Thunder God Vine

Scientific Name(s): Tripterygium wilfordii Hook. Family: Celastraceae

Common Name(s): Huang-t'eng ken ( yellow vine root ), lei-kung t'eng , lei gong teng (Chinese), thunder god vine , thunder of god vine , tsao-ho-hua ( early rice flower )

Uses

Thunder god vine has been evaluated for use primarily in rheumatoid arthritis (RA); 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

In RA trials, 60 mg/day of T2 (a chloroform-methanol extract of Tripterygium wilfordii ) for 12 weeks has been evaluated, as well as ethanol/ethyl alcohol root extract 180 to 360 mg/day. Several 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.

Contraindications

Contraindications have not been determined. Due to immune suppression, thunder god vine preparations should not be used in immune-compromised 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 side effects of thunder god vine.

Toxicology

Information is limited. Embryotoxicity was demonstrated in mice, including neural effects, absence of limb buds, and ophthalmic-related effects.

Botany

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

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

Other effects
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

1. Brinker AM, Ma J, Lipsky PE, Raskin I. Medicinal chemistry and pharmacology of genus Tripterygium ( Celastraceae ) [published correction appears in Phytochemistry . 2007;68(13):1819]. Phytochemistry . 2007;68(6):732-766.
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.
4. Lue Y, Sinha Hikim AP, Wang C, et al. Triptolide: a potential male contraceptive. J Androl . 1998;19(4):479-486.
5. Zhen Q, Ye X, Wei ZJ. Recent progress in research on Tripterygium : a male antifertility plant. Contraception . 1995;51(2):121-129.
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.
11. Li XW, Weir MR. Radix Tripterygium wilfordii —a Chinese herbal medicine with potent immunosuppressive properties. Transplantation . 1990;50(1):82-86.
12. Chang 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.
13. Tao 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.
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.
19. Little CV, Parsons T. Herbal therapy for treating osteoarthritis. Cochrane Database Syst Rev . 2001;(1):CD002947. 10.1002/14651858.CD002948 .
20. 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.
21. Tao 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.
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.
28. Xu 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.
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.
31. Chen 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. CNS Neurol Disord Drug Targets . 2007;6(4):273-281.
32. Li 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.
33. Chan WY, Ng TB. Adverse effect of Tripterygium wilfordii extract on mouse embryonic development. Contraception . 1995;51(1):65-71.
34. Chou WC, Wu CC, Yang PC, Lee YT. Hypovolemic shock and mortality after ingestion of Tripterygium wilfordii hook F.: a case report. Int J Cardiol . 1995;49(2):173-177.

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