1,6-O,O-diacetylbritannilactones inhibits IκB kinase β-dependent NF-κB activation

摘要: Abstract To determine the chemical constituents responsible for pharmacological effects of Inula britannica-F., three specific sesquiterpene lactones in britannica were isolated from chloroform extract and identified, including britannilactone (BL), 1-O-acetylbritannilactone (ABLO), 1,6-O,O-diacetylbritannilactone (ABLOO). Electrophoretic mobility shift assay (EMSA) was performed to detect nuclear translocation factor-κB (NF-κB) p65. The expressions IκBα, pIκBα, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), IκB kinase α/β (IKKα/β) NF-κB (NIK) detected by Western blot RT-PCR. We found that acetyl side groups enhanced inhibitory action agents on LPS/IFN-γ-induced iNOS COX-2 expression. Their inhibiting activity positive correlation with group number. LPS/IFN-γ reversed ABLOO, BL without showed only a weak action. Further study indicated ABLOO markedly inhibited phosphorylation IKKβ down based level, but not IKKα, corresponding decreased IκBα degradation induced LPS/IFN-γ, resulting suppression activity. These results suggest moieties add lipophilicity, consequently enhance cellular penetration, so possess most anti-inflammatory effect may be potent lead structure development therapeutic cytokine-suppressing remedies valuable treatment various inflammatory diseases.