NF-κB inhibition and PPAR activation by phenolic compounds from hypericum perforatum L. adventitious root

A new compound, perforaphenonoside A (1), along with 11 known compounds (2-12) were isolated from a methanol extract of adventitious roots of Hypericum perforatum. Their chemical structures were elucidated using chemical and physical methods as well as comparison of NMR and mass spectral data with previously reported data. Their inhibition of NF-κB and activation of PPAR was measured in HepG2 cells using a luciferase reporter system. Among the compounds 3, 6, 7 and 12 inhibited NF-κB activation stimulated by TNFα in a dose-dependent manner, with IC₅₀ values ranging from 0.85 to 8.10 μM. Moreover, compounds 1- 3, 7, 11 and 12 activated the transcriptional activity of PPARs in a dose-dependent manner, with EC ₅₀ values ranging from 7.3 to 58.7 μM. The transactivational effects of compounds 1-3, 7, 11 and 12 were evaluated on three individual PPAR subtypes. Among them, compound 2 activated PPARα transcriptional activity, with 153.97% stimulation at 10 μM, while compounds 1, 2 and 11 exhibited transcriptional activity of PPARγ, with stimulation from 124.76% to 126.91% at 10 μM.