TLR‐pathway is involved in the biological activity of triptolide, the active compound from a botanical clinically shown to alleviate RA symptoms

Triptolide is a diterpene triepoxide present in roots of Tripterygium wilfordii Hook F., with known anti‐inflammatory, immunosuppressive and anti‐cancer properties. Although it is known that triptolide inhibits NFκB activation downstream of TLRs, involvement of TLR cascade in triptolide activity was not reported. Objective of the study was to investigate if triptolide suppresses expression of proinflammatory downstream effectors induced specifically by different TLR agonists. The results suggest that the suppression of agonist‐induced NFκB activation and chemokine expression by triptolide is mediated by targeting the early signaling of TLRs, particularly that of TLR4 in RAW 264.7 cells. Triptolide down regulated the expression of TLR4 proteins and that of TRIF adapter proteins in MyD88‐independent pathway of TLR4. In addition gene expression profiles in response to triptolide treatment suggest that triptolide may have multiple cellular targets contributing to its strong anti‐inflammatory and immune suppressive properties. This study reveals involvement of TLR signaling in triptolide activity and further increases understanding of how triptolide activity may down regulate NFκB activation during inflammatory conditions. Funding for this research came from multiple grants by National Institutes of Health, Bethesda, MD [to MD and IR] and in parts by Phytomedics Inc., Jamesburg, NJ [to IR].