Abstract
Nuclear receptors (NRs) are a superfamily of transcription factors induced by ligands and also function as integrators of hormonal and nutritional signals. Among NRs, the liver X receptors (LXRs) and farnesoid X receptor (FXR) have been of significance as targets for the treatment of metabolic syndrome-related diseases. In recent years, natural products targeting LXRs and FXR have received remarkable interests as a valuable source of novel ligands encompassing diverse chemical structures and bioactive properties. This review aims to survey natural products, originating from terrestrial plants and microorganisms, marine organisms, and marine-derived microorganisms, which could influence LXRs and FXR. In the recent two decades (2000–2020), 261 natural products were discovered from natural resources such as LXRs/FXR modulators, 109 agonists and 38 antagonists targeting LXRs, and 72 agonists and 55 antagonists targeting FXR. The docking evaluation of desired natural products targeted LXRs/FXR is finally discussed. This comprehensive overview will provide a reference for future study of novel LXRs and FXR agonists and antagonists to target human diseases, and attract an increasing number of professional scholars majoring in pharmacy and biology with more in-depth discussion.
Highlights
Nuclear receptors (NRs), a superfamily of transcription factors incorporating a group of members in humans and in mice (Gronemeyer et al, 2004; Zhang et al, 2004), are integrators of hormonal and nutritional signals, mediating changes to metabolic pathways within the body (Calkin and Tontonoz, 2012)
This review focuses on natural products targeting liver X receptors (LXRs)/farnesoid X receptor (FXR)
In the recent two decades (2000–2020), 261 natural products were discovered from natural resources, such as LXRs/FXR modulators, 109 agonists and 38 antagonists targeting LXRs, while 72 agonists and 55 antagonists are targeting FXR
Summary
Nuclear receptors (NRs), a superfamily of transcription factors incorporating a group of members in humans and in mice (Gronemeyer et al, 2004; Zhang et al, 2004), are integrators of hormonal and nutritional signals, mediating changes to metabolic pathways within the body (Calkin and Tontonoz, 2012). LXRα consists of 447 amino acids and is highly expressed in the liver, whereas LXRβ consists of 460 amino acids and is expressed ubiquitously in most tissues and organs (Apfel et al, 1994; Shinar et al, 1994; Willy et al, 1995; Lu et al, 2001; Chinetti-Gbaguidi and Staels, 2009) Both LXRα and LXRβ form obligate heterodimers with 9-cis retinoic acid receptor RXR (retinoid X receptor, NR2B1), and LXRs/RXR might be activated by ligands for either LXRs or RXR, such as endogenous oxysterols for LXRs, which are considered as “permissive” (Chinetti-Gbaguidi et al, El-Gendy et al, 2018). For a brief background of LXRs/FXR, we refer to several recent reviews and give comprehensive overviews regarding this topic, and the docking evaluation of desired natural products targeting LXRs/FXR is discussed
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