What is the role of Riccardin F (RF) in modulating the activity of Liver X Receptors (LXRs)?

Riccardin F (RF) is a derivative of Riccardin C, also isolated from the liverwort Blasia pusilla. It shares structural similarities with RC but has different functional properties.

Riccardin F (RF) acts as an LXRα antagonist and does not activate either LXRα or LXRβ-mediated transactivation. RF binds to both LXRα and LXRβ but fails to promote coactivator association, resulting in the inhibition of LXR-mediated gene transcription. In HepG2 cells, RF decreased LXRE-dependent luciferase transcription to the level of endogenous-ligand depletion by compactin, indicating that it competes with endogenous ligands for LXR activation. This suggests that RF can inhibit LXR activity, potentially providing a tool for studying LXR functions and developing LXR modulators.