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ID: ALA4033685

Journal: Bioorg Med Chem

Title: C21-steroidal pregnane sapogenins and their derivatives as anti-inflammatory agents.

Authors: Huang LJ, Chen SR, Yuan CM, Gu W, Guo BJ, Wang YT, Wang Y, Hao XJ.

Abstract: During the screening of natural anti-inflammatory agent, we identified some C21-steroidal pregnane sapogenins or the derivatives to inhibit TLR2, TLR3, and TLR4-initiatedinflammatory responses respectively. Treatment with active compounds 10, 2j and 3p failed to impact tumor necrosis factor-α (TNF-α) induced nucleus translocation of NF-κB p65 subunit. However, these compounds regulated distinct canonical or non-canonical NF-κB family members. Ectopic expression of TNF receptor associated factor 6 (TRAF6) abrogated the inhibitory activity of the compounds on production of pro-inflammatory cytokines downstream of TLR4. These results suggested that compounds 10, 2j, and 3p suppressed TLR-initiated innate immunity through TRAF6 with differential regulation of NF-κB family proteins.

CiteXplore: 28506585

DOI: 10.1016/j.bmc.2017.04.045