Filicinic acid based meroterpenoids from Hypericum elodeoides and their anti-Alzheimer’s disease effects

(±)-Elodeoidileons A-L (1–12), 12 pairs of previously undescribed filicinic acid based meroterpenoids were isolated from Hypericum elodeoides with unique linear or angular 6/6/6 ring core. Modern spectroscopic techniques, modified Mosher’s method and quantum chemical calculations were used to identify the planner structures and configurations of 1–12. Additionally, the potential biosynthetic pathways for 1–12 were anticipated. Moreover, biological activity assessments suggested that 1a, 5a, and 11b could activate Retinoid X receptor-α (RXRα) transcription and enhance the ATP-binding cassette transporter A1 (ABCA1) protein’s expression. Fluorescence titration assay suggested that 1a might have a direct interaction with the RXRα-LBD protein, with an estimated K_d value of 5.85 μM. Moreover, molecular docking study confirmed the binding of 1a to RXRα and further validated by cellular thermal shift assay (CETSA). Thus, compound 1a may promote β-amyloid (Aβ) clearance by targeting RXRα and upregulating the expression of the ABCA1 protein, showing promise as anti-Alzheimer’s agent.