Investigating the anti-atherosclerotic effects and potential mechanism of Dalbergia odorifera in ApoE-deficient mice using network pharmacology combined with metabolomics.

Dalbergia odorifera (DO) is a precious rosewood species in Southern Asia, and its heartwood is used in China as an official plant for invigorating blood circulation and eliminating stasis. This study aims to evaluate the efficacy of DO on atherosclerosis (AS), and further explore its active components and potential mechanisms. The apolipoprotein-E (ApoE)-deficient mice fed a high-fat diet were used as model animals, and the pathological changes in mice with or without DO treatment were compared to evaluate the pharmacodynamics of DO on AS. The mechanisms were preliminarily expounded by combining with metabolomics and network pharmacology. Moreover, the bioactive components and targets were assessed by cell experiments and molecular docking, respectively. Our findings suggested that DO significantly modulated blood lipid levels and alleviated intimal hyperplasia in atherosclerotic-lesioned mice, and the mechanisms may involve the regulation of 18 metabolites that changed during the progression of AS, thus affecting 3 major metabolic pathways and 3 major signaling pathways. Moreover, the interactions between 16 compounds with anti-proliferative effect and hub targets in the 3 signaling pathways were verified using molecular docking. Collectively, our findings preliminarily support the therapeutic effect of DO in atherosclerosis, meanwhile explore the active constituents and potential pharmacological mechanisms, which is conducive to its reasonable exploitation and utilization.

Tanshinone IIA-Loaded Micelles Functionalized with Rosmarinic Acid: A Novel Synergistic Anti-Inflammatory Strategy for Treatment of Atherosclerosis.

Rosmarinic acid (RA) and tanshinone IIA (TA) which are effective components in Salvia miltiorrhiza show anti-inflammatory potential against atherosclerosis. Based on polysulfated propylene-polyethylene glycol (PPS-PEG), RA was grafted onto this polymer via amide bonds to form a micelle carrier for TA encapsulation: PPS-PEG-RA@TA. A potent inhibitory effect on lipopolysaccharide (LPS) -induced proliferation of endothelial cells with significant intracellular uptake was observed with this system. This could have been the result of release of TA in a reactive oxygen species (ROS) environment and stronger antioxidant effect of RA. The synergistic effect was optimized when the combination was used in a molar ratio of 1:1. Mechanistic studies showed that, compared with PPS-PEG-RA and TA+RA, PPS-PEG-RA@TA micelles could more effectively regulate the nuclear factor-kappa B (NF-κB) pathway to reduce expression of vascular cell adhesion molecule-1 (VCAM-1), inhibit the inflammatory cascade and reduce endothelial-cell injury. One month after intravenous injection of PPS-PEG-RA@TA micelles, the plaque area in murine aortic vessels was reduced significantly, and serious toxic side-effects were not observed in vivo, along with excellent biocompatibility. In summary, PPS-PEG-RA@TA micelles could achieve synergistic treatment of atherosclerosis.

Supplementation of Bacillus sp. DU-106 reduces hypercholesterolemia and ameliorates gut dysbiosis in high-fat diet rats.

Gut microbiota modulation by a probiotic is a novel therapy for hypercholesterolemia mitigation. This study initially investigated the potential hypocholesterolemic effect of Bacillus sp. DU-106 in hypercholesterolemic rats and explored its potential relation with gut microbiota. Sprague-Dawley rats received a high-fat diet, or a high-fat diet supplemented with 7.5 × 109 and 1.5 × 1010 CFU/kg bw/day Bacillus sp. DU-106 (low-dose and high-dose groups). At the end of 9 weeks, Bacillus sp. DU-106 treatment significantly decreased the body weight, liver index, and total cholesterol. 16S rRNA sequencing showed that Bacillus sp. DU-106 intervention significantly increased bacterial richness and particularly increased the genus abundance of Turicibacter, Acinetobacter, Brevundimonas, and Bacillus and significantly decreased the abundance of Ralstonia. Metabolomic data further indicated that the supplementation of Bacillus sp. DU-106 remarkably changed the gut metabolic profiles of hypercholesterolemic rats and, in particular, elevated the metabolites of indole-3-acetate, methylsuccinic acid, creatine, glutamic acid, threonine, lysine, ascorbic acid, and pyridoxamine. Spearman's correlation analysis showed the close relation between the different genera and metabolites. In conclusion, Bacillus sp. DU-106 supplement ameliorated high-fat diet-induced hypercholesterolemia and showed potential probiotic benefits for the intestine. KEY POINTS: • A novel potential probiotic Bacillus sp. DU-106 ameliorated hypercholesterolemia in rats. • Bacillus sp. DU-106 supplement regulated gut microbiome structure and richness. • Bacillus sp. DU-106 supplement changed metabolic profiles in high-fat diet rats. • Significant correlations were observed between differential genera and metabolites.