New Sesquiterpenoids from the Mangrove-Derived Fungus Talaromyces sp. as Modulators of Nuclear Receptors

Four new sesquiterpenoids, talaroterpenes A–D (1–4), were isolated from the mangrove-derived fungus Talaromyces sp. SCSIO 41412. The structures of compounds 1–4 were elucidated through comprehensive NMR and MS spectroscopic analyses. The absolute configurations of 1–4 were assigned based on single-crystal X-ray diffraction and calculated electronic circular dichroism analysis. Talaroterpenes A–D (1–4) were evaluated with their regulatory activities on nuclear receptors in HepG2 cells. Under the concentrations of 200 μM, 1, 3 and 4 exhibited varying degrees of activation on ABCA1 and PPARα, while 4 showed the strongest activities. Furthermore, 4 induced significant alterations in the expression of downstream target genes CLOCK and BMAL1 of RORα, and the in silico molecular docking analysis supported the direct binding interactions of 4 with RORα protein. This study revealed that talaroterpene D (4) was a new potential non-toxic modulator of nuclear receptors.