Effects of citrus flavonoids, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone and 3,5,6,7,8,3′,4′-heptamethoxyflavone, on the activities of macrophage scavenger receptors and the hepatic LDL receptor

Mei-Chun Kou; Shih-Hang Fu; Jui-Hung Yen; Ching-Yi Weng; Shiming Li; Chi-Tang Ho; Ming-Jiuan Wu

doi:10.1039/C3FO30301B

Effects of citrus flavonoids, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone and 3,5,6,7,8,3′,4′-heptamethoxyflavone, on the activities of macrophage scavenger receptors and the hepatic LDL receptor†

Mei-Chun Kou,‡^a Shih-Hang Fu,‡^a Jui-Hung Yen,^b Ching-Yi Weng,^a Shiming Li,^c Chi-Tang Ho^c and Ming-Jiuan Wu*^a

* Corresponding authors

^a Department of Biotechnology, Chia Nan University of Pharmacy and Science, Tainan 717, Taiwan
E-mail: imwu@mail.chna.edu.tw
Fax: +886-6-266-2135
Tel: +886-6-266-4911 ext. 2520

^b Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970, Taiwan
E-mail: imyenjh@hotmail.com

^c Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901-8520, USA
E-mail: ho@aesop.rutgers.edu

Abstract

Epidemiological and animal studies point to a possible protective effect of citrus flavonoids against cardiovascular diseases. The aim of this study is to investigate the effects of citrus flavonoids, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone (5-OH-HxMF) and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HpMF), on the activities and expressions of macrophage scavenger receptors and the hepatic LDL receptor. Treatment of HpMF (20 μM) during THP-1 differentiation successfully attenuated 12-myristate 13-acetate (PMA)-mediated DiI-labeled oxidized low-density lipoprotein (oxLDL) uptake as evidenced by flow cytometry, indicating that the functions of scavenger receptors were blocked. RT-Q-PCR analysis suggests that the decrease in oxLDL uptake was due to the down-regulation of PMA-induced SR-A mRNA expression. In terminally differentiated THP-1 macrophages, 5-OH-HxMF and HpMF could significantly reduce DiI-oxLDL uptake, with the former having a greater effect. 5-OH-HxMF attenuated oxLDL-mediated CD36 and SR-A expression; while HpMF only decreased CD36 expression. The effects of these two flavonoids on the activity and expression of the hepatic LDL receptor (LDLR) were further investigated in HepG2 cells. 5-OH-HxMF (10–20 μM) enhanced DiI-LDL uptake by 1.33-fold due to the enhanced LDLR expression. These results imply that HpMF is better at inhibiting PMA-induced oxLDL uptake during THP-1 differentiation, while 5-OH-HxMF is more powerful in attenuating oxLDL-induced scavenger receptor expression and activity in terminally differentiated THP-1 macrophages. Furthermore, 5-OH-HxMF may have hypolipidemic activity due to its up-regulating hepatic LDLR expression.

Food & Function

Effects of citrus flavonoids, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone and 3,5,6,7,8,3′,4′-heptamethoxyflavone, on the activities of macrophage scavenger receptors and the hepatic LDL receptor†

Abstract

Supplementary files

Article information

Download Citation

Permissions

Effects of citrus flavonoids, 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone and 3,5,6,7,8,3′,4′-heptamethoxyflavone, on the activities of macrophage scavenger receptors and the hepatic LDL receptor

Social activity

Search articles by author

Spotlight

Advertisements