{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:59:22Z","timestamp":1790312362010,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province","id":[{"id":"https:\/\/ror.org\/01cvdks57","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01cvdks57","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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-\u03b1, 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-1\u03b2, IL-6, and TNF-\u03b1 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.<\/jats:p>","DOI":"10.3390\/nu18193137","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:10:31Z","timestamp":1790179831000},"page":"3137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intraperitoneal Isoastragaloside II Attenuated Western Diet-Induced Atherosclerosis in Male ApoE-\/- Mice with Lipid-Lowering and Anti-Inflammatory Effects"],"prefix":"10.3390","volume":"18","author":[{"given":"Jian","family":"Ai","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haorui","family":"Ma","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deshan","family":"Ning","sequence":"additional","affiliation":[{"name":"Infinitus (China) Company Ltd., Guangzhou 510405, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Infinitus (China) Company Ltd., Guangzhou 510405, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyong","family":"Mao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2080-2214","authenticated-orcid":false,"given":"Qiuxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumao","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"Wuxi Institute for Specialized Nutrition and Health Co., Ltd., Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1016\/j.jacc.2025.08.015","article-title":"Global, Regional, and National Burden of Cardiovascular Diseases and Risk Factors in 204 Countries and Territories, 1990\u20132023","volume":"86","author":"Stark","year":"2025","journal-title":"Jacc-J. 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