Tripterygium wilfordii / Thunder god vine

Common Names:  
thunder god vine, lei gong teng
Latin Name: Tripterygium wilfordii

Thunder god vine is a perennial vine native to China, Japan, and Korea. It has been used in China for health purposes for more than 400 years. In traditional Chinese medicine, it has been used for conditions involving inflammation or overactivity of the immune system. Currently, thunder god vine is used as a traditional or folk remedy for excessive menstrual periods and autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, and lupus.

Extracts are prepared from the skinned root of thunder god vine.

What the Science Says
Laboratory findings suggest that thunder god vine may fight inflammation, suppress the immune system, and have anti-cancer effects.
Although early evidence is promising, there have been few high-quality studies of thunder god vine in people. Results from a large study funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), which compared an extract of thunder god vine root with a conventional medicine (sulfasalazine) for rheumatoid arthritis, found that participants’ symptoms (e.g., joint pain and swelling, inflammation) improved more significantly with thunder god vine than with sulfasalazine.
A small study on thunder god vine applied to the skin found benefits for rheumatoid arthritis symptoms.
There is not enough scientific evidence to assess thunder god vine’s use for any other health conditions.

Side Effects and Cautions
Thunder god vine can cause severe side effects and can be poisonous if it is not carefully extracted from the skinned root. Other parts of the plant—including the leaves, flowers, and skin of the root—are highly poisonous and can cause death.
A number of participants in the NIAMS study experienced gastrointestinal adverse effects such as diarrhea, indigestion, and nausea, as well as upper respiratory tract infections. (The rate of adverse effects was similar in the thunder god vine and sulfasalazine groups.)
Thunder god vine can also cause hair loss, headache, menstrual changes, and skin rash.
There are no consistent, high-quality thunder god vine products being manufactured in the United States. Preparations of thunder god vine made outside the United States (for example, in China) can sometimes be obtained, but it is not possible to verify whether they are safe and effective.
Thunder god vine has been found to decrease bone mineral density in women who take the herb for 5 years or longer. This side effect may be of particular concern to women who have osteoporosis or are at risk for the condition.
Thunder god vine contains chemicals that might decrease male fertility by changing sperm.
Tell all your health care providers about any complementary health practices you use. Give them a full picture of what you do to manage your health. This will help ensure coordinated and safe care. For tips about talking with your health care providers about complementary and alternative medicine, see NCCAM's Time to Talk campaign.
Search the scientific literature for potential herb-drug interactions

Sources
  • Canter PH, Hyang SL, Ernst E. A systematic review of randomized clinical trials of Tripterygium wilfordii for rheumatoid arthritis. Phytomedicine. 2006;13(5):371–377.
  • Carter BZ, Mark DH, Schober WD, et al. Triptolide induces caspase-dependent cell death mediated via the mitochondrial pathway in leukemic cells. Blood. 2006;108(2):630–637.
  • Goldbach-Manksy R, Wilson M, Fleischmann R, et al. Comparison of Tripterygium wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis: a randomized trial. Annals of Internal Medicine. 2009;151(4):229–240, W49–51.
  • National Center for Complementary and Alternative Medicine. Rheumatoid Arthritis and CAM. National Center for Complementary and Alternative Medicine Web site. Accessed at nccam.nih.gov/health/RA/getthefacts.htm on June 3, 2010.
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases. Chinese Thunder God Vine Gives Relief from Rheumatoid Arthritis Symptoms. National Institute of Arthritis and Musculoskeletal and Skin Diseases Web site. Accessed at www.niams.nih.gov/News_and_Events/Spotlight_on_Research/2002/thunder.asp on June 3, 2010.
  • Setty AR, Sigal LH. Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects. Seminars in Arthritis and Rheumatism. 2005;34(6):773–784.
  • Tao X, Younger J, Fan FZ, et al. Benefit of an extract of Tripterygium wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study. Arthritis & Rheumatism. 2002;46(7):1735–1743.
  • Thunder god vine. Natural Medicines Comprehensive Database Web site. Accessed at www.naturaldatabase.com on September 15, 2009.

Phytomedicine. 2006 May;13(5):371-7. Epub 2006 Feb 17. A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid arthritis. Canter PH, Lee HS, Ernst E.
Complementary Medicine, Peninsula Medical School, Universities of Exeter & Plymouth, 25 Victoria Park Rd, Exeter, Devon EX2 4NT, UK. peter.canter@pms.ac.uk

Tripterygium wilfordii is a Chinese herb with immunosuppressive effects and an established history of use in the treatment of rheumatoid arthritis (RA). We have carried out a systematic review of randomised clinical trials (RCTs) which assess the effectiveness of T. wilfordii in this indication. We included only randomised and controlled studies which tested the effectiveness of T. wilfordii monopreparations in the treatment of RA. Studies in any language were included. A search of five electronic databases from inception to February 2005 identified 18 articles which could potentially meet our inclusion criteria. Only 16 of these could be retrieved from the scientific literature and after reading these in full, only two unique RCTs meeting our inclusion criteria were identified. Both indicated that T. wilfordii has beneficial effects on the symptoms of RA. However, the literature indicates that T. wilfordii is associated with serious adverse events which make the risk-benefit analysis for this herb unfavourable. Therefore, we cannot recommend its use.



Tripterygium is a woody perennial twining vine native to parts of China, Korea, Japan, and Taiwan, and is usually found growing close to water sources. It has reddish-brown branches with oval leaves. In the summer, small white terminal flowers bloom. Some disagreements about the taxonomy of related species exist. 1 , 2


History
The thunder god vine has been used for centuries in traditional Chinese medicine to treat fever, boils, abscesses, and inflammation. Preparations of Tripterygium have been used since the 1960s in China to treat RA and inflammation; however, toxicity concerns limited its 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. 1

Chemistry
The major constituent isolated from thunder god vine roots has been identified as the 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. Methods of extraction include aqueous and ethanol processes. 1 , 2

Thunder God Vine Uses and Pharmacology

Antifertility
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. 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; however, high quality clinical trials are lacking to confirm efficacy or safety. 3 , 4 , 5 , 6 , 7

Renal effects
Limited clinical trials have demonstrated positive effects of extracts in renal-associated conditions, such as renal transplant and idiopathic refractory nephrotic syndrome, although the effects may be largely due to immune-modulation rather than direct activity on the kidney. One trial evaluated the effect of T. wilfordii in renal transplant recipients over 5 years; however, there did not appear to be any randomization or blinding in the study. 8 In a study lasting longer than 1 year, the same group of researchers evaluated the effect on sirolimus-induced proteinuria in similar patients. 9 Three trials included in a meta-analysis on idiopathic refractory nephrotic syndrome showed beneficial effects on laboratory indices such as proteinuria, hypoalbuminemia, edema, and hypercholesterolemia. 10

Rheumatoid arthritis
Animal and human studies, as well as in vitro models, have shown thunder god vine to exert effects in autoimmune diseases. Interference in cytokine transcription, response of mononuclear cells, generation of cytotoxic T-cells, prostaglandin secretion, IL-2 production, and inhibition of T-cell and B-cell proliferation are among the suggested mechanisms. 11 , 12 , 13 , 14 , 15 The major immunosuppressive activity is due to the diterpenoids triptolide and tripdiolide. 2 , 16 Other chemical compounds may also be involved. 17 , 18

Few clinical trials have been conducted that are methodologically sound. In some, there is no randomization, in others, no control group or comparator, and in some, the preparation is used in combination with other agents. However, in those few that do meet quality criteria, T. wilfordii possessed beneficial effects on RA symptoms and clinically important adverse events. 2 , 19 , 20

Improvements in both patient- and physician-rated tenderness, swelling, and morning stiffness have been demonstrated. Laboratory indices of the disease, including erythrocyte sedimentation rate, immunoglobulin G, immunoglobulin M, immunoglobulin A, and C-reactive protein also improved. 2 , 20 , 21 , 22 A trial conducted among US participants in 2005 found a greater effect for a T. wilfordii extract than sulfasalazine in treating RA over 24 weeks, with similar adverse event rates. 23

Antiviral
Neotripterifordin showed potent anti-HIV replication activity in vitro. 24 , 25 Triptofordin C-2 and other sesquiterpene components of thunder god vine have been evaluated for their antiviral activity, including activity against human cytomegalovirus. 26

Antitumor
Low doses of the diterpene triptolide showed antileukemic and antitumor activity in rodents; while demethylzeylasteral demonstrated antiangiogenic properties. 27 , 28 , 29 Effects of thunder god vine on tumor necrosis factor have been reported. 30

CNS
Animal models have been used to demonstrate anti-inflammatory protective action on dopamine neurons by triptolide and trichlorolide. Clinical studies are lacking. 1 , 31 , 32

Dosage
  • In RA trials, 60 mg/day of T2 (a chloroform-methanol extract of T. wilfordii ) for 12 weeks has been evaluated, as well as ethanol/ethyl alcohol root extract 180 to 360 mg/day. 2 , 21 , 22
  • Few long-term studies have evaluated the use of 1 mg/kg/day of T2 for up to 5 years; however, adequate safety data during the same time period are limited. 8 , 9
  • The effective antifertility dose has been suggested at one-third the recommended dose for treatment of arthritis; however, quality clinical trials are lacking to confirm efficacy and safety. 3

Pregnancy/Lactation
Avoid use. Embryotoxicity was demonstrated in mice fed an aqueous extract of T. wilfordii and included neural effects, absence of limb buds, and ophthalmic-related effects. 33 Amenorrhea is reported among women participating in clinical trials. 2 , 9

Interactions
None well documented.

Adverse Reactions
Clinically important adverse events have been reported in clinical trials.
GI upset (including nausea, abdominal pain, indigestion, flatulence, constipation, and 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. 2 , 3 , 8 , 19

Toxicology

Information is limited; however, one case report describes an incidence of death in a seemingly young and healthy male 3 days postingestion of the drug. Later investigation found some incidence of coexisting cardiac damage. 34 Treatments of 50 mcg per mouse 3 times weekly in one preparation were lethal. 27
Embryotoxicity was demonstrated in mice fed an aqueous extract of T. wilfordii for 10 days, and included neural effects, absence of limb buds, and ophthalmic-related effects. 33

Bibliography
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2. Canter PH, Lee HS, Ernst E. A systematic review of randomised clinical trials of Tripterygium wilfordii for rheumatoid arthritis. Phytomedicine . 2006;13(5):371-377.
3. Lopez LM, Grimes DA, Schulz KF. Nonhormonal drugs for contraception in men: a systematic review. Obstet Gynecol Surv . 2005;60(11):746-752.
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6. Matlin SA, Belenguer A, Stacey VE, et al. Male antifertility compounds from Tripterygium wilfordii Hook f. Contraception . 1993;47(4):387-400.
7. Qian SZ. Tripterygium wilfordii , a Chinese herb effective in male fertility regulation. Contraception . 1987;36(3):335-345.
8. Ji SM, Wang QW, Chen JS, Sha GZ, Liu ZH, Li LS. Clinical trial of Tripterygium wilfordii Hook F. in human kidney transplantation in China. Transplant Proc . 2006;38(5):1274-1279.
9. Ji 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.
10. Xu G, Tu W, Jiang D, Xu C. Tripterygium wilfordii Hook F treatment for idiopathic refractory nephrotic syndrome in adults: a meta-analysis. Nephron Clin Pract . 2009;111(4):c223-c228.
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14. Ye 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.
15. Sylvester 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.
16. Tao 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.
17. Tamaki T, Kawamura A, Komatsu Y, Kawamura H, Maruyama H, Morota T. Phenolic nortriterpene demethylzeylasteral: a new immunosuppressive component of Tripterygium wilfordii Hook f. Transplant Proc . 1996;28(3):1379-1380.
18. Yu DQ, Zhang DM, Wang HB, Liang XT. Structure modification of triptolide, a diterpenoid from Tripterygium wilfordii [in Chinese]. Yao Xue Xue Bao . 1992;27(11):830-836.
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22. 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.
23. Goldbach-Mansky R, Wilson M, Fleischmann R, 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, W49-W51.
24. Chen 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.
25. Chen K, Shi Q, 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.
26. Hayashi K, Hayashi T, Ujita K, Takaishi Y. Characterization of antiviral activity of a sesquiterpene, triptofordin C-2. J Antimicrob Chemother . 1996;37(4):759-768.
27. Shamon LA, Pezzuto JM, Graves JM, et al. 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.
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29. Ushiro 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.
30. Zeng X, Zhang N. The effects of a single active ingredient (T4) of Tripterygium wilfordii Hook on the production of tumor necrosis factor by the peripheral blood mononuclear cells and synovium cells of rheumatoid arthritis patients [in Chinese]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao . 1996;18(2):138-142.
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33. Chan WY, Ng TB. Adverse effect of Tripterygium wilfordii extract on mouse embryonic development. Contraception . 1995;51(1):65-71.
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