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Scientific Name(s): Tripterygium wilfordii Hook.
Common Name(s): Early rice flower, Huang-t’eng ken, Lei gong teng, Lei-kung t’eng, Thunder god vine, Thunder of god vine, Tsao-ho-hua, Yellow vine root
Medically reviewed by Holevn.org. Last updated on Jun 1, 2018.
Clinical Overview
Use
Thunder god vine has primarily been evaluated for use in rheumatoid arthritis (RA) and ankylosing spondylitis; however, its adverse event profile and limited quality trials restrict any recommendations for clinical use. Antifertility properties in men have been described, while amenorrhea was observed in women.
Dosing
Clinical trials have evaluated lower (60 mg daily) to higher doses (180 to 350 mg daily) of T. wilfordii for the treatment of RA.
Doses of 20 to 30 mg/day of a refined extract of T. wilfordii (one-third the usual recommended dose for RA) for 1.5 to 5 months has produced antifertility effects in men.
Contraindications
Contraindications have not been identified. Due to immune suppression, thunder god vine preparations should not be used in immunocompromised patients.
Pregnancy/Lactation
Avoid use. Embryotoxicity has been demonstrated in mice.
Interactions
None well documented.
Adverse Reactions
Clinically important adverse events have been reported in clinical trials. GI upset, male and female infertility, and immune suppression are common adverse effects of thunder god vine.
Toxicology
Information is limited.
Scientific Family
- Celastraceae
Botany
Tripterygium is a woody perennial twining vine native to parts of China, Korea, Japan, and Taiwan and usually found growing close to water sources. It has reddish-brown branches with oval leaves. In the summer, small white terminal flowers bloom. Some disagreement regarding taxonomy of related species exists.Brinker 2007, Canter 2006
History
Thunder god vine has been used for centuries in traditional Chinese medicine to treat fever, boils, abscesses, and inflammation, and also as an immunosuppressive agent to decrease proteinuria and preserve kidney function. Preparations of Tripterygium have been used since the 1960s in China to treat RA and inflammation; however, toxicity concerns limited use to a hot water decoction. Attempts have been made to limit the toxicity through different extraction methods and by using only the less toxic portion of the plant root. It has also been used as an insecticide and as rat and bird poison.Brinker 2007, Li 1990 T. wilfordii glycosides are a patented Chinese traditional medicine that are approved by the China State Food and Drug Administration for autoimmune and inflammatory diseases.Wang 2017
Chemistry
The major constituent isolated from thunder god vine roots is diterpenoid triptolide. Other constituents, some of which may be pharmacologically as important as triptolide, include sesquiterpenes (eg, dihydroagarofurans, alkaloids), diterpenes (eg, tripdiolide, tripchlorolide), and triterpenes. The quinone triterpene celastrol has been described and may possess immune, inflammatory, and chemotherapeutic properties.Kannaiyan 2011 Methods of extraction include aqueous and ethanol processes.Brinker 2007, Canter 2006
Uses and Pharmacology
Antifertility effects
Clinical data
An antifertility effect was observed in men participating in a study to evaluate the effect of T. wilfordii in RA. Mean sperm density and motility were lower in the treatment arm (20 to 30 mg of extract per day) versus control. Follicle-stimulating hormone was higher in the treatment group; however, testosterone levels and libido appeared unaffected.Lopez 2005 Similar observations have been reported for a related species. These observations led to the extraction and further evaluation of the chemical constituent triptolide and other compounds as potential male contraceptive agents. These compounds appear to act primarily on sperm development (eg, sperm head-tail separation) rather than affecting testosterone levels, with sperm returning to normal after 6 weeks.Lopez 2005, Lue 1998, Matlin 1993, Qian 1987, Zhen 1995 High-quality clinical trials are lacking to confirm efficacy or safety.
Antitumor activity
Reviews of potential applications for T. wilfordii in cancer have been published.Liu 2011, Wong 2012, Ziaei 2016
Animal data
Low doses of the diterpene triptolide showed antileukemic and antitumor activity in rodents, while demethylzeylasteral demonstrated antiangiogenic properties.Shamon 1997, Ushiro 1997, Xu 1992
Clinical data
In a study of RA patients, effects of thunder god vine on TNF produced by peripheral blood mononuclear cells and synovium cells have been reported.Zeng 1996
Antiviral activity
In vitro data
Neotripterifordin showed potent anti-HIV replication activity in vitro.Chen 1992, Chen 1995 Triptofordin C-2 and other sesquiterpene components of thunder god vine have been evaluated for their antiviral activity, including activity against human cytomegalovirus.Hayashi 1996
CNS
Animal and in vitro data
Animal models have demonstrated anti-inflammatory protective activity on dopamine neurons by triptolide and trichlorolide.Brinker 2007, Chen 2007, Li 2004
Immunomodulatory
Animal data
Animal studies and in vitro models have shown thunder god vine exerts effects in autoimmune diseases. Inflammatory cytokines interleukin 6 (IL-6), IL-1beta, and tumor necrosis factor alpha (TNF-alpha) decreased, while a concomitant increase occurred in anti-inflammatory cytokine IL-37. This increase may be due to action on the ERK1/2 or p38 MAPK signalling pathways.Wang 2017 Interference in cytokine transcription, response of mononuclear cells, generation of cytotoxic T-cells, prostaglandin secretion, IL-2 production, IL-37 protein upregulation, and inhibition of T-cell and B-cell proliferation are among other suggested mechanisms.Chang 1997, Li 1990, Sylvester 2001, Tao 1991, Wang 2017, Ye 1990 Involvement of the major inflammation signaling pathways, ERK1/2 and p38 MAPK, in the upregulation of IL-37 induced by T. wilfordii has also been documented.Wang 2017 The major immunosuppressive activity is considered to be due to the diterpenoids triptolide and tripdiolide.Canter 2006, Tao 1995 Other chemical compounds may also be involved.Bao 2011
Clinical data
Few methodologically sound clinical trials have been conducted. Some lack randomization or a control or comparator group, and in some, the preparation is used in combination with other agents.Bao 2011, Cameron 2011 A Cochrane review of clinical trials conducted up to 2010 and meeting quality criteria concluded that T. wilfordii may improve some symptoms of RA.Cameron 2011
Systematic reviews report a lack of evidence of efficacy for T. wifordii in RA, based on methodologically weak clinical trials.Liu 2013, Macfarlane 2011 Other reviews of trials of better quality and inclusion criteria support T. wilfordii.Wang 2016
Improvements in both patient- and physician-rated tenderness, swelling, and morning stiffness were demonstrated in 3 studies. Laboratory indices of RA, including erythrocyte sedimentation rate, immunoglobulin G (IgG), IgM, IgA, and C-reactive protein also improved.Goldbach-Mansky 2009, Tao 1989, Tao 2002 A meta-analysis of tripterygium glycosides in the treatment of ankylosing spondylitis included 11 moderate-quality, randomized clinical trials (N=807) and reported an odds ratio in favor of standard therapy over tripterygium glycosides tablets for overall symptom improvement (0.46 [95% CI, 0.24 to 0.9]). Tripterygium glycosides tablets also did not improve morning stiffness or other indices.Li 2015
Remission of a rare case of the auto-inflammatory condition SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome has been reported. A 57-year-old Chinese woman exhibited marked improvement in symptoms after 1 month of T. wilfordii that, within 4 months of treatment, led to complete resolution of bone marrow edema. The starting dose was 20 mg 3 times daily and was reduced gradually to 20 mg every 3 months. No adverse events were noted.Chen 2007
Renal effects
Animal data
Animal and in vitro models have shown thunder god vine possesses immunosuppressive effects.Li 1990
Clinical data
A Cochrane review of clinical trials evaluating T. wilfordii in nephrotic syndrome included 10 studies dating up to 2012 (N=630). Quality limitations prevented a meta-analysis of the data. Mostly T. wilfordii is used in combination with other immunosuppressive agents, and, consequently, the reported effects cannot be substantiated for T. wilfordii alone.Chen 2013
Clinically important nephrotoxicity with use of thunder god vine, which may be dose related, has been reported in the literature.Brown 2017, Rahman 2017
Dosing
Clinical trials have evaluated lower (60 mg daily) to higher doses (180 to 350 mg daily) of T. wilfordii for the treatment of RA.Cameron 2011
Few long-term studies have used T. wilfordii 1 mg/kg/day for up to 5 years to evaluate effects in renal transplant recipients; however, adequate safety data during that time period are limited.Ji 2006, Ji 2008
In a study of men with RA, 20 to 30 mg/day of a refined extract of T. wilfordii (one-third the usual recommended dose for RA) for 1.5 to 5 months produced antifertility effects.Lopez 2005
Pregnancy / Lactation
Avoid use. Embryotoxicity occurred in mice fed an aqueous extract of T. wilfordii and included neural effects, absence of limb buds, and ophthalmic-related effects.Chan 1995 Amenorrhea has been reported in women participating in clinical trials.Bao 2011, Canter 2006, Ji 2008
Interactions
None well documented. Because high doses of T. wilfordii may suppress immune function, a theoretical additive effect when used in combination with immunosuppressive medications (eg, azathioprine, corticosteroids) may occur.Rahman 2017
Adverse Reactions
Clinically important adverse events, including cardiovascular-related death and renal failure, have been reported, particularly at higher dosages.Allard 2013, Brown 2017, Rahman 2017
GI upset (ie, nausea, abdominal pain, indigestion, flatulence, constipation, diarrhea), male and female infertility, and immune suppression are common adverse effects of thunder god vine. Hair loss, skin rash, and blisters have also been reported.Canter 2006, Ji 2006, Little 2001, Lopez 2005
In rats, dose-dependent negative effects on male reproductive organs and tissues, testosterone levels, cholesterol levels, cholesterol-to-testosterone conversion rate, and total body weight have been observed. Some effects were observed within 4 weeks of administration. The mechanism involved significant downregulation of genes for proteins and key enzymes needed for testosterone synthesis.Jing 2017
Toxicology
Information is limited; however, one case report describes an incidence of death in a young and seemingly healthy male 3 days postingestion of T. wilfordii. Later investigation found some incidence of coexisting cardiac damage.Chou 1995
Treatments involving high doses of triptolide (eg, 50 mcg per mouse 3 times weekly) in one study were lethal.Shamon 1997
Embryotoxicity occurred in mice fed an aqueous extract of T. wilfordii for 10 days, and included neural effects, absence of limb buds, and ophthalmic-related effects.Chan 1995
References
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Phytomedicine. 2006;13(5):371-377.16487688Chan WY, Ng TB. Adverse effect of Tripterygium wilfordii extract on mouse embryonic development. Contraception. 1995;51(1):65-71.7750287Chang DM, Chang WY, Kuo SY, Chang ML. The effects of traditional antirheumatic herbal medicines on immune response cells. J Rheumatol. 1997;24(3):436-441.9058645Chen K, Shi QA, Fujioka T, et al. Anti-AIDS agents, 4. Tripterifordin, a novel anti-HIV principle from Tripterygium wilfordii: isolation and structural elucidation. J Nat Prod. 1992;55(1):88-92.1602302Chen K, Shi Q, Fujioka T, et al. Anti-AIDS agents—XIX. Neotripterifordin, a novel anti-HIV principle from Tripterygium wilfordii: isolation and structural elucidation. Bioorg Med Chem. 1995;3(10):1345-1348.8564400Chen LW, Wang YQ, Wei LC, Shi M, Chan YS. Chinese herbs and herbal extracts for neuroprotection of dopaminergic neurons and potential therapeutic treatment of Parkinson’s disease. 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Transplant Proc. 2006;38(5):1274-1279.16797280Ji SM, Li LS, Wen JQ, et al. Therapeutic effect of Tripterygium wilfordii on proteinuria associated with sirolimus in renal transplant recipients. Transplant Proc. 2008;40(10):3474-3478.19100416Jing X, Cheng W, Guo S, Zou Y, Zhang T, He L. Toxic effects of Tripterygium wilfordii Hook F on the reproductive system of adolescent male rats. Biomed Pharmacother. 2017;95:1338-1345.28938525Kannaiyan R, Shanmugam MK, Sethi G. Molecular targets of celastrol derived from Thunder of God Vine: potential role in the treatment of inflammatory disorders and cancer. Cancer Lett. 2011;303(1):9-20.21168266Li XW, Weir MR. Radix Tripterygium wilfordii—a Chinese herbal medicine with potent immunosuppressive properties. Transplantation. 1990;50(1):82-86.2368155Li FQ, Lu XZ, Liang XB, et al. Triptolide, a Chinese herbal extract, protects dopaminergic neurons from inflammation-mediated damage through inhibition of microglial activation. J Neuroimmunol. 2004;148(1-2):24-31.14975583Li H, Guo F, Luo YC, Zhu JP, Wang JL. Efficacy of tripterygium glycosides tablet in treating ankylosing spondylitis: a systematic review and meta-analysis of randomized controlled trials. Clin Rheumatol. 2015;34(11):1831-1838.26255190Little CV, Parsons T. Herbal therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2001;(1):CD002947.11279783Liu Z, Ma L, Zhou GB. The main anticancer bullets of the Chinese medicinal herb, thunder god vine. Molecules. 2011;16(6):5283-5297.21701438Liu Y, Tu S, Gao W, et al. Extracts of Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis: a systemic review and meta-analysis of randomised controlled trials. Evid Based Complement Alternat Med. 2013;2013:410793.24391674Lopez LM, Grimes DA, Schulz KF. Nonhormonal drugs for contraception in men: a systematic review. Obstet Gynecol Surv. 2005;60(11):746-752.16250923Lue Y, Sinha Hikim AP, Wang C, et al. 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Evaluation of the mutagenic, cytotoxic, and antitumor potential of triptolide, a highly oxygenated diterpene isolated from Tripterygium wilfordii. Cancer Lett. 1997;112(1):113-117.9029176Sylvester J, Liacini A, Li WQ, Dehnade F, Zafarullah M. 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-kappaB activities. Mol Pharmacol. 2001;59(5):1196-1205.11306704Tao XL, Sun Y, Dong Y, et al. A prospective, controlled, double-blind, cross-over study of Tripterygium wilfordii hook F in treatment of rheumatoid arthritis. Chin Med J (Engl). 1989;102(5):327-332.2509153Tao 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):1274-1281.1930317Tao X, Cai JJ, Lipsky PE. The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract (T2) of Tripterygium wilfordii Hook. F. J Pharmacol Exp Ther. 1995;272(3):1305-1312.7891348Tao 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):1735-1743.12124856Ushiro S, Ono M, Nakayama J, et al. New nortriterpenoid isolated from anti-rheumatoid arthritic plant, Tripterygium wilfordii, modulates tumor growth and neovascularization. Int J Cancer. 1997;72(4):657-663.9259407Xu JY, Yang J, Li LZ. Antitumor effect of Tripterygium wilfordii [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1992;12(3):161-164, 134.1504534Wang HL, Jiang Q, Feng XH, et al. 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;16:215.27411429Wang S, Li R, He S, et al. Tripterygium wilfordii glycosides upregulate the new anti-inflammatory cytokine IL-37 through ERK1/2 and p38 MAPK signal pathways. Evid Based Complement Alternat Med. 2017;2017:9148523.29403538Wong KF, Yuan Y, Luk JM. Tripterygium wilfordii bioactive compounds as anticancer and anti-inflammatory agents. Clin Exp Pharmacol Physiol. 2012;39(3):311-320.21834865Ye WH. Mechanism of treating rheumatoid arthritis with polyglycosides of Tripterygium wilfordii Hook (T II). III. Study on inhibitory effect of T II on in vitro Ig secreted by peripheral blood mononuclear cells from normal controls and RA patients [in Chinese]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1990;12(3):217-222.2150359Zeng X, Zhang N. 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