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Lei Gong Teng (tripterygium wilfordii) Tablets

Introduction: Lei Gong Teng (tripterygium wilfordii) tablet is a natural herbal product commonly used in Traditional Chinese Medicine. This herbal remedy has powerful medicinal actions, and it is strongly recommended consulting a licensed health care provider with knowledge of herbal medicine, before using any herbal product. Triptolide and other compounds in Lei gong teng are still in the experimental or trail stage in the West, and Triptolide or Lei gong teng extract tablets are not officially approved antitumor medications. However, in China and other Asian countries, Lei gong teng is a commonly prescribed medication for rheumatoid, inflammatory conditions, and sometimes as an adjunctive cancer therapy along TCM or conventional cancer care. Lei gong teng interferes with the reproduction of tumor cells and induces cancer cells apoptosis, but Lei gong teng can also lower the function of the immune system. Therefore, when administered for anti-tumor therapy, Lei gong teng should be used along some forms of immune support, such as astragalus injections or astragalus 5:1 concentrated extract for oral administration.

Chemical composition: Wilfordine; Wilforgine; Wilfordine; Wilforine; Wilfotrine; Wilforzine; Triptolide; Tipdiolide; Tripteroilide; (+)-medioresinol; (-)syringaresinol; Nubiletin; Tripdiolide; Triptolidenol; Hypolide; Triptonide; 16-hydroxytriptolide; Tripchlorlide; Triptriolide; Tripdiotolnide; Wilforlide A, B; 3-epikatonic acid; Cangoronine; Regelin; Salaspermic acid; Euonymine; Wilfordsine; b-sitosterol; Dulcitol; Evonymine; Polysaccarides; 1-epicatechin; Triptotriterpenonic acid A; Triptotriterpenoidal lactone A; Oleanane-9,12-dialkene-3-ketone; 16-hydroxy-19, 2O-epoxy-kaurane; 13, 14-epoxide 9, 11, 12-trihydroxytriptolide; 3-hydroxy-2-oxo-3-fridelen-20a-carboxylic acid; 3b-hydroxy-D:B-friedoolean-5:6-epoxy-29-oic acid; Triptofordins A, B, C-1, C-2, D-1, D-2, E, F-1, F-2, F-3, F-4.

According to TCM medical terms: Lei Gong Teng is mainly used for eliminating dampness by dispelling pathogenic wind, alleviating pain by reducing swelling, promoting circulation by activating the meridians and collaterals, and cleansing toxins by expelling pathogenic heat. Lei Gong Teng is primarily used by patients with arthralgia due to pathogenic wind, cold and dampness (those words refer to medical conditions and do not have the same "climate related" literal meanings. It is necessary to have some basic knowledge of TCM, in order to understand the medical meanings of those terms). 

Description: usually in bottles of 100 tbs containing 10mg of polyglycoside per tablet. 

Dosage: taken orally, 1-1.5mg per 1kg of body weight (the largest dosage per day should not exceed 90mg). the dose is usually divided and taken b.i.d. Two to three months constitute one course of treatment.

Precaution 

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Contraindication: Pregnancy.

Toxicity: Acute toxicity test on rats show that Lei Gong Teng cortex can induce significant pathologic change to cardiac muscles, forming multiple tiny myolysis focuses, causing renal tuber cell degeneration and necrosis, and lymphocyte disintegration. In rats, the organs most sensitive to the toxicity of Lei Gong Teng total saponins are those of the gastrointestinal system, the hematopoietic system, and the germinal epithelium of testis. Either prolonged use or overdose of Lei Gong Teng inhibits white blood cells and blood platelets in dogs, and can cause damages to the germinal epithelium of dogs, rats, and mice, inhibiting spermatogonium division and resulting in a decrease in, or complete disappearance of, various germ cells. (1)

Health conditions: Exercise caution when administering to patients with heart, liver, or kidney problems, or with a low white blood cell count.

Side effects: There have been reports of one case of Lei Gong Teng overdose, and one case of poisoning resulting in acute renal failure. (2, 3)

Inter-action: There is some information on possible drug interactions between Lei Gong Teng and Ceftazidime Injection and Dextrose Injection.

Pharmacology

Effects on the reproductive system: An analysis of semen specimens taken from subjects before and after treatment with this formula finds that the treatment introduces macrophages and causes microencapsulation of sperm cells. (4) Furthermore, experiments show that when administered to rats, Lei Gong Teng monomers T4, T7, T15, and T10 can lower the levels of total alkaline protein and sperm nucleus protein in the subject's semen. (5) Also, both total glycosides of tripterygimum wilfordii (GTW) and T4 can cause morphologic changes to male rat's anterior pituitary LH cells, resulting in castration-like changes in LH cells. (6)

Effects arthritis: Administered to rats of collagen-induced arthritis at 15 and 30mg/kg, tripterine, an active component of Lei Gong Teng, can alleviate foot swelling and inhibit the production of interleukin-1 and interleukin-2. (7) Lei Gong Teng film can significantly decrease rat's inflammatory rat tissue's capillary permeability, decrease the content of prostaglandin E2 (PGE2) in inflammatory tissues, and significantly alleviate pain. (8) Lei Gong Teng polyglycosides (TWP) can lower the levels of IL-1 and IL-6 in rats of adjuvant-induced arthritis, significantly inhibiting the proliferation of spleen cells. (9)

Effects on immunity: TWP has an inhibitory effect on the activation of T cells, the production of IL-2, the expression of IL-2 receptors, and activated T cell's reaction to IL-1. (10) Wilformine, an active component of Lei Gong Teng, can inhibit the autonomous proliferation of peripheral blood mononuclear cells in SLE cases and the function of B cells. (11) Through interfering with the DNA synthesis of lymphocytes, T10 can inhibit the immunologic function of lymphocytes and cause structural damages. (12)

Suppressing graft rejection: Experiments show that T4 can prolong the survival time of mice with a transplanted heart, and lessen the rate of the grafted organ being rejected. (13) Prior to grafting, immersing the skin in 15% Lei Gong Teng decoction at 37C (98.6K) for one hour can significantly delay the occurrence of graft rejection (P<0.01). (14)

Anti-inflammatory effects: At either 400 or 200 mg/kg, a water-based extract of Lei Gong Teng leaves has a significant inhibitory effect on carrageenin-induced swelling in rats, on dimethylbenzene-induced auricular infection and acetic acid-induced body twisting in mice, indicating that Lei Gong Teng has significant anti-inflammatory and analgesic effects. (15) Lei Gong Teng microcapsules (5-15mg/kg) are shown to have a dose-dependent inhibitory effect on canavaline-induced proliferation of spleen cells in mice. (16)

Antineoplastic effects: A new component that has an antineoplastic activity has been isolated from Lei Gong Teng extract. Administered by abdominal injections for 2-3 times, this new component of Lei Gong Teng can significantly prolong the survival time of mice of H22, S180, EAC and mammary cancer. Fed to mice of S37 and of 3-MCA-induced experimental lung cancer, it can inhibit the growth of the respective tumors by 42% and 65.13%. At 10 or 20 micrograms/ml, it can kill 95% of HL60 cells in 48 hours, and at 20 or 40 micrograms/ml, it can kill 90% of Daudi cells in 48 hours. At 5.10 micrograms/ml, it enhances the phagocytic function of isolated mouse peritoneal macrophage; at 20 micrograms/ml or above, however, its action reverts to inhibition. (17) 

Miscellaneous effects: Experiments show that Triptolide can inhibit the expression of IL-5 and GM-CSF in asthmatic guinea pigs, indicating that Lei Gong Teng has the potential for treating asthma-induced inflammation. (18)

Clinical Applications

Rheumatoid arthritis: Two groups of arthritis patients were treated with two kinds of pills containing different amounts of triptolide. Group A, of 36 patients, was treated with a pill containing 50mg of triptolide, two pills a time, three times a day; and Group B, of 32 patients, was treated with a pill containing 15mg of triptolide, beginning with one pill a time, three times a day, with the dose gradually increased to three pills a time, three times a day. The results (short-term): Group A: 2 cases resolved, 13 significantly improved, 16 improved, and 5 did not respond to the treatment, with a total effective rate of 86.1%. For Group B, the corresponding numbers were: 2, 7, 21, 2, and 93.8% respectively. (19)

Another study compared the effects of Lei Gong Teng and a Lei Gong Teng compund on the immunologic function of arthritis patients, and found that Lei Gong Teng had a relatively strong inhibitory effect on immunity, and could be an especially appropriate treatment for patients of acute rheumatoid arthritis with an elevated IgG and a dependence on hormones. (20)

Asthma:
One study treated 37 cases of infantile asthma with Lei Gong Teng Pian. A follow-up conducted eight months after the treatment found that the treatment had been effective on 33 patients, with a total effective rate of 89.18%. (21)

Another study treated 32 cases of severe bronchial asthma with Lei Gong Teng Pian (20mg a time, 3 times a day). After 5-35 days of treatment, 27 cases significantly improved and 5 improved. (22)

Renal illnesses: One study treated 15 cases of refractory infantile nephritis with Lei Gong Teng Pian (1.5mg/kg/day, administered in three takings). One unit of treatment consisted two 12-week periods, with the second 12-week period seeing only intermittent administrations of Lei Gong Teng Pian, but with another medication added: prednisone (2mg/kg/day, administered in three takings). The results: 8 cases resolved, 5 entered remission, and 2 entered partial remission. (23)

Another study treated 60 cases of nephritis with Lei Gong Teng Pian (60mg/day, administered in three takings). One unit of treatment consisted two 3-month periods. After the first three months, the patients rested two weeks and then continued the medication as follows: if they did not respond to the first three months' treatment, they continued the medication at full dosage; otherwise, the dosage was cut by half. The results: after the first three months, 26 cases significantly improved, 10 improved, and 24 did not respond to the treatment. (24)

Lupus erythematosus:
Lei Gong Teng Pian was used to treat 34 cases of lupus erythematosus. The daily dosage was the equivalent to 20-30 grams of raw herbs. This study reported a total effective rate of 91.5%. (25)

Transplant rejection:
Lei Gong Teng monomer T2 was used to prevent homologuous kidney transplant rejection and its effect was compared with that of azathioprine. The study found that T2 promoted post-transplant recovery and its rejection rate was not significantly different from that of azathioprine. (26)

Hives:
One study treated 30 cases of hives with Lei Gong Teng Pian (20mg each time, three times a day). A comparison group of 30 cases was treated with pyrantel (4mg each time, three times a day). One unit of treatment called for ten consecutive days of treatment. The results after 1-3 units of treatment: the treatment group saw 25 cases significantly improved, 1 improved, and 4 with no effect; the corresponding numbers for the comparison group were 12, 5, and 13 resepctively. (27)
 

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Reference: 

1   Cao Min, et al. Journal of Chinese Patent Medicine. 
     1996;18(4)40-42.
2   Pan Quan Mei. Journal of Applied Nursing. 
     1996;12(1):36-37.
3   Lu Fang, et al. Shanghai Journal of Medicine. 
     1996;19(5):268.
4   Jia Tai He, et al. Journal of Andriatrics. 
     1994;8(4):194-196.
5   Dai Wen Ping, et al. Journal of Chinese Academy of Medical
     Sciences. 1994;16(1):20-30.
6   Wang Bao Jun, et al. Journal of Chinese Academy of Medical
     Sciences. 1992;14(5):357-360.
  Li Hong, et al. Chinese Journal of Pharmacology.
     1997;18(3):270-273.
8   Deng Zhao Zhi, et al. Chinese Journal of Medical Sciences.
     1998;13(3):14-16.
  Fan Zu Sen, et al. Chinese Pharmacology Bulletin. 
     1996;12(6):527-529.
10 Dong Yan Zhang, et al. Journal of Chinese Academy of Medical 
     Sciences. 1993;15(3):193-196.
11 Yu Hai Yan, et al. Chinese Journal of Immunology. 
     1999;15(1):27-28.
12 Liu Shi Xin, et al. Journal of Tongji Medical University. 
     1993;22(2):108-110.
13 Li Xue Wang, et al. Journal of Chinese Academy of Medical Sciences.
     1994;16(6):438-442.
14 Lei Wan Jun, et al. Chinese Journal of Burn an Plastic Surgery. 
     1995;11(4):294-295.
15 Li Ming, et al. Journal of Straits Pharmacy. 
     1999;11(3):27-28.
16 Li Jun, et al. Chinese Pharmacology Bulletin. 
     1994;10(5):345-348.
17 Xu Jing Ya, et al. Chinese Journal of Integrated Medicine. 
     1992;12(3):161-164, 133.
18 Guo Xiao Ming, et al. Journal of No. 3 Military Academy. 
     1999;21(9):627-629.
19 Chen Lin Niu, et al. Jiangsu Journal of Traditional Chinese Medicine. 
     1992;13(6):277-279.
20 Wang Xiao Guang, et al. Journal of Practical Integrated Medicine. 
     1992;5(12):707-709.
21 Liang Xiao Yan, et al. Chinese Journal of Pathology and Physiology. 
     1993;(4):454-457.
22 Wang Jin Ling, et al. Chinese Journal of Integrated Medicine. 
     1992;12(3):185.
23 Wang Hong Zhu, et al. Journal of Practical Integrated Medicine. 
     1992;5(6):331-332.
24 Wu Yao Jiong, et al. Journal of Practical Integrated Medicine. 
     1996;9(4):229-230.
25 Ding Yu Min. Journal of Gansu College of Traditional Chinese 
     
Medicine. 1995;12(2):56-58.
26 Qian Ye Yong, et al. Chinese Journal of Organ Transplantation. 
 
    1993;14 (3):133-135.
27 Xin Li Lin, et al. Shandong Journal of Traditional Chinese Medicine. 
    1996;15(2):56-58.

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Discovery of Molecular Mechanism Reveals Potential Future Cancer Therapy

Researchers at the Johns Hopkins School of Medicine have discovered that a natural product isolated from a traditional Chinese medicinal plant commonly known as thunder god vine, or lei gong teng, and used for hundreds of years to treat many conditions including rheumatoid arthritis works by blocking gene control machinery in the cell. The report, published as a cover story of the March issue of Nature Chemical Biology, suggests that the natural product could be a starting point for developing new anticancer drugs.

“Extracts of this medicinal plant have been used to treat a whole host of conditions and have been highly lauded for anti-inflammatory, immunosuppressive, contraceptive and antitumor activities,” says Jun O. Liu, Ph.D., a professor of pharmacology and molecular sciences at Johns Hopkins. “We’ve known about the active compound, triptolide, and that it stops cell growth, since 1972, but only now have we figured out what it does.”

Triptolide, the active ingredient purified from the plant Tripterygium wilfordii Hook F, has been shown in animal models to be effective against cancer, arthritis and skin graft rejection. In fact, says Liu, triptolide has been shown to block the growth of all 60 U.S. National Cancer Institute cell lines at very low doses, and even causes some of those cell lines to die. Other experiments have suggested that triptolide interferes with proteins known to activate genes, which gives Liu and colleagues an entry point into their research.

The team systematically tested triptolide’s effect on different proteins involved with gene control by looking at how much new DNA, RNA and protein is made in cells. They treated HeLa cells with triptolide for one hour, compared treated to untreated cells and found that triptolide took much longer to have an effect on the levels of newly made proteins and DNA, yet almost immediately blocked manufacture of new RNA. The researchers then looked more closely at the three groups of enzymes that make RNA and found that low doses of triptolide blocked only one, RNAPII.

But the RNAPII enzyme complex actually requires the assistance of several smaller clusters of proteins, according to Liu, which required more investigative narrowing down. Using a small gene fragment in a test tube, the researchers mixed in RNAPII components and in some tubes included triptolide and some not to see which combinations resulted in manufacture of new RNA. Every combination of proteins that included a cluster called TFIIH stopped working in the presence of triptolide.

But again, TFIIH is made of 10 individual proteins, many of which, according to Liu, have distinct and testable activities. Using information already known about these proteins and testing the rest to see if triptolide would alter their behaviors, the research team finally found that triptolide directly binds to and blocks the enzymatic activity of one of the 10, the XPB protein.

“We were fairly certain it was XPB because other researchers had found triptolide to bind to an unknown protein of the same size, but they weren’t able to identify it,” says Liu. “

To convince themselves that the interaction between triplotide and XPB is what stops cells from growing, the researchers made 12 chemicals related to triplotide with a wide range of activity and treated HeLa cells with each of the 12 chemicals at several different doses. By both counting cells and testing XPB activity levels, the team found that the two correlate; chemicals that were better at decreasing XPB activity were also better at stopping cell growth and vice versa.

“Triptolide’s general ability to stop RNAPII activity explains its anti-inflammatory and anticancer effects,” says Liu. “And its behavior has important additional implications for circumventing the resistance that some cancer cells develop to certain anticancer drugs. We’re eager to study it further to see what it can do for future cancer therapy.”

Notes: This research was supported in part by discretionary funds from the Johns Hopkins Department of Pharmacology and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

Authors on the paper include Denis Titov, Qing-Li He, Shridhar Bhat, Woon-Kai Low, Yongjun Dang, Michael Smeaton and Jun O. Liu of Johns Hopkins; Benjamin Gilman, Jennifer Kugel and James Goodrich of the University of Colorado, Boulder; and Arnold Demain of Drew University, Madison, N.J.

Source:
 Audrey Huang
 Johns Hopkins Medical Institutions

Herb extract appears to trigger 'suicide' in cancer cells

By AMY ADAMS                  

STANFORD UNIVERSITY,  Stanford Report, January 16, 2002


People with cancer may find new hope in the form of an old Chinese herb. An extract of the herb, called triptolide, magnifies the effects of traditional chemotherapy — a discovery that earned a patent for Stanford researcher Glenn Rosen, MD. The drug is now in trials to test its safety in cancer patients.

"We are excited about the potential for [the extract] to help patients with solid tumors such as ovarian, breast, lung and colon cancer," said Rosen, who is an associate professor of pulmonary and critical care medicine.

Rosen said that the vine Tripterygium wilfordii has a long history in Chinese medicine. "In china they've been getting an extract of this herb for thousands of years to treat rheumatoid arthritis and other inflammatory diseases," Rosen said. In 1997, Rosen uncovered anti-cancer effects in addition to the herb's traditional use.

Since discovering triptolide's use in treating cancer, the question has been how the extract fights tumors. "We don't know exactly what it does, but we know some pathways that it affects," Rosen said. Those pathways turn out to be ones that are already of keen interest to cancer researchers.

One involves a protein called p53, which acts as a cellular inspector, examining the cell for mutations before allowing it to continue dividing. It works in part by activating another protein called p21, which halts cells before they divide in two.

Some chemotherapy drugs, such as doxorubicin used for treating breast cancer, take advantage of p53 and p21 to stop cancer cells from propagating, but Rosen points out one problem with this strategy. "If the cells stop dividing they can recover and then they can start to proliferate again," Rosen said.

It turns out that triptolide encourages a more permanent solution. When Ke Wei, MD, a postdoctoral fellow in Rosen's lab, exposed cancer cells to a combination of doxorubicin and triptolide, the cells entered a self-induced suicide rather than just pausing in their division. She discovered that cells treated with doxorubicin alone had high levels of p53 and p21, whereas cells treated with both drugs had dramatically lower levels of p21.

What's more, the doses Wei used of both drugs were so low as to be ineffective when she used either drug alone. "The ability for both compounds to work better than either alone at lower doses without increasing toxicity I think will be the major impact of this work," Rosen said. A low dose means fewer side effects such as nausea.

Palo Alto-based Pharmagenesis, where Rosen acts as a consultant, found similar results with a water-soluble form of triptolide. They had tested the compound in combination with low-dose chemotherapy on mice carrying tumors transplanted from humans. Based on the results in Rosen's lab and in mice, Rosen and Pharmagenesis received a patent for triptolide last November, and in December, Pharmagenesis began the first phase of testing the water-soluble form of the extract in humans. "This phase just examines safety and dosing," Rosen said. Within a year, Rosen hopes Stanford will be involved in testing the compound's usefulness in treating cancer patients.

The synergy between triptolide and chemotherapy relies on a functional p53. But many cancers develop mutations in the p53 gene, making them resistant to p53-dependant treatment. Rosen points out, however, that triptolide has potent cancer-killing properties of its own. "Triptolide uses the p53 pathway when it is present, but doesn't need it," he said.

It turns out triptolide interacts with a second pathway that researchers have been investigating for use in cancer treatment. This pathway involves a family of proteins called TNF (tumor necrosis factor). Although TNF can effectively kill cancer cells, it also activates an inflammation-inducing protein. The severe side effects associated with the protein make TNF a problematic treatment. However, when Rosen combines TNF with triptolide, inflammation from the protein all but disappears, and TNF becomes even more effective at driving cancer cells to, in effect, commit suicide. "Again, we see this at low doses," Rosen said. He is optimistic that triptolide may turn out to be a multi-use cancer-fighting agent, effective both in combination with traditional chemotherapy and in tumors that have become resistant to treatment.

                 _____________________________________________________________

This is a link to an study from University of Bologna, Italy: http://www.ncbi.nlm.nih.gov/pubmed/22926559 

Triptolide Induces Pancreatic Cancer Cells Death
Study from University of Minnesota


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Desde la Clinica del Dr. Marcelo Lam/ reportaje para TV: Noticiario de Univison.  
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El Auge de la Medicina Alternativa/ Entrevista a Deepak Chopra. TV SHOW: Oppenheimer Presenta.


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