Multimolecular interactions from Chinese medicines activate nuclear receptor conformational changes: a potential strategy for anti-inflammatory therapy.

Nuclear receptors (NRs) are among the most common transcriptional regulators in the human body. Currently, liver X receptor (LXR), pregnane X receptor (PXR), farnesoid X receptor (FXR), and peroxisome proliferator-activated receptor (PPAR) are significant targets in the management of inflammatory metabolic disorders. Traditional Chinese medicine has shown good results in treating inflammatory metabolic diseases, but no one has yet summarized the mechanism of action of Chinese medicine monomers on these four NRs. This article summarizes the key binding sites for endogenous agonists and Chinese medicine monomers with NRs, as well as the patterns of NR conformational changes after interaction. This provides a basis for future structural research in the development and optimization of Chinese medicine medicines. We found that the same Chinese medicine monomer can act on different NRs and exert different physiological functions and that the same NR can be activated by different Chinese medicine monomers. This holistic nature is highly compatible with the multicomponent and multi-targeted therapeutic effects of Chinese medicines, making the development of NR-based drugs feasible.