Tripterygium wilfordii glycosides (often abbreviated as TWG or TG) are pharmaceutical preparations derived from the plant Tripterygium wilfordii. The production of these preparations involves extraction and purification of specific glycosidic compounds, primarily by means of column chromatography. The aim of these procedures is to enrich defined active constituents such as triptolide and celastrol while simultaneously reducing the concentration of toxic acidic compounds. However, Tripterygium wilfordii glycosides still contain a mixture of pharmacologically active and toxic components [1] [2] [3] [4]. Consequently, all studies in which Tripterygium glycosides were administered were excluded from the present analysis. In this work, only studies were considered in which Tripterygium wilfordii was applied as an extract of the whole thunder god vine plant and not as a mixture of different herbal substances.
In addition, all duplicate publications identified on the basis of the above-mentioned keywords were excluded. Ultimately, 13 studies were included in the analysis.
Tripterygium wilfordii, a medicinal plant used in traditional Chinese medicine, has attracted attention as a potential therapeutic option in rheumatoid arthritis (RA). The MMI Pharmindex lists, under the keyword “Tripterygium”, a single full-extract preparation that is marketed as a non-prescription dietary supplement.
Several systematic reviews and meta-analyses have documented its efficacy in the treatment of RA, particularly in comparison with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) such as methotrexate or sulfasalazine [5] [6] [7]. Across these analyses, Tripterygium wilfordii—both as monotherapy and in combination therapy—consistently led to significant improvements in clinical parameters such as the number of swollen and tender joints, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) [8] [9]. With regard to the ACR20 response rate, the documented superiority over sulfasalazine is particularly noteworthy [6]. In another study, an improvement in forced vital capacity was reported in patients with systemic sclerosis-associated interstitial lung disease treated with Tripterygium wilfordii [10]. No clinical trials, randomized controlled trials, or meta-analyses could be identified for other inflammatory rheumatic diseases.
Pharmacologically active constituents of Tripterygium wilfordii could potentially be used as an adjunct to csDMARD therapy in RA. It should be noted that preparations containing Tripterygium wilfordii glycosides have been successfully evaluated in the treatment of RA in some studies; however, these preparations are neither approved nor available in Germany.
Publications by Lv et al. and Zhou et al. report that adverse events occurred in 46.4–48% of treated RA patients [11] [8]. Reported adverse events include hepatic dysfunction with elevated liver enzymes (9.6–11.5%), abdominal complaints (29.0%) with nausea (13–22%), vomiting (15%), diarrhea (25%), dyspepsia (22%), abdominal pain (18%), upper respiratory tract infections (1.9–18%), menstrual disturbances (5.0–12.5%), and skin rash (12%) [12] [13] [11] [8].
A critical appraisal of the clinical findings of the aforementioned studies is warranted. The majority of trials were based on relatively soft endpoints, most notably the ACR20 response [7] [5, 8], which reflects only a 20% improvement in clinical parameters and inflammatory markers and must therefore be considered a weak endpoint. More robust endpoints such as ACR50, ACR70, or complete remission (e.g. defined by DAS28 < 2.6) were reported only in isolated cases or were not used as primary endpoints [9]. Imaging-based assessment of radiographic progression was performed in only a single long-term study, which further limits the generalizability to routine clinical practice.
Another major limitation is the absence of head-to-head comparison studies with modern therapies, in particular biological DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs). It therefore remains unclear whether Tripterygium wilfordii is equivalent or superior to these agents in terms of efficacy.
Tripterygium wilfordii may possess therapeutic potential in RA; however, the available evidence is limited by substantial methodological shortcomings, including the predominant use of weak endpoints and the lack of comparisons with modern treatment options. No approved preparation with a defined content of active ingredients is currently available in Germany. Use of Tripterygium wilfordii may be associated with adverse drug reactions, particularly hepatic dysfunction and gastrointestinal complaints. Its use as a dietary supplement with the intention of alleviating musculoskeletal symptoms is not recommended.
1. Fang W, Peng F, Yi T, Zhang C, Wan C, Xu H, Lam CW, Yang X: Biological activity and safety of Tripterygium extract prepared by sodium carbonate extraction. Molecules 2012, 17(9):11113-11123.
2. Du X, Nyagblordzro M, An L, Gao X, Du L, Wang Y, Ondieki G, Kikete S, He X: Pharmacokinetic and Toxicological Characteristics of Tripterigium Glycosides and Their Derivatives. Curr Drug Metab 2018, 19(7):605-627.
3. Wu W, Cheng R, Boucetta H, Xu L, Pan JR, Song M, Lu YT, Hang TJ: Differences in Multicomponent Pharmacokinetics, Tissue Distribution, and Excretion of Tripterygium Glycosides Tablets in Normal and Adriamycin-Induced Nephrotic Syndrome Rat Models and Correlations With Efficacy and Hepatotoxicity. Front Pharmacol 2022, 13:910923.
4. Qian Q, Gao Y, Xun G, Wang X, Ge J, Zhang H, Mou F, Su S, Wang Q: Synchronous Investigation of the Mechanism and Substance Basis of Tripterygium Glycosides Tablets on Anti-rheumatoid Arthritis and Hepatotoxicity. Appl Biochem Biotechnol 2022, 194(11):5333-5352.
5. Wang HL, Jiang Q, Feng XH, Zhang HD, Ge L, Luo CG, Gong X, Li B: Tripterygium wilfordii Hook F versus conventional synthetic disease-modifying anti-rheumatic drugs as monotherapy for rheumatoid arthritis: a systematic review and network meta-analysis. BMC Complement Altern Med 2016, 16:215.
6. Luo Y, Hou X, Xi A, Luo M, Wang K, Xu Z: Tripterygium wilfordii Hook F combination therapy with methotrexate for rheumatoid arthritis: An updated meta-analysis. J Ethnopharmacol 2023, 307:116211.
7. Cameron M, Gagnier JJ, Chrubasik S: Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev 2011(2):Cd002948.
8. Zhou YZ, Zhao LD, Chen H, Zhang Y, Wang DF, Huang LF, Lv QW, Liu B, Li Z, Wei W et al: Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study. Arthritis Res Ther 2018, 20(1):70.
9. Tao X, Younger J, Fan FZ, Wang B, Lipsky PE: Benefit of an extract of Tripterygium Wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study. Arthritis Rheum 2002, 46(7):1735-1743.
10. Yang L, Wang Q, Hou Y, Zhao J, Li M, Xu D, Zeng X: The Chinese herb Tripterygium wilfordii Hook F for the treatment of systemic sclerosis-associated interstitial lung disease: data from a Chinese EUSTAR Center. Clin Rheumatol 2020, 39(3):813-821.
11. Goldbach-Mansky R, Wilson M, Fleischmann R, Olsen N, Silverfield J, Kempf P, Kivitz A, Sherrer Y, Pucino F, Csako G et al: 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, w249-251.
12. Jiang M, Zha Q, Zhang C, Lu C, Yan X, Zhu W, Liu W, Tu S, Hou L, Wang C et al: Predicting and verifying outcome of Tripterygium wilfordii Hook F. based therapy in rheumatoid arthritis: from open to double-blinded randomized trial. Sci Rep 2015, 5:9700.
13. Lv QW, Zhang W, Shi Q, Zheng WJ, Li X, Chen H, Wu QJ, Jiang WL, Li HB, Gong L et al: Comparison of Tripterygium wilfordii Hook F with methotrexate in the treatment of active rheumatoid arthritis (TRIFRA): a randomised, controlled clinical trial. Ann Rheum Dis 2015, 74(6):1078-1086.
14. 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.
15. Cameron M, Gagnier JJ, Little CV, Parsons TJ, Blümle A, Chrubasik S: Evidence of effectiveness of herbal medicinal products in the treatment of arthritis. Part 2: Rheumatoid arthritis. Phytother Res 2009, 23(12):1647-1662.
16. Cibere J, Deng Z, Lin Y, Ou R, He Y, Wang Z, Thorne A, Lehman AJ, Tsang IK, Esdaile JM: A randomized double blind, placebo controlled trial of topical Tripterygium wilfordii in rheumatoid arthritis: reanalysis using logistic regression analysis. J Rheumatol 2003, 30(3):465-467.
Appendix 1
Assessment of the evidence base: design of the PubMed search.
A PubMed search was conducted using the keywords listed in the table below. For the search terms “tripterygium wilfordii rheumatic or tripterygium wilfordii arthritis” and “tripterygium wilfordii and connective tissue disease,” 521 search results were initially identified. The search was restricted to the terms “Clinical Trial,” “Meta-Analysis,” “Randomized Controlled Trial,” and “English language.”
| Keywords | References identified in PubMed |
|---|---|
| tripterygium wilfordii rheumatic or tripterygium wilfordii arthritis | n = 30 |
| tripterygium wilfordii and vasculitis rheumatic | n = 0 |
| tripterygium wilfordii and connective tissue dissease | n = 28 |
| tripterygium wilfordii rheumatioid arthritis | n = 30 |
| tripterygium wilfordii and psoriatic arthritis | n = 0 |
| tripterygium wilfordii and spondyloarthritis | n = 0 |
| tripterygium wilfordii and systemic sclerosis | n = 1 |
| tripterygium wilfordii and sharp syndrome | n = 0 |
| tripterygium wilfordii and lupus | n = 0 |
| tripterygium wilfordii and giant cell arteriitis | n = 0 |
| tripterygium wilfordii and temporalis arteriitis | n = 0 |
| tripterygium wilfordii and panarteriitis nodosa | n = 0 |
| tripterygium wilfordii and granulomatosis with polyangiitis | n = 0 |
| tripterygium wilfordii and microscopic polyangiitis | n = 0 |
| tripterygium wilfordii and eosinophlic granulomatosis with polyangiitis | n = 0 |
Appendix 2
Overview of the evaluated publications.
| Publication | Cohort | Results |
|---|---|---|
| Wang HL et al. [5] |
|
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| Luo et al. [6] |
|
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| Wang X et al. [14] |
|
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| Cameron M et al. [7] |
|
|
| Zhou YZ et al. [8] |
|
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| Goldbach-Mansky R et al. [11] |
|
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| Lv QW et al. [13] |
|
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| Jiang M et al. [12] |
| ACR20 response
|
| Tao X et al. [9] |
| ACR20 response
|
| Cameron et al. [15] |
|
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| Cibere J et al. [16] |
| ACR20 response
|
| Tao X et al. [9] |
|
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| Yang L et al. [10] |
|
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Last updated: March 11, 2026