Wedelolactone is an inhibitor of IKK.

IkB kinase (IKK) complex contains the catalytic subunits IKKα and IKKβ, and the regulatory subunit IKKγ/NEMO. IKK, is a kinase critical for activation of NF-κB by mediating phosphorylation and degradation of IκBα. The induction of caspase-11 is an important upstream controlling event in inflammatory response and apoptosis under pathological conditions modulated by upstream NF-κB-mediated transcription[1].

In vitro: In cultured mouse BALB/c 3T3 cells, mouse splenocytes and HeLa cells, wedelolactone (0~100 μM) inhibited LPS-induced caspase-11 expression by inhibiting NF-κB-mediated transcription through the direct inhibition of IKK. Wedelolactone played an potential role in anti-inflammatory therapy to inhibit IL-1β levels in diseases such as rheumatoid arthritis, asthma and septic shock[1].

In vivo: On Swiss albino male mouse skin, IKK inhibition by wedelolactone (10 μM) prevented the induction of NF-κB, perturbed the generation of reactive oxygen species and reactive nitrogen intermediates, blunted the signal transduction that lead to the activation of the early immediate genes, and thereby protected mouse skin from the UVB induced neoplastic transformation, angiotropism and metastatic progression [2].