Immunosuppressive and Anti-Inflammatory Mechanisms of Triptolide, the Principal Active Diterpenoid from the Chinese Medicinal Herb Tripterygium wilfordii Hook. f.

Abstract

Extracts of Tripterygium wilfordii hook. f. (leigong teng, Thundergod vine) are effective in traditional Chinese medicine for treatment of immune inflammatory diseases including rheumatoid arthritis, systemic lupus erythematosus, nephritis and asthma. Characterisation of the terpenoids present in extracts of Tripterygium identified triptolide, a diterpenoid triepoxide, as responsible for most of the immunosuppressive, anti-inflammatory and antiproliferative effects observed in vitro. Triptolide inhibits lymphocyte activation and T-cell expression of interleukin-2 at the level of transcription. In all cell types examined, triptolide inhibits nuclear factor-kappaB transcriptional activation at a unique step in the nucleus after binding to DNA. Further characterisation of the molecular mechanisms of triptolide action will serve to elucidate pathways of immune system regulation.

Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae)

“…Extracts also performed well in animal models of rheumatoid arthritis (Tao and Lipsky, 2000), including collagen-induced arthritis in mice (Gu et al, 1992), adjuvant-induced arthritis in rats Hu et al, 2003), and arthritis that develops spontaneously in HLA-B27 transgenic rats . Tripterygium extracts were also effective in a mouse model of graft-vs.-host disease, an immunological reaction to foreign tissue , and in studies with allografts, transplants of tissue from a genetically similar donor (reviewed by Qiu and Kao, 2003).…”

“…Pure triptolide (1) has also shown significant activity in animal models including the adjuvant-induced arthritis model and allograft models (reviewed by Qiu and Kao, 2003;Zhu et al, 2004). Compounds related to 1 are currently being evaluated for use in organ transplantation (First and Fitzsimmons, 2004).…”

“…Most of the antiinflammatory and immunosuppressive activities of extracts can be attributed to triptolide (1). The clinical and pharmacological effects of triptolide (1) have been reviewed recently Qiu and Kao, 2003;Zhu et al, 2004;Liu et al, 2005). However, several other compounds present in Tripterygium may contribute to the biological activity of the extracts and may substantially modify the effects of triptolide (1).…”

“…Therefore, the efficacy of these extracts in disease treatment may be greater than that of triptolide (1) alone, due to additive or even synergistic effects between different compounds in the extracts, for example with tripdiolide (31). This review summarizes the pharmacology of Tripterygium extracts, a topic discussed in more detail elsewhere (Tao and Lipsky, 2000;Qiu and Kao, 2003;Ho and Lai, 2004), and discusses related activities exhibited by other compounds found in this genus.…”

ATF2 contributes to cisplatin resistance in non‐small cell lung cancer and celastrol induces cisplatin resensitization through inhibition of JNK/ATF2 pathway

“…It is active against rheumatoid arthritis, 11 allergic asthma 12 and systemic lupus erythematosus. 13 In several cancer models, both in vitro and in vivo, …”