The modulation of PCSK-9 and GAGs by 10-dehydrogingerdione and pentoxifylline in hyperlipidemic rabbits

Abstract

The hypolipidemic effect of 10-DHGD was previously reported owing to its anti-inflammatory and anti-oxidant properties. We further investigated the anti-inflammatory role of 10-DHGD in modulating atherogenicity by targeting proproteinconvertasesubtilisinkexin-9 (PCSK-9). Rabbits fed high cholesterol diet (HCD) containing 0.2% w/w cholesterol for12-weeks received either 10-DHGD (10-mg/kg), pentoxifylline (PTX, 40-mg/kg) or their combination concurrently with HCD. Lipid profile, serum PCSK-9, macrophage migration inhibitory factor (MIF), aorta tumor necrosis factor- alpha (TNF-α) and glycosaminoglycans (GAGs) were measured. Atherogenicity and increased PCSK-9, MIF and TNF-α and GAGs (p < 0.001) was proved HCD-fed rabbits. The concurrent administration of 10-DHGD or PTX with HCD feeding prevented this atheogenicity by modulating the release of PCSK-9, inflammatory markers and GAGs. The combined PTX and 10-DHGD in HCD fed rabbits not only lowered hyperlipidemia, but also targeted arterial inflammation to a better extent. In conclusion PTX and 10-DHGD can prevent hyperlipidemia and associated inflammatory process modifying factors predisposing to atherosclerosis.

Graphical Abstract

Keywords:

• Hyperlipidemia
• PCSK-9
• GAGs
• 10- Dehydrogingerdione
• pentoxifylline