What is Thunder God Vine

Thunder God Vine also known as the root of Tripterygium wilfordii Hook F, “Lei Gong Teng” or “Lei Kung Teng”, has long been used in traditional Chinese medicine to treat autoimmune and inflammatory conditions as well as cancer ¹. Thunder God Vine or Tripterygium wilfordii Hook F is a perennial Chinese herb commonly grown in southeast China, Japan, and Korea ². Tripterygium wilfordii Hook F has exhibited multiple pharmacological activities, such as anti-inflammatory, immune modulation, anticancer, and antifertility activities ³.

In China the Thunder God Vine plant (Tripterygium wilfordii Hook F), known as lei kung teng or lei gong teng, has a long history of use in traditional Chinese Medicine for treating swelling, fever, chills, sores, joint pain, and inflammation ⁴. Preparations of Tripterygium wilfordii Hook F began to be used in allopathic medicine in China in the 1960s to treat rheumatoid arthritis and inflammation ⁵. Since then Thunder God Vine has also been used for cancer, chronic nephritis, hepatitis, systemic lupus erythematosus, ankylosing spondylitis, and a variety of skin conditions ⁶. Biochemical analysis has shown that Tripterygium wilfordii Hook F contains a vast array of natural products with strong biological activities, which may explain its multiple uses in traditional and allopathic medicine in China. Most clinical studies used the chloroform–methanol extract of Thunder God Vine root extract in which the content of triptolide is defined as 33 µg triptolide per 20 mg tablet.

Of the approximately 380 metabolites isolated from the Thunder God Vine or Tripterygium wilfordii Hook F plant, 95% are terpenoids ⁷. Three diterpenoids— triptolide, tripdiolide, and triptonide ⁷ are the most abundant and account for the immunosuppressive and anti-inflammatory effects observed with the root extracts in both in vitro (test tube) and in vivo (animal) studies ⁸. Triptolide and celastrol (also known as tripterine) are two main active compounds isolated from Thunder God Vine with the potent anticancer activity ⁹. Numerous studies have reported that both triptolide and celastrol (tripterine) have the anticancer effects by inducing cell cycle arrest and apoptosis in various cancer cells in vitro and in vivo ¹⁰, ¹¹. Mechanistically, triptolide directly binds to the subunit of transcription factor 2 (TFIIH), excision repair cross-complementation group 3 (ERCC3, also known as XPB), and inhibits its DNA-dependent ATPase activity, which leads to the inhibition of RNA polymerase II–mediated transcription and likely nucleotide excision repair ¹². Celastrol has been identified as a novel inhibitor of HSP90 and displays anticancer activity by inducing the degradation of HSP90 client proteins, such as AKT, EGFR, CDKs, IAPs and p53, etc ¹³. The identification of XPB and HSP90 as the target of triptolide and celastrol respectively accounts for the majority of their known biological activities ⁹.

Currently, Thunder God Vine is promoted for use orally (by mouth) for rheumatoid arthritis, multiple sclerosis, Crohn’s disease, lupus, psoriasis, fever, and other conditions. It is also promoted for use topically (applied to the skin) for rheumatoid arthritis. A small amount of preliminary research suggests that thunder god vine might be helpful for Crohn’s disease ¹⁴, some kidney disorders ¹⁵, ¹⁶ and psoriasis ¹⁷, but there are no definite conclusions. There is not enough evidence to show whether thunder god vine is helpful for other health conditions.

Thunder God Vine can be extremely poisonous if the extract is not prepared properly. Thunder God Vine should not be used during pregnancy because it may cause birth defects. Abnormal development of mouse embryos has been observed in vitro (test tube study) ¹⁸ and human occipital meningoencephalocele of a newborn associated with use of the extract by the mother has been reported ¹⁹. Little is known about whether it’s safe to use thunder god vine while breastfeeding.

Several Tripterygium wilfordii Hook F preparations derived from Thunder God Vine extracts are available, including Thunder God Vine tablets and Tripterygium wilfordii glycosides tablets. However, the clinical application of Tripterygium wilfordii Hook F is limited by its narrow therapeutic window and potentially severe toxicity toward several organs including liver and kidney ²⁰.

The most frequent side effects of Thunder God Vine are gastrointestinal tract disturbances especially diarrhea, abnormal heart rates, high blood pressure, less red blood cell production, leukopenia (decreases in white blood cells), thrombocytopenia (low platelet count), skin rashes, skin hyperpigmentation, kidney problems, decreased bone mineral content (with long-term use), infertility, menstrual disorders in females (such as dysmenorrhea and irregular menstruation), headache, and hair loss ²¹. An adverse effect on renal function such as a decrease in creatinine clearance in elderly patients has also been documented. Treatment-related death has rarely been seen and has occurred mostly in patients who either received an overdose due to self-prepared decoctions or alcoholic extracts of Tripterygium wilfordii Hook F (tincture) ¹⁷. Causes of death were myocardial damage, renal failure, low volume shock or severe intestinal tract disturbances ²². The side effect-related withdrawal rate for the chloroform–methanol extract of Tripterygium wilfordii Hook F in a 3-month trial was only 2.9% ²³. Because some of these side effects are serious, the risks of using thunder god vine may be greater than its benefits.

Thunder God Vine benefits

During the past three decades, more than a thousand patients with different autoimmune and inflammatory diseases have been treated with Thunder God Vine root extracts in China in clinical trials and practice ²⁴. It has been reported that rheumatoid arthritis ²⁵, systemic lupus erythematosus (SLE) ²⁶, systemic scleroderma ²⁷, ankylosing spondylitis ²⁸, psoriatic arthritis ²⁹, Behçet’s disease ³⁰, polymyositis ³¹, Henoch-Schonlein purpura ³², reactive status of leprosy ³³, chronic lymphocytic thyroiditis ³⁴, chronic nephrotic syndrome ³⁵, IgA nephropathy ³⁶ as well as adult and childhood nephritis ³⁷ were treated successfully ³⁸. Triptolide was also used for prevention of graft rejection after kidney transplantation ³⁹. Furthermore, triptolide was effective in the treatment of a variety of skin diseases such as psoriasis ²⁹, allergic contact dermatitis, polymorphous light eruption, erythema multiforme, atopic dermatitis and pemphigus ⁴⁰. Randomized, double-blind, placebo controlled clinical trials in the US have confirmed the efficacy in the treatment of rheumatoid arthritis ⁴¹, ⁴².

It has reported that triptolide could sensitize cancer cell lines to several chemotherapeutic drugs in vitro (test tube) and in vivo (animal) studies, including cisplatin, adriamycin, temozolomide and sorafenib, etc ⁴³, ⁴⁴. Celastrol (tripterine) in combination with chemotherapeutic agents also show the synergistic anticancer effect on suppressing the proliferation of multiple type of cancers such as melanoma, hepatocellular carcinoma, breast cancer and lung cancer ⁴⁵. Although triptolide and celastrol coexist in Thunder God Vine and have the different anticancer molecular mechanisms, the anticancer effect of triptolide in combination with celastrol is still unknown.

Preliminary research suggests that oral or topical Thunder God Vine (Tripterygium wilfordii Hook F) might be beneficial for rheumatoid arthritis signs (erythrocyte sedimentation rate [ESR], rheumatoid factor [RF], C-reactive protein [CRP], grip strength and 15m walking time) and symptoms compared to certain drugs or placebos ⁴⁶. Specifically regarding its use for rheumatoid arthritis, numerous preclinical studies have demonstrated immune-suppressive, cartilage protective, and anti-inflammatory effects ²¹. Some studies have suggested that Thunder God Vine plus standard medical treatment may be more effective than standard treatment alone for symptoms such as joint swelling and tenderness. Other studies have suggested that Thunder God Vine on its own may be at least as effective as standard medical treatments in reducing joint swelling and tenderness.

Uncontrolled trials from 1980s enrolling more than 100 rheumatoid arthritis patients have shown 87% response rates. To evaluate these claims, in 2002 ⁴², a study recruited 35 patients and randomized them to placebo, low (180 mg/day) or high (360 mg/day) dose of an ethanol/ethyl acetate extract of Thunder God Vine. After 5 months, 80% of the high-dose and 40% of the low-dose groups had achieved an American College of Rheumatology 20% (ACR20) improvement response criteria, compared with none of the patients taking placebo ⁴². Both physical function and inflammation were improved. Diarrhea was the most common adverse event followed by nausea. A systematic review of a total of seven randomized controlled trials was done in 2009 by Jiang and colleagues ⁴⁷ to evaluate the efficacy and safety of Thunder God Vine in the treatment of rheumatoid arthritis. An interesting conclusion was that although Thunder God Vine was clinically as effective as disease-modifying anti-rheumatic drugs (DMARDs), no effect was observed in delaying bone erosions. However, these are small sample size trials and in six of them there were some methodological limitations that can have produced relevant biases. Subsequently, Goldbach-Mansky’s group enrolled 121 rheumatoid arthritis patients and randomly assigned them to receive Thunder God Vine extract (60 mg, three times daily) or sulfasalazine ⁴⁸. After 6 months, 68% of those treated with Thunder God Vine and only 36% of those under sulfasalazine reached an ACR20 response. More patients in the sulfasalazine group experienced moderate or severe adverse effects. The most frequent side effects in patients receiving Thunder God Vine were diarrhea, nausea, dyspepsia, abdominal pain, and upper respiratory tract infection ⁴⁸. In 2012, an interesting concept was tested in a randomized controlled, single-blind clinical trial that used external application of Thunder God Vine extracts in 67 active rheumatoid arthritis patients with positive results and only referring two cases of mild skin allergy ⁴⁹. This result has been also reported by Cibere et al. ⁵⁰. In 2013, due to inconsistency in some clinical trial data, Liu et al. ⁵¹ performed a meta-analysis of randomized controlled trials. In this review, authors have concluded that Thunder God Vine extracts are a sort of “herbal DMARD” with a similar efficacy to synthetic DMARDs in rheumatoid arthritis treatment and that well-designed confirmatory randomized controlled trials should be done ⁵¹. Recently, Zhang and co-workers ⁵² have shown in a multicenter, open-label, randomized controlled trial that combined therapy of methotrexate and Thunder God Vine was more effective than methotrexate monotherapy in the treatment of active rheumatoid arthritis patients ⁵³. In this study, about 52.7% of the 207 patients experienced adverse events, which were seen in 46.4, 62.3, and 49.3% of patients receiving Thunder God Vine (20 mg, three times per day), methotrexate (12.5 mg/week), and Thunder God Vine + methotrexate, respectively ⁵². The most common adverse event was mild gastrointestinal side effect, reported by 43.5% of patients on methotrexate and by 34.8% of those receiving the combination ⁵². According with this reported experience, combining both medications might be a good strategy to decrease the amount of methotrexate needed, which may reduce the toxic effects that can limit methotrexate long-term treatment ⁵⁴. This report is in accordance with an observation from 2001 ⁵⁵, where 70 rheumatoid arthritis patients receiving methotrexate combined with small doses of Thunder God Vine polyglycoside (10 mg, three times a day) had a better effect and less adverse reactions than monotherapy with methotrexate. Finally, an interesting clinical trial has been conducted in order to evaluate the efficacy and safety of etanercept plus Thunder God Vine (10 mg, three times per day) in elderly patients with active rheumatoid arthritis. Etanercept plus Thunder God Vine had an equivalent therapeutic effect to that of Etanercept plus methotrexate and were both well tolerated ⁵⁶. Altogether, these clinical trials show relevant data regarding the use of Thunder God Vine in rheumatoid arthritis treatment; however, there are limitations in their design, including the open-label design, short duration (6 months), and lack of radiological assessment. Although Thunder God Vine extracts showed efficacy in the symptomatic treatment of rheumatoid arthritis patients, it is still unclear if it provides structural damage control.

More recently, different extracts of Tripterygium wilfordii Hook F have been used in Chinese allopathic medicine for the treatment of autoimmune and inflammatory diseases, and small controlled trials reported good responses with Tripterygium wilfordii Hook F extracts in patients with cadaveric kidney transplants ⁵⁷ and Crohn’s disease ⁵⁸.

Regarding the clinical experience with thunder god vine in cancer, two water-soluble derivatives of triptolide (thunder god vine diterpenoid, a different class from celastrol) have been synthesized (PG490-88 and F60008) and approved for entry into a Phase I clinical trial for the treatment of solid tumors. PG490-88 will be tested in a Phase I clinical trial for prostate cancer in USA ⁵⁹. Also, a phase I trial was performed with F60008 given intravenously in 20 advanced solid tumors patients in a total of 35 cycles. The most frequent side effects were mild anemia, fatigue, nausea, vomiting, diarrhea, and constipation. Two lethal events were observed and the high inter-individual variability rendered this derivative far from optimal ⁶⁰.

In the case of neurodegenerative disorders, no clinical data are available about the use of thunder god vine. A study regarding the use of celastrol in amyotrophic lateral sclerosis (ALS) concludes that further preclinical data, human toxicity, and pharmacokinetic results are required to proceed with trials ⁶¹.

The therapeutic effect of thunder god vine extracts has also been evaluated in diabetic patients. A prospective clinical trial enrolled 45 patients with type 2 diabetic kidney disease, randomly divided into three groups: thunder god vine (1–2 mg/kg/day), irbesartan (150–300 mg/day), and thunder god vine combined with irbesartan ⁶². Data have shown that treatment with thunder god vine for 12 weeks may be effective in preventing podocyte injury with a synergistic protective effect with irbesartan ⁶². Another clinical trial has been performed to evaluate the efficacy of thunder god vine in the treatment of type 2 diabetes mellitus-induced nephropathy ⁶³. A total of 65 patients were enrolled in this 6-month, prospective, controlled study, and randomized into treatment groups: 120 mg/day of thunder god vine extract for 3 months, followed by 60 mg/day for 3 more months, or 160 mg/day of valsartan for 6 months ⁶³. It was found that thunder god vine can significantly reduce the urine protein levels ⁶³. Similar nephroprotective effects for thunder god vine preparations have been described in a meta-analysis of randomized controlled trials of chronic kidney disease patients ¹⁵.

A clinical trial in China also tested the use of thunder god vine in human kidney transplantation ⁵⁷. Rejection occurred in 4.1% of patients treated with thunder god vine versus 24.5% of control patients, showing efficacy in the prevention of renal allograph rejection. All patients tolerated well thunder god vine administration during the 5 years of the study ⁵⁷. This interesting potential of thunder god vine, which was already demonstrated in different in vitro and in vivo experimental set-ups, may be of interest in several medical areas.

Thunder God Vine rheumatoid arthritis

Rheumatoid arthritis is a chronic inflammatory disorder that can affect more than just your joints. In some people, the condition can damage a wide variety of body systems, including the skin, eyes, lungs, heart and blood vessels. Rheumatoid arthritis occurs when your immune system mistakenly attacks your own body’s tissues. More women than men get rheumatoid arthritis. It often starts in middle age and is most common in older people. You might have the disease for only a short time, or symptoms might come and go. The severe form can last a lifetime.

Several advantages related to Thunder God Vine (Tripterygium wilfordii Hook F) have been previously reported, including properties of decreasing ESR, RF, C-Reactive Protein (CRP), and risk of adverse events related to rheumatoid arthritis ⁴⁶. Tripterygium wilfordii Hook F. (20 mg three times a day) has also been investigated in the context of efficacy and safety in a clinical trial (24 weeks) involving 207 patients with active rheumatoid arthritis and compared with methotrexate (12.5 mg once a week) treatment as well as a combined treatment ⁵². This study underlines a series of positive outcomes of efficiency (similar ones were also reported in the animal model) such as the American College of Rheumatology 20/50/70 (ACR20, ACR50, ACR70) response, remission rate and low disease activity rate as well as significant improvements in the health assessment questionnaire and 36-item short-form health survey questionnaire scores. However, side effects, namely the development of irregular menstruation, are also considered and reported for all treatment groups ⁵². In the 2-year follow-up of the “Comparison of Tripterygium wilfordii Hook F. with methotrexate in the Treatment of Active Rheumatoid Arthritis” (TRIFRA) study ⁵², which investigated Tripterygium wilfordii Hook F. compared or combined with methotrexate in controlling the manifestations in patients with DMARD-naive active rheumatoid arthritis, it is demonstrated that Tripterygium wilfordii Hook F. monotherapy was not inferior to methotrexate monotherapy in controlling disease activity and retarding radiological progression ⁶⁴. It is worth noting that treatment with Tripterygium wilfordii Hook F. in the setting of rheumatoid arthritis has also been investigated further in the context of identifying the predictors to its response in a two-stage trial involving overall more than 300 patients with active rheumatoid arthritis. In this study ⁶⁵, Tripterygium wilfordii Hook F. therapy was compared to methotrexate and sulfasalazine combination therapy in a setting of patients classified into predictor positive and predictor negative groups. Results of these efforts have led to the identification of five predictors (diuresis, excessive sweating, night sweats for positive; and yellow tongue-coating, a burning pain in the joints for negative groups), which further highlights that natural products can be both efficient and effective ⁶⁵.

Thunder God Vine Crohn’s disease

Thunder God Vine is generally used in the treatment of Crohn’s disease in China. Its therapeutic benefits have been explored in an open-label clinical trial conducted in 20 Crohn’s disease patients treated with Thunder God Vine tablets (120 mg daily) for a period of 12 weeks. Crohn’s disease Activity Index diminished during the first 8 weeks, and the endoscopic improvement was observed after 12 weeks. Inflammatory parameters, including C-reactive protein (CRP), also decreased ⁵⁸. In addition, two placebo-controlled trials and one prospective single-blind clinical trial have studied the therapeutic potential of polyglycoside Thunder God Vine (1 mg/kg daily) in the prevention of postsurgical relapses in patients with Crohn’s disease. Results from these studies suggest that this is an effective and well-tolerated drug ⁶⁶, ⁶⁷, ¹⁴. Recently, a randomized clinical trial has shown that Thunder God Vine (1.5 mg/kg/day) was comparable to azathioprine to prevent postoperative clinical recurrence of Crohn’s disease, although less efficient in preserving endoscopic remission at week 52 ⁶⁸. An additional clinical trial enrolled 198 patients with Crohn’s disease, which were randomized to receive mesalazine (also called mesalamine or 5-aminosalicylic acid) (3 g/day), low-dose Thunder God Vine (1.5 mg/kg/day) or high-dose Thunder God Vine (2.0 mg/kg/day) over a 52-week period ⁶⁹. Importantly, data have shown that less patients in the high-dose group (7/71) had clinical recurrence in comparison with patients in the low-dose (15/68) or patients treated with mesalazin (17/59). However, patients under mesalazine (mesalamine or 5-aminosalicylic acid) treatment had less adverse effects than those treated with high-dose and low-dose of Thunder God Vine ⁶⁹.

Thunder God Vine psoriasis

Psoriasis is a chronic, recurrent, inflammatory skin disorder characterized by clearly defined, red and scaly plaques affecting approximately 2% of the world’s population. Psoriasis causes itchy or sore patches of thick, red skin with silvery scales. You usually get the patches on your elbows, knees, scalp, back, face, palms and feet, but they can show up on other parts of your body. Psoriasis is classified into several subtypes. Psoriasis vulgaris is the most common type of psoriasis, which manifests as well-demarcated, scaly patches on the skin. Psoriasis is considered severe if more than 10% of a patient’s body surface is affected or if a patient scores more than 10 on the Psoriasis Area Severity Index (PASI) ⁷⁰.The therapy for psoriasis vulgaris varies depending on the severity and extent of skin involvement. Topical therapies are used for mild or localized disease while systemic therapies and phototherapy are used for patients with moderate to severe disease.

A randomized clinical trial has shown equal efficacy of Thunder God Vine (20 mg, three times a day) with acitretin (58 Thunder God Vine; 57 acitretin) in moderate to severe psoriasis vulgaris found no significant difference in median Psoriasis Area Severity Index (PASI) score improvement between two groups at 2, 4, and 8 weeks ¹⁷. 115 patients were randomly assigned in a 1:1 ratio to receive either a chloroform–methanol extract of Tripterygium wilfordii Hook F 20 mg 3 times a day plus a placebo matching acitretin 30 mg once a day or acitretin 30 mg once a day plus a placebo matching a chloroform–methanol extract of Tripterygium wilfordii Hook F 20 mg three times daily, both for 8 weeks. There was also no significant difference in PASI 25, PASI 50, PASI 75, and PASI 90 response between the two groups at 2, 4, and 8 weeks. There was a significant increase in the level of aspartate transaminase and triglycerides in the Tripterygium wilfordii Hook F group ¹⁷. In the acitretin group, there was a significant increase in the level of alanine transaminase, cholesterol, and HDL (high-density lipoprotein) ¹⁷.

In another clinical trial a Thunder God Vine extract was used in comparison with placebo in a randomized, double-blind trial in 61 patients with plaque psoriasis ⁷¹. Patients received 18 g per day of a Tripterygium wilfordii Hook F ethanol extract for 4 weeks. The psoriasis area and severity index (PASI) decreased from initially 9.1 to 4.2 in comparison with the placebo group in which the PASI remained almost stable after 2 weeks of treatment. In three patients the skin was completely cleared. Analysis after 4 weeks of treatment showed a further decrease of PASI to 2.1 with almost no change in the placebo group ⁷¹. In 64% of the patients a PASI 100 could be observed. Two patients in the treatment arm discontinued the study due to severe gastrointestinal reactions and four patients developed moderate gastrointestinal reactions which could be treated with metoclopramide. One woman had a delayed menstrual cycle which normalized after treatment was stopped.

Another double-blind, randomized clinical study involved 100 patients with psoriasis vulgaris ⁷². Fifty patients received Thunder God Vine ethanolic extract (18 g daily orally), another 50 patients were treated with an equal dose of an extract of indigo naturalis (a dark blue plant used to treat psoriasis in traditional Chinese medicine). PASI decreased significantly from 9.4 to 4.3 (indigo naturalis: from 11.0 to 9.5) after 2 weeks of treatment ⁷². In 12 patients the skin was completely cleared. Analysis after 4 weeks of treatment showed further significant improvement of PASI to 2.2 in the treatment group whereas the PASI in the placebo group remained almost stable. In 64% of patients receiving the Tripterygium wilfordii Hook F extract but only in 28% of the indigo group a PASI 100 was observed ⁷². Gastrointestinal reactions were seen in two patients who could be treated symptomatically.

Two studies used a combination of triptolide with macrolide antibiotics such as azithromycin and erythromycin. In a quasi-randomized, open-label study 131 patients with guttate or plaque psoriasis participated ⁷³. In the first treatment group patients received 20 mg chloroform–methanol thunder god vine root extract orally three times daily for 4 weeks followed by 2 weeks of i.v. administration of azithromycin (500 mg/day). The second treatment group received chloroform–methanol thunder god vine root extract only and patients in the control groups received azithromycin. A reduction of the PASI of more than 60% was seen in 88.9% of patients in the first treatment group and in 40.0% of patients psoriasis was totally cleared. Patients treated with chloroform–methanol thunder god vine root extract only showed a 60% reduction of PASI in 67.4% of patients in comparison with 41.9% of patients treated with azithromycin. The most common adverse event under chloroform–methanol thunder god vine root extract treatment was nausea. In four cases irregular menstruation developed and in two cases leukocytopenia was observed. All these side effects were reversible within 2 weeks after treatment had been stopped.

In a further randomized trial 54 psoriasis patients were treated with chloroform–methanol thunder god vine root extract (20 mg, three times daily orally) combined with erythromycin (0.25 g four times daily) and glycyrrhizin (150 mg three times daily) ⁷⁴. In this study 74.1% of patients in the treatment group showed a reduction of PASI of 60% compared with 50% in the control group after 6 weeks of treatment. The short term and long term (over 1 year) recurrence rate in both groups showed no significant difference. Adverse reactions included slight dizziness (one case), menoxenia (one case) and elevated aminotransferases (one case). Adverse events were reversible 2 weeks after treatment was stopped ⁷⁴.

Plaque psoriasis, pustular or erythrodermic psoriasis or psoriatic arthritis were included in a randomized trial in 98 patients ⁷⁵. Patients were randomized to receive chloroform–methanol thunder god vine root extract (20 mg three times daily), bimolane (0.2 g twice a day) and folic acid (5 mg twice a day) in the treatment group or only bimolane and folic acid in the control group. Bimolane is a member of a bis (2,6-dioxopiperazine) class of drugs and has been widely used in China as an anti-neoplastic agent and for the treatment of psoriasis. Folic acid is given to patients to reduce the likelihood of oral ulcers and blood count abnormalities similar to the use with methotrexate. After 8 weeks 92.9% of patients in the treatment group showed a PASI 75 response compared with 71.2% in the control group. Total skin clearance occurred in 50% and 31.8% of the patients, respectively. Two patients in the treatment group in comparison with five patients in the control group relapsed 4 weeks after discontinuing treatment.

Another medication named Di Yin Pian, or Ampepitidium et Elementum, is also widely used to treat psoriasis in China. This was used as a comparator in four clinical trials with triptolide. One randomized trial involved 158 patients with plaque psoriasis, pustular or erythrodermic psoriasis and psoriatic arthritis ⁷⁶. Patients were randomized into three groups receiving chloroform–methanol thunder god vine root extract (20 mg three times daily orally), or Ampepitidium et Elementum (3 g twice daily orally), or a combination of chloroform–methanol thunder god vine root extract and Ampepitidium et Elementum ⁷⁶. A reduction in PASI of 70% was achieved by 78.4% of the patients receiving chloroform–methanol thunder god vine root extract, similar to the patients receiving Ampepitidium et Elementum (79.4%). A significant improvement of 95.4% reaching a PASI70 was seen in the combination group ⁷⁶. In the chloroform–methanol thunder god vine root extract group only 8.1% of the patients showed gastrointestinal adverse events, much less than in the other groups (85%).

Another randomized study included 58 patients with plaque psoriasis and was carried out over 8 weeks ⁷⁷. Participants in the treatment group received chloroform–methanol thunder god vine root extract (10 mg orally four times daily) and Ampepitidium et Elementum (1.8 g orally twice a day). In the control group Ampepitidium et Elementum was administered (3 g twice a day). Improvement in PASI (from 9.3 ± 4.1 to 4.3 ± 1.1) occurred after 4 weeks with chloroform–methanol thunder god vine root extract therapy. In the control group the PASI dropped from 10.3 ± 4.5 to 7.5 ± 1.3. After 8 weeks PASI 70 was seen in 89.3% of the patients in the treatment group compared with only 40% in the control group ⁷⁷. Only one patient in the treatment group developed menoxenia and two patients developed GI reactions. Side effects were reversible.

Another clinical trial in 2004 included 89 patients with plaque psoriasis ⁷⁸. Participants were randomly assigned to receive chloroform–methanol thunder god vine root extract (20 mg three times daily orally) and Ampepitidium et Elementum (3 g twice daily orally) as the treatment group, or the same dose of Ampepitidium et Elementum as the control group. Total skin clearance occurred in 48.2% of the patients in the treatment group after 10 weeks, which was significantly higher when compared with 18.2% of the patients in the control group ⁷⁸.

The same treatment as mentioned above was used in a study including 95 patients with plaque psoriasis ⁷⁹. After 9 weeks of treatment 71.2% of the patients in the treatment group showed a reduction of PASI of 60% as compared with 46.5% in the control group ⁷⁹. Three patients in the treatment group developed gastrointestinal reactions at day 8, two patients developed leukocytopenia (≤4.0 × 10⁹/l) and in one patient elevated alanine transaminases occured. In all patients adverse effects were reversible after reducing the dose of chloroform–methanol thunder god vine root extract.

In a further study a decoction prepared from roots of Tripterygium wilfordii Hook F was used in a randomized study involving 208 patients with plaque psoriasis ⁸⁰. One hundred and two patients received 50 ml of the decoction per day as oral treatment together with halcinonide ointment for external use once a day. As a control group 96 patients received only halcinonide ointment once a day. The study ended after 4 weeks. In 86.6% of the treatment group a reduction of PASI of 60% was observed and 45.5% of the patients achieved a PASI100. In comparison, 39.6% of the patients in the control group showed a reduction of PASI of 60%. Adverse reactions included tolerable gastrointestinal reaction (11 cases), delayed menstrual period (three cases), and mild leukocytopenia (one case) ⁸⁰.

The design of numerous of the studies which have been published and discussed may not meet state-of-the-art criteria for clinical trials today. Proper definition of the selected population such as moderate-to-severe psoriasis and the inclusion only of plaque psoriasis following standard definitions were not performed. In addition, significant improvement of PASI in patients with only mild forms of psoriasis may bias a favourable efficacy outcome. Another drawback for a better understanding of the benefit–risk profile of triptolide is the lack of long term trials or even reports of open studies running for more than 1 year. On the background of published data to date it is difficult to judge the full potential of Thunder God Vine (Tripterygium wilfordii Hook F) for use in psoriasis.

Thunder God Vine root weight loss

In obese condition, hyperleptinemia coexists with the loss of response to leptin, an inhibitor of food intake and inducer of energy expenditure. This phenomenon has been defined as leptin resistance and the restoration of its sensitivity is a useful strategy to treat obesity. Recently, in a hyperleptinemic diet-induced obese mice, celastrol (also known as tripterine) has shown the ability to increase leptin sensitivity ⁸¹. It can restore the leptin signaling in neurons by overexpressing anorexigenic peptides pro-opiomelanocortin (POMC) and/or repressing orexigenic peptides [neuropeptide Y (NPY)/AgRP] ⁸². Also, celastrol ability to increase mitochondrial function and HSF-1, a regulator of energy expenditure, through the activation of a PGC1α-dependent metabolic program in adipose tissues and muscles leads to an augment in energy expenditure and represents a possible therapeutic strategy to treat obesity and its metabolic consequences ⁸³.

Thunder God Vine side effects

Thunder god vine can be extremely poisonous if the extract is not prepared properly. Thunder god vine should not be used during pregnancy because it may cause birth defects. Little is known about whether it’s safe to use thunder god vine while breastfeeding.

The most frequent side effects of Thunder God Vine are gastrointestinal complaints especially diarrhea, abnormal heart rates, high blood pressure, less red blood cell production, leukopenia (decreases in white blood cells), thrombocytopenia (low platelet count), skin rashes, skin hyperpigmentation, kidney problems, decreased bone mineral content (with long-term use), infertility, menstrual disorders in females (such as dysmenorrhea and irregular menstruation), headache, and hair loss ²¹. An adverse effect on renal function such as a decrease in creatinine clearance in elderly patients has also been documented. Treatment-related death has rarely been seen and has occurred mostly in patients who either received an overdose due to self-prepared decoctions or alcoholic extracts of Tripterygium wilfordii Hook F (tincture) ¹⁷. Causes of death were myocardial damage, renal failure, low volume shock or severe intestinal tract disturbances ²². The side effect-related withdrawal rate for the chloroform–methanol extract of Tripterygium wilfordii Hook F in a 3-month trial was only 2.9% ²³. Because some of these side effects are serious, the risks of using thunder god vine may be greater than its benefits.

Treatment with triptolide is often associated with dysmenorrhea (period or menstrual cramps) and irregular menstruation ⁸⁴. Administration of triptolide (40 mg daily for 1 month) can cause reversible sterility in men, with a 50% reduction of sperm motility. The long term administration (over 2 months) of triptolide or an extract of Tripterygium wilfordii Hook F can lead to severe reduction of both sperm counts and motility. This effect was first noted in the treatment of Chinese men with Tripterygium wilfordii Hook F extracts with a daily dose of 20 mg to 30 mg to treat rheumatoid arthritis and psoriasis who became sterile within 2 months. In these patients testosterone and luteinizing hormone (LH) concentrations as well as libido and sexual potency were unchanged ⁸⁵. This effect led to the investigation of triptolide as a contraceptive for men ⁸⁶. However, as infertility was not reversible in rats the interest in triptolide has dropped for this application ⁸⁷.

An adverse effect on renal function such as a decrease of creatinine clearance in elderly patients is documented ⁸⁸. There is at least one report in which induction of hypertension by triptolide has been described ⁸⁹.

There is one case report about a young man who developed profuse vomiting, diarrhea, leukopenia, renal failure, profound hypotension and shock after oral administration of the extract ⁹⁰. Therapeutic concentrations showed a hematotoxic effect leading to bone marrow suppression ⁹¹.

Abnormal development of mouse embryos has been observed in vitro ¹⁸ and human occipital meningoencephalocele of a newborn associated with use of the extract by the mother has been reported ¹⁹.

Up to 6% of patients treated with Tripterygium wilfordii Hook F extracts developed leukopenia. The immunosuppressive effects of Tripterygium wilfordii Hook F may also render patients susceptible to infectious diseases like upper respiratory tract infections ⁹². Most adverse events were reversible either spontaneously or after dose adjustment. Interestingly, the side effect-related withdrawal rate for chloroform methanol Tripterygium wilfordii Hook F extract in a 3 month trial was only 2.9% ⁹³.

Thunder God Vine summary

In summary, clinical trials have only tested thunder god vine or Tripterygium wilfordii Hook F extracts. Despite its potential clinical usefulness, the sale of thunder god vine has been prohibited in many countries because the misuse of the herb can cause severe consequences, including diarrhea, nausea, and infertility. Even an apparent non-toxic dose may cause antifertility effects in men, male rats, and guinea pigs due to oral administration of some toxic components of thunder god vine extracts. Unfortunately, in men, this dose is only one-third of the recommended dose for the treatment of rheumatoid arthritis or skin diseases ⁹⁴. As such, treating patients with thunder god vine bioactive compounds with known pharmacological properties may circumvent toxicological limitations.

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