J Biol Chem. remission but drug costs are high and are not affordable in all countries. In China an extract of the herb Hook F. (TwHF) is frequently used to treat autoimmune and/or inflammatory diseases due to its favourable costCbenefit ratio. Triptolide has turned out to be the active material of TwHF extracts and has been shown to exert potent anti-inflammatory and immunosuppressive effects and Hook F. (TwHF), also known as Lei Gong Teng, are used as one of the most common systemic treatments for inflammatory and (auto)immune disorders in China mainly due to their favourable costCbenefit ratio. TwHF has been used for centuries in traditional Chinese medicine to treat a variety of immunological disorders, including rheumatoid arthritis, immune complex nephritis and systemic lupus erythematosus. Originally, an extract obtained by boiling the root or leaves of TwHF in water (decoction) was used for systemic treatment. Since a number of adverse effects were observed during therapy the extraction method was changed [3]. With the aim to reduce ZED-1227 toxicity an ethyl acetate extract and a chloroformCmethanol extract (T2) were ZED-1227 developed in the 1970s [4]. Both of these preparations are commercially available in China and have been used extensively meanwhile. The extracts of TwHF contain more than 70 ingredients including diterpenoids, triterpenoids, sesquiterpenoids, -sitosterol, dulcitol and glycosides [5]. Triptolide (C20H24O6, chemical structure see Physique 1) turned out to be the most potent bioactive material in the TwHF extracts. It has been shown to possess potent anti-inflammatory and immunosuppressive properties as well as in different animal models in numerous preclinical studies [6C10]. Besides its use for the treatment of psoriasis, it has been shown that triptolide inhibits experimental autoimmune uveoretinitis and prolongs allograft survival [11, 12]. Moreover, it has been demonstrated that a succinyl derivative of triptolide, PG490-88, can prevent graft Hook F 0.05Azithromycin 500 mg day?1, 2 weeksHang 11%,A24 weeks4 weeks46.51%, 0.05Shen 39.6%, and proliferation of murine lymphocytes was inhibited. However, these derivatives were not as potent as triptolide experimentally [116]. In view of this, several triptolide derivatives with improved water solubility have been developed, like PG490-88, LLDT-8 and F60008. PG490-88 is usually a water-soluble 14-succinyl sodium salt of triptolide which was synthesized in early 2000 (Physique 2). This compound is usually a prodrug of triptolide and is metabolized to triptolide after absorption into the blood. Its anti-inflammatory effects were demonstrated to be comparable with triptolide. An early study showed that intraperitoneal injection of PG490-88 at a dose of 0.25 mg kg?1 day?1 for 2 weeks could attenuate inflammation and fibrosis in the bleomycin model of mouse lung fibrosis [117]. Pan Hook F. Complementary and option therapies for rheumatic diseases II. Rheum Dis Clin North Am. 2000;26:29C50. [PubMed] [Google Scholar] 4. Gutian Hospital and Beisha Hospital FP. Report around the therapeutic effect of the herbal medicine Hook F on reactive status of leprosy [in Chinese] Pi Fu Bing Fang Zhi Tong Xun. 1972;2:29C30. [Google Scholar] 5. Chen BJ. Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Hook F. Leuk Lymphoma. 2001;42:253C65. [PubMed] [Google Scholar] 6. Asano K, Matsuishi J, Yu Y, Kasahara T, Hisamitsu T. Suppressive effects of Hook F, a traditional Chinese medicine, on collagen arthritis in mice. Immunopharmacol. 1998;39:117C26. [PubMed] [Google Scholar] 7. Chang ZED-1227 ML, Yang LL, Chang DM, Kuo SY, Chu SJ. The influence of Chinese traditional medicine around the production and activity of interleukin 1 (IL-1) [in Chinese] Zhonghua Min Guo Wei Sheng Wu Ji Mian Yi Xue Za Zhi. 1993;26:15C24. [PubMed] [Google Scholar] 8. Chang DM, Chang WY, Kuo SY, Chang ML. The effects of traditional antirheumatic herbal medicines on immune response cells. J Rheumatol. 1997;24:436C41. [PubMed] [Google Scholar] 9. Tao X, Schulze-Koops H, Ma L, Cai J, Mao Y, Lipsky PE. Effects of Hook F extracts on induction ZED-1227 of cyclooxygenase 2 activity and prostaglandin E2 production. Arthritis Rheum. 1998;41:130C8. [PubMed] [Google Scholar] 10. Ho LJ, Chang DM, Chang ML, Kuo SY, Lai JH. Mechanism of immunosuppression of the antirheumatic herb TWHf in human T cells. J Rheumatol. 1999;26:14C24. [PubMed] [Google Scholar] 11. Wu Y, Wang Y, Zhong C, Li Y, Li X, Sun B. The suppressive effect of triptolide on experimental autoimmune uveoretinitis by down-regulating Th1-type response. Int Immunopharmacol. 2003;3:1457C65. [PubMed] [Google Scholar] 12. Kupchan SM, Court WA, Dailey RG, Jr, Gilmore CJ, Bryan RF. Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Hook F [in Chinese] 2004. Papers series of the Fourth National Academic Conference of Hook F. 18. Tao XL, Sun Y, Dong Y. A double-blind, controlled trial of glycosides in the treatment of rheumatoid arthritis. Arthritis Rheum. 1987;30:59C9. [Google Scholar] 19. Yu DY. Clinical observation of 144 RFC37 cases of rheumatoid arthritis treated with ZED-1227 glycoside of radix [in Chinese] J.