The Flavone Luteolin Inhibits Liver X Receptor Activation

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2016-05, Vol.79 (5), p.1423-1428
• Main Authors: Francisco, Vera, Figueirinha, Artur, Costa, Gustavo, Liberal, Joana, Ferreira, Isabel, Lopes, Maria C, García-Rodríguez, Carmen, Cruz, Maria T, Batista, Maria T
• Format: Article
• Language: English
• Subjects: Antioxidants - pharmacology; Cell Survival - drug effects; Flavones - pharmacology; Hep G2 Cells; Hepatocytes - drug effects; Humans; Lipid Metabolism; Liver - drug effects; Liver X Receptors - antagonists & inhibitors; Luteolin - chemistry; Luteolin - pharmacology; Molecular Structure; Polymerase Chain Reaction; Sterol Regulatory Element Binding Protein 1 - drug effects
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.6b00146

Luteolin is a dietary flavonoid with medicinal properties including antioxidant, antimicrobial, anticancer, antiallergic, and anti-inflammatory. However, the effect of luteolin on liver X receptors (LXRs), oxysterol sensors that regulate cholesterol homeostasis, lipogenesis, and inflammation, has yet to be studied. To unveil the potential of luteolin as an LXRα/β modulator, we investigated by real-time RT-PCR the expression of LXR-target genes, namely, sterol regulatory element binding protein 1c (SREBP-1c) in hepatocytes and ATP-binding cassette transporter (ABC)­A1 in macrophages. The lipid content of hepatocytes was evaluated by Oil Red staining. The results demonstrated, for the first time, that luteolin abrogated the LXRα/β agonist-induced LXRα/β transcriptional activity and, consequently, inhibited SREBP-1c expression, lipid accumulation, and ABCA1 expression. Therefore, luteolin could abrogate hypertriglyceridemia associated with LXR activation, thus presenting putative therapeutic effects in diseases associated with deregulated lipid metabolism, such as hepatic steatosis, cardiovascular diseases, and diabetes.