Triptolide

Triptolide (CAS 38748-32-2) is a major bioactive constituent extracted from the traditional Chinese medicine Tripterygium wilfordii and is an inhibitor of IL-2/MMP-3/MMP-7/MMP-19. It is commonly used to establish triptolide-induced acute liver injury models for evaluating hepatoprotective drugs.

Triptolide inhibits IL-2 expression in activated T cells and NF-kappaB-mediated transcriptional activation [1]. At very low concentrations, triptolide also inhibits colony formation and tumor cell proliferation.

Administration of 15 nM triptolide inhibits the invasion and migration of ovarian cancer cells SKOV3 and A2780. At concentrations of 0-15 nM, triptolide dose-dependently inhibits MMP7 and MMP19 expression in ovarian cancer cells. Triptolide also enhances E-cadherin expression in ovarian cancer cells, thereby affecting migration and cell invasion [2]. At a minimum dose of 100 nM, triptolide dose-dependently reduces Rpb1, leading to a significant decrease in RNAPII in SKOV3 cells [3]. In rheumatoid synovial fibroblasts (RSF), triptolide dose-dependently decreases cell viability (IC50 = 74.3 nM) while inhibiting cell proliferation (IC50 = 20.4 nM). Administration of triptolide (100 nM) for 24 hours significantly alters synovial cell morphology [4]. At concentrations of 10-100 ng/ml, triptolide induces apoptotic death of peripheral T cells and T-cell hybrids by increasing DEVD-cleaved caspase activity [5].

In primary human synovial fibroblasts, SW1353 cells, and human osteoarthritic chondrocytes, 125-150 nM triptolide inhibits cytokine-induced MMP-3 expression, thereby preventing aggrecanase- and MMP-driven cartilage degradation [6].

References: [1]. Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC, Kao PN: Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem 1999, 274(19):13443-13450.

[2]. Zhao H, Yang Z, Wang X, Zhang X, Wang M, Wang Y, Mei Q, Wang Z: Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin. Exp Mol Med 2012, 44(11):633-641.

[3]. Manzo SG, Zhou ZL, Wang YQ, Marinello J, He JX, Li YC, Ding J, Capranico G, Miao ZH: Natural product triptolide mediates cancer cell death by triggering CDK7-dependent degradation of RNA polymerase II. Cancer Res 2012, 72(20):5363-5373.

[4]. Kusunoki N, Yamazaki R, Kitasato H, Beppu M, Aoki H, Kawai S: Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts. BMC Pharmacol 2004, 4:2.

[5]. Yang Y, Liu Z, Tolosa E, Yang J, Li L: Triptolide induces apoptotic death of T lymphocyte. Immunopharmacology 1998, 40(2):139-149.

[6]. Liacini A, Sylvester J, Zafarullah M: Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes. Biochem Biophys Res Commun 2005, 327(1):320-327.