Engelheptanoxides behave as liver X receptor α agonists

• Published in: Medicinal chemistry research 2023-03, Vol.32 (3), p.434-441
• Main Authors: Liang, Yu-Hsuan, Luo, Yu-Han, Chen, Ih-Sheng, Lin, Hsiang-Ru
• Format: Article
• Language: English
• Subjects: ABCA1 protein; Agonists; ATP-binding protein; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Brief Report; Engelhardia roxburghiana; Herbal medicine; Inorganic Chemistry; Ligands; Liver; Liver X receptors; Medicinal Chemistry; Pharmacology; Pharmacology/Toxicology; Receptors; Transfection
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-023-03016-y

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 LXRα 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 LXRα ligand binding pocket in the similar manner as 22(R)-hydroxycholesterol, an endogenous LXRα agonist, to agonize LXRα. These results indicated that Engelhardia roxburghiana might be able to exert pharmacological effects through LXRα pathway.