Bioactive Glycosylated Flavonoids Exhibiting LXRs Agonist Activity From a Lauraceae Colombian Specie

Lipid metabolism is a vital biological process essential for human health, encompassing key pathways necessary for the survival and homeostasis of all organisms. Liver X Recep-tors (LXRs) are extensively acknowledged as pivotal regulators of lipid homeostasis and inflammatory responses. Pharmacological activation of liver X receptor (LXR) has been shown to increase expression of ApoE and ABCA1 reducing neurodegeneration in murine models of Alzheimer´s disease. Because previous reports determined that Nectandra reticu-lata (Lauraceae) extract has agonistic LXRs activity, the objective of this study was to de-termine the metabolites present in this extract and to evaluate their in silico and in vitro agonistic activity. Identification was done by reversed phase (RP) ultra-high performance liquid chromatography (UHPLC) with a diode array detector (DAD) and high resolution mass spectrometry with electrospray ionization (ESI-HR-MS). In silico study was performed by Auto Dock Vina. The in vitro agonist activity was evaluated using real-time re-verse transcription-polymerase chain reaction (qRT-PCR) to determine the RNA expression of ApoE and ABCA1. The chromatographic analysis revealed the presence of three glycosylated flavonols: The in silico study showed that isolated flavonoids generate a hydrogen bond with T302 and T316 (LXRα and LXRβ respectively). The in vitro study showed that the flavonoids increased the expression of mRNA of both APOE and ABCA1 target genes of LXRs, as observed by qRT-PCR. The bioactive flavonoids isolated in this study possess documented antioxidant effect, when combined with their LXR agonist activity, they become promising bioactive candidates for use in nutraceutical formulations aimed at promoting brain health and anti-inflammatory effects.