Engelheptanoxides behave as liver X receptor α agonists

Engelheptanoxide A and C are the active ingredients isolated from Engelhardia roxburghiana, a novel traditional herbal medicine exerting pharmacological effects including the antitubercular effect. Liver X receptor (LXR) acts as a ligand-activated transcription factor that can exert multi-pharmacological functions. In this study, the activity of engelheptanoxide A and C against LXR alpha was evaluated by the transient transfection reporter and mammalian one-hybrid assays. The results showed that engelheptanoxide A and C respectively transactivated CYP7A1, ABCA1, and Gal4 promoters in the dose-dependent manner. Furthermore, the docking study demonstrated that engelheptanoxide A and C can contact with the LXR alpha ligand binding pocket in the similar manner as 22(R)-hydroxycholesterol, an endogenous LXR alpha agonist, to agonize LXR alpha. These results indicated that Engelhardia roxburghiana might be able to exert pharmacological effects through LXR alpha pathway.