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Background: Hypercholesterolemia and gut microbiota dysbiosis are associated with the risk of cardiovascular diseases. Hawthorn fruits has shown to be cardioprotective and hypocholesterolemic. However, no studies to date have studied the biological activity of hawthorn seed oil (HSO). The present study was to investigate if HSO could favourably reduce plasma cholesterol and modulate gut microbiota in hypercholesterolemia hamsters. Methods: Golden Syrian hamsters (age, 8 weeks) were randomly divided into five groups (n = 8, each) and fed one of the following five diets, namely a non-cholesterol diet, a high cholesterol diet containing 0.15% cholesterol (HCD); a HCD diet with addition of 4.75% HSO (LHSO), a HCD diet with addition of 9.5% HSO (HHSO), a HCD diet with addition of 0.50% cholestyramine as positive control diet. After 6-week dietary intervention, plasma lipids, inflammatory markers, atherosclerosis plaque, hepatic and fecal lipids were quantified. Microbiota in fresh feces were analysed by sequencing 16S rRNA genes, while RT-PCR and Western blot analyses were employed to quantify the expression of genes involved in cholesterol homeostasis. Results: HSO at a dose of 9.5% HSO could decrease plasma cholesterol and non-HDL-cholesterol by 15%. Additionally, both HSO experimental groups also suppressed mRNA of 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMG-CoA-R). Supplementation of HSO at 4.75% could significantly increase the excretion of fecal acidic sterols, accompanied by elevation of short-chain fatty acid levels in feces. The analyses of gut microbiome indicated that HSO supplementation could selectively alter the genera abundance of gut bacteria that were correlated with cholesterol metabolism including unclassified_f__Christensenellaceae, Ruminococcaceae_NK4A214_ group, norank_o_Gastranaerophilales, Faecalibaculum, Peptococcus, norank_f__Clostridiales_vadinBB60_group and Ruminococcus_2. Conclusions: HSO supplementation was able to decrease plasma cholesterol by favourably modulating gut microbiota composition and gut-derived metabolites associated with cholesterol regulation. [ABSTRACT FROM AUTHOR]

Rutin (R) and quercetin (Q) are two widespread dietary flavonoids. Previous studies regarding the plasma cholesterol-lowering activity of R and Q generated inconsistent results. The present study was therefore carried out to investigate the effects of R and Q on cholesterol metabolism in both HepG2 cells and hypercholesterolemia hamsters. Results from HepG2 cell experiments demonstrate that both R and Q decreased cholesterol at doses of 5 and 10 µM. R and Q up-regulated both the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), low-density lipoprotein receptor (LDLR), and liver X receptor alpha (LXRα). The immunofluorescence study revealed that R and Q increased the LDLR expression, while only Q improved LDL-C uptake in HepG2 cells. Results from hypercholesterolemia hamsters fed diets containing R (5.5 g/kg diet) and Q (2.5 g/kg diet) for 8 weeks demonstrate that both R and Q had no effect on plasma total cholesterol. In the liver, only Q reduced cholesterol significantly. The discrepancy between the in vitro and in vivo studies was probably due to a poor bioavailability of flavonoids in the intestine. It was therefore concluded that R and Q were effective in reducing cholesterol in HepG2 cells in vitro, whereas in vivo, the oral administration of the two flavonoids had little effect on plasma cholesterol in hamsters. [ABSTRACT FROM AUTHOR]