Intraperitoneal Isoastragaloside II Attenuated Western Diet-Induced Atherosclerosis in Male ApoE-/- Mice with Lipid-Lowering and Anti-Inflammatory Effects.

Background

Atherosclerosis is driven by lipid accumulation, vascular inflammation, and macrophage foam cell formation. Nutritional therapy, employing natural products with bioactive compounds, is a potential avenue for treating atherosclerosis. Isoastragaloside II (Iso-AS-II) is a bioactive saponin isolated from the medicinal and edible plant Astragalus membranaceus (Huangqi), but its role in atherosclerosis has not been investigated.

Methods

In this study, we investigated the effects of Iso-AS-II (i.p., 5 mg/kg) in male ApoE-/- mice fed a Western diet (WD) and identified potential mechanisms through network pharmacology and transcriptomic analyses. In parallel, oxidized low-density lipoprotein (ox-LDL)-induced RAW 264.7 foam cells were used to evaluate the efficacy of Iso-AS-II in reducing foam cell accumulation and inflammation.

Results

Iso-AS-II reduced aortic lesion area, plaque macrophage infiltration, and smooth muscle cell content, and lowered serum lipids (TC, TG and LDL-C) and inflammatory cytokines (TNF-α, IL-6, MCP-1, M-CSF and IL-12). Network pharmacology and transcriptomics suggested modulation of lipid metabolism and inflammatory pathways. In macrophages, Iso-AS-II suppressed foam cell formation, accompanied by downregulation of Cd36 and Msr1 and upregulation of Abca1 and Abcg1, and exerted anti-inflammatory effects by reducing IL-1β, IL-6, and TNF-α levels.

Conclusions

This exploratory study provides the first evidence that Iso-AS-II reduces atherosclerotic burden in WD-fed ApoE-/- mice, and suggests that these effects involve improved systemic lipid homeostasis, suppression of inflammation, and inhibition of macrophage foam-cell formation, supporting its potential as a natural anti-atherosclerotic agent.