. 2001. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer, 37: 1590-1598.

Geng Y, Fang M, Wang J, Yu H, Hu Z, Yew DT, Chen W. 2012. Triptolide down-regulates COX-2 expression and PGE2 release by suppressing the activity of NF-κB and MAP kinases in lipopolysaccharide-treated PC12 cells. Phytother Res, 26: 337-343.

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. 2009. Comparison of Tripterygium wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis: a randomized trial. Ann Intern Med, 151: 229-240, W249-251.

Graziose R, Lila MA, Raskin I. 2010. Merging traditional Chinese medicine with modern drug discovery technologies to find novel drugs and functional foods. Curr Drug Discov Technol, 7: 2-12.

Han R, Rostami-Yazdi M, Gerdes S, Mrowietz U. 2012. Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases. Br J Clin Pharmacol, 74:424-436.

He MF, Huang YH, Wu LW, Ge W, Shaw PC, But PP. 2010. Triptolide functions as a potent angiogenesis inhibitor. Int J Cancer, 126: 266-278.

Hong Y, Zhou W, Li K, Sacks SH. 2002. Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells. Kidney Int, 62: 1291-1300.

Hongqin T, Xinyu L, Heng G, Lanfang X, Yongfang W, Shasha S. 2011. Triptolide inhibits IFN-γ signaling via the Jak/STAT pathway in HaCaT keratinocytes. Phytother Res, 25: 1678-1685.

Hoyle GW, Hoyle CI, Chen J, Chang W, Williams RW, Rando RJ. 2010. Identification of triptolide, a natural diterpenoid compound, as an inhibitor of lung inflammation. Am J Physiol Lung Cell Mol Physiol, 298: L830-836.

Hu YP, Tan ZJ, Wu XS, Liu TY, Jiang L, Bao RF, Shu YJ, Li ML, Weng H, Ding Q, Tao F, Liu YB. 2014. Triptolide induces s phase arrest and apoptosis in gallbladder cancer cells. Molecules, 19: 2612-2628.

Huang SH, Lin GJ, Chu CH, Yu JC, Chen TW, Chen YW, Chien MW, Chu CC, Sytwu HK. 2013. Triptolide ameliorates autoimmune diabetes and prolongs islet graft survival in nonobese diabetic mice. Pancreas, 42: 442-451.

Jänicke RU, Sprengart ML, Wati MR, Porter AG. 1998. Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem, 273:9357–9360.

Jefferson JA, Shankland SJ, Pichler RH. 2008. Proteinuria in diabetic kidney disease: a mechanistic viewpoint. Kidney Int, 74: 22-36.

Ji W, Li J, Lin Y, Song YN, Zhang M, Ke Y, Ren Y, Deng X, Zhang J, Huang F, Yu D. 2010. Report of 12 cases of ankylosing spondylitis patients treated with Tripterygium wilfordii. Clin Rheumatol, 29: 1067-1072.

Jiang, X. 1994. Clinical observations on the use of the Chinese herb Tripterygium wilfordii Hook for the treatment of nephrotic syndrome. Pediatr Nephrol, 8: 343-344.

Kim YH, Lee SH, Lee JY, Choi SW, Park JW, Kwon TK. 2004. Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-kappa B and c-Jun NH2-terminal kinase. Eur J Pharmacol, 494: 1-9.

Kizelsztein P, Komarnytsky S, Raskin I. 2009. Oral administration of triptolide ameliorates the clinical signs of experimental autoimmune encephalomyelitis (EAE) by induction of HSP70 and stabilization of NF-kappaB/IkappaBalpha transcriptional complex. J Neuroimmunol, 217:28-37.

Klawitter M, Quero L, Klasen J, Liebscher T, Nerlich A, Boos N, Wuertz K. 2012. Triptolide exhibits anti-inflammatory, anti-catabolic as well as anabolic effects and suppresses TLR expression and MAPK activity in IL-1β treated human intervertebral disc cells. Eur Spine J, 21 Suppl 6: S850-859.

Krakauer T, Chen X, Howard OM, Young HA. 2005. Triptolide attenuates endotoxin- and staphylococcal exotoxin-induced T-cell proliferation and production of cytokines and chemokines. Immunopharmacol Immunotoxicol, 27: 53-66.

Krishna G, Liu K, Shigemitsu H, Gao M, Raffin TA, Rosen GD. 2001. PG490-88, a derivative of triptolide, blocks bleomycin-induced lung fibrosis. Am J Pathol, 158: 997-1004.

Krosch TC, Sangwan V, Banerjee S, Mujumdar N, Dudeja V, Saluja AK, Vickers SM. 2013. Triptolide-mediated cell death in neuroblastoma occurs by both apoptosis and autophagy pathways and results in inhibition of nuclear factor-kappa B activity. Am J Surg, 205: 387-396.

Leonard CT, Soccal PM, Berry GJ, Doyle RL, Theodore J, Duncan SR, Rosen GD. 2002. PG490-88, a derivative of triptolide, attenuates obliterative airway disease in a mouse heterotopic tracheal allograft model. J Heart Lung Transplant, 21: 1314-1318.

Li J, Jin J, Li M, Guan C, Wang W, Zhu S, Qiu Y, Huang M, Huang Z. 2012. Role of Nrf2 in protection against triptolide-induced toxicity in rat kidney cells. Toxicol Lett, 213: 194-202.

Li, LF. 2000. Treatment of pyoderma gangrenosum with oral Tripterygium wilfordii multiglycoside. J Dermatol 27: 478-481.

Li XJ, Jiang ZZ, Zhang LY. 2014. Triptolide: progress on research in pharmacodynamics and toxicology. J Ethnopharmacol, 155: 67-79.

Li Y, Yu C, Zhu WM, Xie Y, Qi X, Li N, Li JS. 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: 2467-2474.

Li Y, Tian Y, Zhu W, Gong J, Zhang W, Yu C, Gu L, Li N, Li J. 2013. Triptolide induces suppressor of cytokine signaling-3 expression and promotes lamina propria mononuclear cells apoptosis in Crohn's colitis. Int Immunopharmacol, 16: 268-274.

Li G, Ren J, Wang G, Gu G, Hu D, Ren H, Hong Z, Wu X, Liu S, Li J. 2014. T2 enhances in situ level of Foxp3+ regulatory cells and modulates inflammatory cytokines in Crohn's disease. Int Immunopharmacol, 18:244-248.

Liacini A, Sylvester J, Zafarullah M. 2005. Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes. Biochem Biophys Res Commun, 327: 320-327.

Lin LM, Qi XM. 2005. Comparative observation on the effects of Radix tripterygium hypoglaucum tablet and Tripterygium glycosides tablet in treating erosive oral lichen planus. Chin J Integr Med, 11: 149-150.

Lin N, Sato T, Ito A. 2001. Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts. Arthritis Rheum, 44: 2193-2200.

Lin N, Liu C, Xiao C, Jia H, Imada K, Wu H, Ito A. 2007. Triptolide, a diterpenoid triepoxide, suppresses inflammation and cartilage destruction in collagen-induced arthritis mice. Biochem Pharmacol, 73: 136-146.

Lipsky PE, Tao XL. 1997. A potential new treatment for rheumatoid arthritis: thunder god vine. Semin Arthritis Rheum, 26: 713-723.

Liu HK, Perrier S, Lipina C, Finlay D, McLauchlan H, Hastie CJ, Hundal HS, Sutherland C. 2006. Functional characterisation of the regulation of CAAT enhancer binding protein alpha by GSK-3 phosphorylation of Threonines 222/226. BMC Mol Biol, 7: 14.

Liu J, Wu QL, Feng YH, Wang YF, Li XY, Zuo JP. 2005. Triptolide suppresses CD80 and CD86 expressions and IL-12 production in THP-1 cells. Acta Pharmacol Sin, 26: 223-227.

Liu J, Chen X, Zhang Y, Miao H, Liu K, Li L, Zhong D. 2011. Derivatization of (5R)-hydroxytriptolide from benzylamine to enhance mass spectrometric detection: application to a Phase I pharmacokinetic study in humans. Anal Chim Acta, 689: 69-76.

Liu L, Salnikov AV, Bauer N, Aleksandrowicz E, Labsch S, Nwaeburu C, MatternJ, Gladkich J, Schemmer P, Werner J, Herr I. 2014. Triptolide reverses hypoxia-induced epithelial-mesenchymal transition and stem-like features in pancreatic cancer by NF-κB downregulation. Int J Cancer, 134: 2489-2503.

Liu Q, Chen T, Chen H, Zhang M, Li N, Lu Z, Ma P, Cao X. 2004. Triptolide (PG-490) induces apoptosis of dendritic cells through sequential p38 MAP kinase phosphorylation and caspase 3 activation. Biochem Biophys Res Commun, 319: 980-986.

Liu Q, Chen T, Chen G, Shu X, Sun A, Ma P, Lu L, Cao X. 2007. Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2 expression through PI3-K/Akt and NF-kappaB pathways. Mol Immunol, 44: 2686-2696.

Liu Y, Chen Y, Liu FQ, Lamb JR, Tam PK. 2008. Combined treatment with triptolide and rapamycin prolongs graft survival in a mouse model of cardiac transplantation. Transpl Int, 21: 483-494.

Lu Y, Fukuda K, Nakamura Y, Kimura K, Kumagai N, Nishida T. 2005. Inhibitory effect of triptolide on chemokine expression induced by proinflammatory cytokines in human corneal fibroblasts. Invest Ophthalmol Vis Sci, 46: 2346-2352.

Lu Y, Liu Y, Fukuda K, Nakamura Y, Kumagai N, Nishida T. 2006. Inhibition by triptolide of chemokine, proinflammatory cytokine, and adhesion molecule expression induced by lipopolysaccharide in corneal fibroblasts. Invest Ophthalmol Vis Sci, 47: 3796-3800.

Lu Y, Zhang Y, Li L, Feng X, Ding S, Zheng W, Li J, Shen P. 2014. TAB1: a target of triptolide in macrophages. Chem Biol 21: 246-256.

Ma TY, Iwamoto GK, Hoa NT, Akotia V, Pedram A, Boivin MA, Said HM. 2004. TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol, 286: G367-376.

Martin R, McFarland HF, McFarlin DE. 1992. Immunological aspects of demyelinating diseases. Annu Rev Immunol, 10: 153-187.

Matta R, Wang X, Ge H, Ray W, Nelin LD, Liu Y. 2009. Triptolide induces anti-inflammatory cellular responses. Am J Transl Res, 1: 267-282.

Meng C, Zhu H, Song H, Wang Z, Huang G, Li D, Ma Z, Ma J, Qin Q, Sun X, Ma J. 2014. Targets and molecular mechanisms of triptolide in cancer therapy. Chin J Cancer Res, 26: 622-626.

Owa C, Messina ME Jr, Halaby R.2013. Triptolide induces lysosomal-mediated programmed cell death in MCF-7 breast cancer cells. Int J Womens Health, 5: 557-569.

Pan F, Fisniku O, Wynn C, Erickson LM, Crews G, Jang MS, Sudo Y, Tamura K, Kobayashi M, Benediktsson H, Jiang H. 2005. PG490-88, a new immunosuppressant, effectively prevents acute and chronic rejection in rat renal allografts. Transplant Proc, 37: 134-136.

Peng A, Gu Y, Lin SY. 2005. Herbal treatment for renal diseases. Ann Acad Med Singapore, 34: 44-51.

Peng AP, Wang XY, Zhuang JH. 2014. [Triptolide inhibites Th17 cell differentiation via regulating cyclooxygenase-2/ prostaglandin E2 axis in synovial fibroblasts from rheumatoid arthritis]. Zhongguo Zhong Yao Za Zhi, 39: 536-539.

Phillips PA, Dudeja V, McCarroll JA, Borja-Cacho D, Dawra RK, Grizzle WE, Vickers SM, Saluja AK. 2007. Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein 70. Cancer Res, 67: 9407-9416.

Premkumar V, Dey M, Dorn R, Raskin I. 2010. MyD88-dependent and independent pathways of Toll-Like Receptors are engaged in biological activity of Triptolide in ligand-stimulated macrophages. BMC Chem Biol, 10: 3.

Qiu D, Kao PN. 2003. Immunosuppressive and anti-inflammatory mechanisms of triptolide, the principal active diterpenoid from the Chinese medicinal herb Tripterygium wilfordii Hook. f. Drugs R D, 4: 1-18.

Ren J, Tao Q, Wang X, Wang Z, Li J. 2007. Efficacy of T2 in active Crohn's disease: a prospective study report. Dig Dis Sci, 52: 1790-1797.

Shao H, Ma J, Guo T, Hu R. 2014. Triptolide induces apoptosis of breast cancer cells via a mechanism associated with the Wnt/β-catenin signaling pathway. Exp Ther Med, 8: 505-508.

Song HX, Gong J, Chen W. 2005. [Effect of triptolide on urinary monocyte chemottractant protein-1 in patients with diabetic nephropathy]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 25: 416-418.

Sun L, Li H, Huang X, Wang T, Zhang S, Yang J, Huang S, Mei H, Jiang Z, Zhang L. 2013. Triptolide alters barrier function in renal proximal tubular cells in rats. Toxicol Lett, 223: 96-102.

Sutton C, Brereton C, Keogh B, Mills KH, Lavelle EC. 2006. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med, 203: 1685-1691.

Tao X, Lipsky PE. 2000. The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Rheum Dis Clin North Am, 26: 29-50, viii.

Tao X, Cai JJ, Lipsky PE. 1995. The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract (T2) of Tripterygium wilfordii Hook. F. J Pharmacol Exp Ther, 272: 1305-1312.

Tao X, Davis LS, Hashimoto K, Lipsky PE. 1996. The Chinese herbal remedy, T2, inhibits mitogen-induced cytokine gene transcription by T cells, but not initial signal transduction. J Pharmacol Exp Ther, 276: 316-325.

Tao X, Cush JJ, Garret M, Lipsky PE. 2001. A phase I study of ethyl acetate extract of the Chinese antirheumatic herb Tripterygium wilfordii hook F in rheumatoid arthritis. J Rheumatol, 28: 2160-2167.

Tao X, Younger J, Fan FZ, Wang B, Lipsky PE. 2002. Benefit of an extract of Tripterygium Wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study. Arthritis Rheum, 46: 1735-1743.

Tao X, Fan F, Hoffmann V, Gao CY, Longo NS, Zerfas P, Lipsky PE. 2008. Effective therapy for nephritis in (NZB x NZW)F1 mice with triptolide and tripdiolide, the principal active components of the Chinese herbal remedy Tripterygium wilfordii Hook F. Arthritis Rheum, 58: 1774-1783.

Tong X, Zheng S, Jin J, Zhu L, Lou Y, Yao H. 2007. Triptolide inhibits cyclooxygenase-2 and inducible nitric oxide synthase expression in human colon cancer and leukemia cells. Acta Biochim Biophys Sin (Shanghai), 39: 89-95

van Eden W. 2009. Protective and therapeutic effect of triptolide in EAE explained by induction of major stress protein HSP70. J Neuroimmunol, 217:10-11.

Vanderlugt CL, Miller SD. 2002. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol, 2: 85-95.

Wang XH, Zhang ZY. 2001. [Effect of tripterygium polyglucoside on T-lymphocyte subsets and serum interleukin-5 level in asthma patients]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 21:25-27.

Wang B, Ma L, Tao X, Lipsky PE. 2004a. Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription. Arthritis Rheum, 50: 2995-2303.

Wang J, Wang YT, Shao JQ, Wang X, Du H. 2004b. [Immunosuppressive therapies in patients with Graves' ophthalmopathy]. Zhonghua Nei Ke Za Zhi, 43: 125-127.

Wang X, Sun H, Chen G, Liu W, Wise Y, Yung C, Sudo Y, Tamura K, Garcia B, Zhong R. 2005. Immunosuppression with a combination of pg490-88 and a subtherapeutic dose of FK506 in a canine renal allograft model. Transplantation, 79: 1537-1544.

Wang Y, Mei Y, Feng D, Xu L. 2008. Triptolide modulates T-cell inflammatory

responses and ameliorates experimental autoimmune encephalomyelitis. J Neurosci Res, 86:2441-2449.

Wang X, Zhang L, Duan W, Liu B, Gong P, Ding Y, Wu X. 2014. Anti-inflammatory effects of triptolide by inhibiting the NF-κB signalling pathway in LPS-induced acute lung injury in a murine model. Mol Med Rep, 10: 447-452.

Wei X, Gong J, Zhu J, Wang P, Li N, Zhu W, Li J. 2008. The suppressive effect of triptolide on chronic colitis and TNF-alpha/TNFR2 signal pathway in interleukin-10 deficient mice. Clin Immunol, 129: 211-218.

Wei D, Huang Z. 2014. Anti-inflammatory effects of triptolide in LPS-induced acute lung injury in mice. Inflammation, 37: 1307-1316.

Westerheide SD, Kawahara TL, Orton K, Morimoto RI. 2006. Triptolide, an inhibitor of the human heat shock response that enhances stress-induced cell death. J Biol Chem, 281: 9616-9622.

Whitham RH, Bourdette DN, Hashim GA, Herndon RM, Ilg RC, Vandenbark AA, OffnerH. 1991. Lymphocytes from SJL/J mice immunized with spinal cord respond selectively to a peptide of proteolipid protein and transfer relapsing demyelinating experimental autoimmune encephalomyelitis. J Immunol, 146: 101-107.

Wong KF, Yuan Y, Luk JM. 2012. Tripterygium wilfordii bioactive compounds as anticancer and anti-inflammatory agents. Clin Exp Pharmacol Physiol, 39: 311-320.

Wong KF, Chan JK, Chan KL, Tam P, Yang D, Fan ST, Luk JM. 2008. Immunochemical characterization of the functional constituents of Tripterygium wilfordii contributing to its anti-inflammatory property. Clin Exp Pharmacol Physiol, 35: 55-59.

Wu YJ, Lao ZY, Zhang ZL. 2001. [Clinical observation on small doses Tripterygium wilfordii polyglycoside combined with methotrexate in treating rheumatoid arthritis]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 21: 895-896.

Wu SX, Guo NR. 2005. Clinical observation on effect of triptolide tablet in treating patients with psoriasis vulgaris. Chin J Integr Med, 11: 147-148.

Wu R, Li Y, Guo Z, Gong J, Zhu W, Li N, Li J. 2013a. Triptolide ameliorates ileocolonic anastomosis inflammation in IL-10 deficient mice by mechanism involving suppression of miR-155/SHIP-1 signaling pathway. Mol Immunol, 56: 340-346.

Wu L, Mao J, Jin X, Fu H, Shen H, Wang J, Liu A, Shu Q, Du L. 2013b. Efficacy of triptolide for children with moderately severe Henoch-Schönlein purpura nephritis presenting with nephrotic range proteinuria: a prospective and controlled study in China. Biomed Res Int, 2013:292865.

Xin MJ, Cui SH, Liu S, Sun HC, Li F, Sun JB, Luo B. 2010. Triptolide prolonged allogeneic islet graft survival in chemically induced and spontaneously diabetic mice without impairment of islet function. Hepatobiliary Pancreat Dis Int, 9: 312-318.

Xu WY, Zheng JR, Lu XY. 1985. Tripterygium in dermatologic therapy. Int J Dermatol, 24: 152-157.

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

Yang S, Chen J, Guo Z, Xu XM, Wang L, Pei XF, Yang J, Underhill CB, Zhang L. 2003. Triptolide inhibits the growth and metastasis of solid tumors. Mol Cancer Ther, 2: 65-72.

Yu C, Shan T, Feng A, Li Y, Zhu W, Xie Y, Li N, Li J. 2011. Triptolide ameliorates Crohn's colitis is associated with inhibition of TLRs/NF-κB signaling pathway. Fitoterapia, 82: 709-715.

Zeng R, Zeng L, Chen Y, Zhao F, Li R, Wen L, Zhang C. 2011. Triptolide-induced apoptosis by inactivating nuclear factor-kappa B apoptotic pathway in multiple myeloma in vitro. J Huazhong Univ Sci Technolog Med Sci, 31: 446-451.

Zhang J, Liu L, Mu X, Jiang Z, Zhang L. 2012. Effect of triptolide on estradiol release from cultured rat granulosa cells. Endocr J, 59: 473-481.

Zhang X, Xia J, Ye H. 2000. [Effect of Tripterygium polyglycoside on interleukin-6 in patients with Guillain-Barre syndrome]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 20: 332-334.

Zhang XZ, Li S, Wu XZ. 1994. [Effects of Tripterygiitotorum in the treatment of insulin dependent diabetes mellitus with islet transplantation]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 14: 451-453.

Zhang Y, Ma X. 2010. Triptolide inhibits IL-12/IL-23 expression in APCs via CCAAT/enhancer-binding protein alpha. J Immunol, 184: 3866-3877.

Zheng CX, Chen ZH, Zeng CH, Qin WS, Li LS, Liu ZH. 2008. Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro. Kidney Int 74: 596-612.

Zhou J, Zhu Q, Yang X. 1999. [Clinical observation of side effects of Tripterygium preparation]. Zhongguo Zhong Xi Yi Jie He Za Zhi, 19: 77-79.

Zhou R, Zhang F, He PL, Zhou WL, Wu QL, Xu JY, Zhou Y, Tang W, Li XY, Yang YF, Li YC, Zuo JP. 2005. (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide analog mediates immunosuppressive effects in vitro and in vivo. Int Immunopharmacol, 5: 1895-1903.

Zhou R, Tang W, Ren YX, He PL, Yang YF, Li YC, Zuo JP. 2006a. Preventive effects of (5R)-5-hydroxytriptolide on concanavalin A-induced hepatitis. Eur J Pharmacol, 537: 181-189.

Zhou R, Wang JX, Tang W, He PL, Yang YF, Li YC, Li XY, Zuo JP. 2006b. (5R)-5-hydroxytriptolide inhibits IFN-gamma-related signaling. Acta Pharmacol Sin, 27: 1616-1621.

Zhou R, Tang W, Ren YX, He PL, Zhang F, Shi LP, Fu YF, Li YC, Ono S, Fujiwara H, Yang YF, Zuo JP. 2006c. (5R)-5-hydroxytriptolide attenuated collagen-induced arthritis in DBA/1 mice via suppressing interferon-gamma production and its related signaling. J Pharmacol Exp Ther, 318: 35-44.

Zhou R, Tang W, He PL, Yang YF, Li YC, Zuo JP. 2009. (5R)-5-hydroxytriptolide inhibits the immune response of human peripheral blood mononuclear cells. Int Immunopharmacol, 9: 63-69.

Zhu B, Wang YJ, Zhu CF, Lin Y, Zhu XL, Wei S, Lu Y, Cheng XX. 2010. Triptolide inhibits extracellular matrix protein synthesis by suppressing the Smad2 but not the MAPK pathway in TGF-beta1-stimulated NRK-49F cells. Nephrol Dial Transplant, 25: 3180-3191.

Zhu KJ, Shen QY, Cheng H, Mao XH, Lao LM, Hao GL. 2005. Triptolide affects the differentiation, maturation and function of human dendritic cells. Int Immunopharmacol, 5: 1415-1426.

Zhu XZ, Li XY, Liu J. 2004. Recent pharmacological studies on natural products in China. Eur J Pharmacol, 500: 221-230.