Top

Published in:

01-09-2011 | Review

A Chinese herb Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis: mechanism, efficacy, and safety

Authors: Jun Bao, Sheng-Ming Dai

Published in: Rheumatology International | Issue 9/2011

Abstract

Tripterygium wilfordii Hook F (TwHF) is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis (RA). Numerous preclinical studies have demonstrated that the extracts from the root of TwHF inhibit the expression of proinflammatory cytokines, proinflammatory mediators, adhesion molecules, and matrix metalloproteinases by macrophages, lymphocytes, synovial fibroblasts, and chondrocytes. TwHF also induces apoptosis in lymphocytes and synovial fibroblasts and inhibits their proliferation. Except numerous uncontrolled clinical trials, there are some prospective, double-blind, randomized, and placebo/sulfasalazine-controlled trials, also demonstrating greater improvement in RA disease activity by TwHF extract than placebo/sulfasalazine. Radiographic progression in RA may also be retarded by TwHF. Therefore, the immunosuppressive, cartilage protective, and anti-inflammatory effects of TwHF extracts are well demonstrated, and TwHF extract is an alternative disease modifying anti-rheumatic drug (DMARD) for the patients with RA refractory to conventional therapy.

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 272:1305–1312PubMed

Su DF, Song YJ, Li RL (1989) Report of 270 patients with rheumatoid arthritis treated with ethyl acetate extract of Tripterygium wilfordii Hook F. Zhong Yao Yao Li Yu Lin Chuang 5(3):40–42 (in Chinese)

Yu DY (1982) Clinical observation of 144 cases of rheumatoid arthritis treated with glycoside of radix Tripterygium wilfordii. Zhong Yi Za Zhi (7):32–35 (in Chinese)

Lipsky PE, Tao XL (1997) A potential new treatment for rheumatoid arthritis: thunder god vine. Semin Arthr Rheum 26:713–723CrossRef

Canter PH, Lee HS, Ernst E (2006) A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid arthritis. Phytomedicine 13:371–377PubMedCrossRef

Zhang L, Zhang ZX, An DK (1990) The achievements in the studies of chemical components of Tripterygium wilfordii Hook family. Zhongguo Yao Ke Da Xue Xue Bao 21(4):251–256 (in Chinese)

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

Zheng JR, Fang JL, Gu KX, Xu LF, Gao JW, Guo HZ et al. (1987) Screening of active anti-inflammatory-immunosuppressive and antifertile compositions from Tripterygium wilfordii. I. Screening of 8 components from total glucosides of Tripterygium wilfordii (TII). Zhongguo Yi Xue Ke Xue Yuan Xue Bao 9:317–322 (in Chinese)

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

10.

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

11.

Zheng JR, Fang JL, Gu KX, Ti YQ, Xu LF, Gao JW et al. (1987) Screening of active anti-inflammatory-immunosuppressive and antifertile components from Tripterygium wilfordii. II. Screening of 5 monomers from total glucosides of Tripterygium wilfordii (TII). Zhongguo Yi Xue Ke Xue Yuan Xue Bao 9:323–328 (in Chinese)

12.

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

13.

Li LZ, Chert SF, Wang FJ (1986) Effect of triptolide on inflammation and immune function. Zhongguo Yao Li Xue Tong Bao 2:25–28 (in Chinese)

14.

Li LZ, Chen SF, Wang FJ (1982) Pharmacological study of the ethyl acetate extract of Tripterygium wilfordii Hook f. Zhong Cao Yao 13:27–32 (in Chinese)

15.

Tao X, Ma L, Mao Y, Lipsky PE (1999) Suppression of carrageenan-induced inflammation in vivo by an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F. Inflamm Res 48:139–148PubMedCrossRef

16.

Tao X, Schulze-Koops H, Ma L, Cai J, Mao Y, Lipsky PE (1998) Effects of Tripterygium wilfordii Hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E2 production. Arthr Rheum 41:130–138CrossRef

17.

Guo W, Ma L, Tao X (2001) In vitro inhibitive effects of Tripterygium wilfordii on NO production, iNOS activity, and iNOS-mRNA expression in chondrocytes of patients with rheumatoid arthritis. Zhonghua Yi Xue Za Zhi 81:1035–1037 (in Chinese)

18.

Sylvester J, Liacini A, Li WQ, Dehnade F, Zafarullah M (2001) Tripterygium wilfordii Hook f extract suppresses proinflammatory cytokine-induced expression of matrix metalloproteinase genes in articular chondrocytes by inhibiting activating protein-1 and nuclear factor-κB activities. Mol Pharmacol 59:1196–1205PubMed

19.

Li RW, Lin GD, Myers SP, Leach DN (2003) Anti-inflammatory activity of Chinese medicinal vine plants. J Ethnopharmacol 85:61–67PubMedCrossRef

20.

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. Arthr Rheum 44:2193–2200CrossRef

21.

Zhou HF, Niu DB, Xue B, Li FQ, Liu XY, He QH et al (2003) Triptolide inhibits TNF-α, IL-1β and NO production in primary microglial cultures. Neuroreport 14:1091–1109PubMed

22.

Wang B, Ma L, Tao X, Lipsky PE (2004) 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. Arthr Rheum 50:2995–3003CrossRef

23.

Chang DM, Chang WY, Kuo SY, Chang ML (1997) The effects of traditional antirheumatic herbal medicines on immune response cells. J Rheumatol 24:436–441PubMed

24.

Luk JM, Lai W, Tam P, Koo MWL (2000) Suppression of cytokine production and cell adhesion molecule expression in human monocytic cell line THP-1 by Tripterygium wilfordii polysaccharide moiety. Life Sci 67:155–163PubMedCrossRef

25.

Tao XL, Davis LS, Lipsky PE (1991) Effect of an extract of Chinese herbal remedy Tripterygium wilfordii Hook. f. on human immune responses. Arthr Rheum 34:1274–1281CrossRef

26.

Lee GI, Ha JY, Min KR, Nakagawa H, Tsurufuji S, Chang IM, Kim Y (1995) Inhibitory effects of oriental herbal medicines on IL-8 induction in lipopolysaccharide-activated rat macrophages. Planta Med 61:26–30PubMedCrossRef

27.

Wu F, Zhu L, Cui L, Wang X, Zhang S (1993) Effect of Tripterygium wilfordii glycosides (TII) on IL-2 and IL-2R gene transcription. Zhonghua Wei Sheng Wu Xue He Mian Yi Xue Za Zhi 13:193–197 (in Chinese)

28.

Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S et al (1999) Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T- cells and NFkappaB transcriptional activation. J Biol Chem 274:13443–13450PubMedCrossRef

29.

Chan MA, Kohlmeier JE, Branden M, Jung M, Benedict SH (1999) Triptolide is more effective in preventing T cell proliferation and interferon-gamma production than is FK506. Phytother Res 13:464–467PubMedCrossRef

30.

Liu Q, Chen T, Chen G, Li N, Wang J, Ma P, Cao X (2006) Immunosuppressant triptolide inhibits dendritic cell-mediated chemoattraction of neutrophils and T cells through inhibiting Stat3 phosphorylation and NF-κB activation. Biochem Biophys Res Commun 345:1122–1130PubMedCrossRef

31.

Chang DM, Kuo SY, Lai JH, Chang ML (1999) Effects of anti-rheumatic herbal medicines on cellular adhesion molecules. Ann Rheum Dis 58:366–371PubMedCrossRef

32.

Luk JM, Tam P, Fan ST, Koo MWL (2000) Immunosuppressive effects of Tripterygium wilfordii polysaccharide on LPS-stimulated human monocytes. Transpl Proc 32:2013–2015CrossRef

33.

Gu WZ, Brandwein SR, Banerjee S (1992) Inhibition of type II collagen induced arthritis in mice by an immunosuppressive extract of Tripterygium wilfordii Hook f. J Rheumatol 19:682–688PubMed

34.

Gu WZ, Brandwein SR (1998) Inhibition of type II collagen-induced arthritis in rats by triptolide. Int J Immunopharmacol 20:389–400PubMedCrossRef

35.

Tao XL, Shi YP, Cheng XH (1988) Mechanism of treating rheumatoid arthritis with Tripterygium wilfordii Hook. Effects on secretion of total IgM and IgM-rheumatoid factor by peripheral blood mononuclear cells. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 10:361–364 (in Chinese)

36.

Ye WH, Tao XL, Zhang NZ (1990) Mechanism of treating rheumatoid arthritis with polyglycosides of Tripterygium wilfordii Hook. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 12:217–221 (in Chinese)

37.

Li XW, Weir MR (1990) Radix Tripterygium wilfordii—a Chinese herbal medicine with potent immunosuppressive properties. Transplantation 50:82–86PubMedCrossRef

38.

Ho LJ, Chang DM, Chang ML, Kuo SY, Lai JH (1999) Mechanism of immunosuppression of the antirheumatic herb TWHf in human T cells. J Rheumatol 26:14–24PubMed

39.

Yang Y, Liu Z, Tolosa E, Yang J, Li L (1998) Triptolide induces apoptotic death of T lymphocyte. Immunopharmacology 40:139–149PubMedCrossRef

40.

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 319:980–986PubMedCrossRef

41.

Tong KK, Yang D, Yuk-Tat E, Peter C, Chiu KY, Yau KS et al (1999) Downregulation of lymphocyte activity and human synovial fibroblast growth in rheumatoid arthritis by triptolide. Drug Dev Res 47:144–153CrossRef

42.

Maekawa K, Yoshikawa N, Du J, Nishida S, Kitasato H, Okamoto K et al (1999) The molecular mechanism of inhibition of interleukin-1beta-induced cyclooxygenase-2 expression in human synovial cells by Tripterygium wilfordii Hook F extract. Inflamm Res 48:575–581PubMedCrossRef

43.

Liu NT, Yang MH, Luo WF, Wei J, Yuan GH (2006) Inhibitory effects of methotrexate and tripterygium glycosides on chemokine CCL5 production in synoviocytes from patients with rheumatoid arthritis. Di Si Jun Yi Da Xue Xue Bao 27:1113–1115 (in Chinese)

44.

Zhou GW, Shen Q, Jin RJ, Wang XD, Zeng YX, Ye CY (2007) Effects of Tripterygium glycosides (TG) on apoptosis of synovial fibroblasts in rheumatoid arthritis. Zhejiang Lin Chuang Yi Xue 9:1034–1035 (in Chinese)

45.

Kusunoki N, Yamazaki R, Kitasato H, Beppu M, Aoki H, Kawai S (2004) Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts. BMC Pharmacol 4:2PubMedCrossRef

46.

Liu H, Liu ZH, Chen ZH, Yang JW, Li LS (2000) Triptolide: a potent inhibitor of NF-kappa B in T-lymphocytes. Acta Pharmacol Sin 21:782–786PubMed

47.

Zhang Q, Shi Y, Tan W, Wang F (2008) Effect of triptolide on the changes of VEGF and MMP-9 levels in the rheumatoid arthritis fibroblast-like synoviocyte line, MH7A. Nanjing Yi Ke Da Xue Xue Bao 28:902–905 (in Chinese)

48.

Mao X, Sun S, Pei Z, Zhang L (2009) Inhibitory effect of triptolide on interleukin-18 and its receptor in rheumatoid arthritis synovial fibroblasts. Xi Bao Yu Feng Zi Mian Yi Xue Za Zhi 25:606–611 (in Chinese)

49.

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 327:320–327PubMedCrossRef

50.

Yu KT, Nuss G, Boyce R, Jariwala N, Owens G, Pennetti A et al (1994) Inhibition of IL-1 release from human monocytes and suppression of streptococcal cell wall and adjuvant-induced arthritis in rats by an extract of Tripterygium wilfordii Hook. Gen Pharmacol 25:1115–1122PubMed

51.

Asano K, Matsuishi J, Yu Y, Kasahara T (1998) Hisamitsu T. Suppressive effects of Tripterygium wilfordii Hook f., a traditional Chinese medicine, on collagen arthritis in mice. Immunopharmacology 39:117–126PubMedCrossRef

52.

Luo B, Hu Y, Zhang M, Tu S, Zeng K (2006) Effect of glycoside of Tripterygium wilfordii Hook. F on expression of receptor activator of nuclear factor-κB ligand and osteoprotegerin in joints of rat with adjuvant-induced arthritis. Yi Yao Dao Bao 25:395–397 (in Chinese)

53.

Zhang BH, Wang LY, Zheng EZ (1985) Study on the pharmacological action of total alkaloids in Tripterygium hypoglaucum Hutch. Zhong Cao Yao 16:360–363 (in Chinese)

54.

Xiao C, Zhou J, He Y, Jia H, Zhao L, Zhao N, Lu A (2009) Effects of triptolide from Radix Tripterygium wilfordii (Leigongteng) on cartilage cytokines and transcription factor NF-κB: a study on induced arthritis in rats. Chin Med 4:13PubMedCrossRef

55.

Tu S, Hu Y, Weng G, Lu F, Zhang M, Lai X, Liu P (2006) Triptolide induces apoptosis of rat synoviocytes in collagen-induced arthritis. Zhongguo Bin Li Sheng Li Za Zhi 22:630–633

56.

Wang Y, Wei D, Lai Z, Le Y (2006) Triptolide inhibits CC chemokines expressed in rat adjuvant-induced arthritis. Int Immunopharmacol 6:1825–1832PubMedCrossRef

57.

Wang Y, Jia L, Wu CY (2008) Triptolide inhibits the differentiation of Th17 cells and suppresses collagen-induced arthritis. Scand J Immunol 68:383–390PubMedCrossRef

58.

Zhou J, Xiao C, Zhao LH, Jia HW, Zhao N, Lu C et al (2006) The effect of triptolide on CD4 + and CD8 + cells in Peyer’s patch of SD rats with collagen induced arthritis. Int Immunopharmacol 6:198–203PubMedCrossRef

59.

Xiao C, Lu C, Zhao L, Liu Z, Zhang W, He Y et al (2006) The effects of triptolide on enteric mucosal immune responses of DBA/1 mice with collagen-induced arthritis. Planta Med 72:1268–1272PubMedCrossRef

60.

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 28:2160–2167PubMed

61.

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. Arthr Rheum 46:1735–1743CrossRef

62.

Goldbach-Mansky R, Wilson M, Fleischmann R, Olsen N, Silverfield J, Kempf P et al. (2009) Comparison of Tripterygium wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis: a randomized trial. Ann Intern Med 151:229–240, W49–W51

63.

Tao XL, Sun Y, Dong Y, Xiao YL, Hu DW, Shi YP et al (1989) A prospective, controlled, double-blind, cross-over study of Tripterygium wilfordii Hook F in treatment of rheumatoid arthritis. Chin Med J (Engl) 102:327–332

64.

Cibere J, Deng Z, Lin Y, He Y, Wang Z, Thorne A et al (2003) A randomized double blind placebo controlled trial of topical Tripterygium wilfordii in rheumatoid arthritis: Reanalyais using logistic regression. J Rheumatol 30:465–467PubMed

65.

Wen C (1993) The effects of Tripterygium wilfordii Hook F on reproductive organs and hormones. Zhongguo Zhong Xi Yi Jie He Za Zhi 13:376–377 (in Chinese)

66.

Yu DY (1987) Experience in long term treatment of rheumatoid arthritis with Tripterygium wilfordii Hook. Jiangsu Yi Yao 12:661–662 (in Chinese)

Title: A Chinese herb Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis: mechanism, efficacy, and safety
Authors: Jun Bao
Sheng-Ming Dai
Publication date: 01-09-2011
Publisher: Springer-Verlag
Published in: Rheumatology International / Issue 9/2011
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-011-1841-y

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

A Chinese herb Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis: mechanism, efficacy, and safety

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2011

Quantification of regulatory T cells in peripheral blood of patients with systemic lupus erythematosus

Bronchoalveolar lavage in systemic sclerosis with lung involvement: role and correlations with functional, radiological and scintigraphic parameters

Osteomyelitis variolosa

Assessment of the relatives or spouses cohabiting with the fibromyalgia patients: is there a link regarding fibromyalgia symptoms, quality of life, general health and psychologic status?

Vitamin D may not be a good marker of disease activity in Korean patients with systemic lupus erythematosus

RF vs. anti-CCP: competitor or companion?

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page