ArticleScientific reports2025
Saffron as a natural modulator of reverse cholesterol transport genes in atherosclerotic rabbits, with molecular docking insights.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Atherosclerosis is a major contributor to cardiovascular disease, and one of the mechanisms that contributes to atherosclerosis is the reverse cholesterol transport (RCT) pathway, which includes SR-BI, ABCA1, and PPARγ genes. Natural compounds that modulate RCT-related genes may present promising therapeutic alternatives. Saffron (Crocus sativus L.), rich in bioactive carotenoids, exhibits both lipid-lowering and antioxidant properties. This study investigated the effects of saffron extract on hepatic expression of SR-BI, ABCA1, and PPARγ genes in the atherosclerotic rabbit model and evaluated the molecular docking of its major phytocompounds. Fifty-five male New Zealand White rabbits (NZWR) were randomly assigned to three main groups: a normal diet (ND) group, a 1% high-cholesterol diet (HCD; 4 W, 8 W) group, and intervention groups. Rabbits in the HCD and intervention groups were induced for early atherosclerosis (4 weeks) and established atherosclerosis (8 weeks). Following these induction periods, each subgroup received 8 weeks of oral treatment with saffron ethanolic extract (50 or 100 mg/kg/day), statin (2.5 mg/kg/day), or placebo while maintained on a normal chow diet. The Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis showed that saffron treatment significantly upregulated hepatic SR-BI expression in early atherosclerosis (S50: 3.65-fold, p < 0.05; S100: 4.59-fold, p < 0.05) and in established atherosclerosis (S100: 8.34-fold, p < 0.01). ABCA1 and PPARγ expression levels were also increased, though not statistically significant. Molecular docking demonstrated favorable binding affinities between saffron bioactives and RCT-related targets, with crocetin (a major carotenoid compound in saffron) binding to PPARγ (–7.75 kcal/mol) and SR-BI (–7.24 kcal/mol), and quercetin binding to ABCA1 (–8.35 kcal/mol). These findings suggest that saffron may positively modulate RCT-associated gene expression, supporting its potential as a natural adjunct in atherosclerosis research and management.
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