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Thunder God Vine

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

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.

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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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

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