{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:38:51Z","timestamp":1782484731588,"version":"3.54.5"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005892","name":"China Academy of Chinese Medical Sciences","doi-asserted-by":"publisher","award":["CI2023C046YLL"],"award-info":[{"award-number":["CI2023C046YLL"]}],"id":[{"id":"10.13039\/501100005892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Atherosclerosis (AS) is a central pathological driver underlying most cardiovascular diseases. Gut microbiota and related metabolites participate in regulating atherosclerosis.\n                      <jats:italic>Panax ginseng<\/jats:italic>\n                      and\n                      <jats:italic>Polygonum cuspidatum<\/jats:italic>\n                      (GP) herb pair has traditionally been used for cardiovascular diseases. Some active compounds in GP have shown anti-atherosclerotic effects and the effects of GP still needs more evidence-based supports. Therefore, this study aims to investigate the potential effects of GP on atherosclerosis and explore the underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Fifty C57BL\/6J ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were randomly assigned to five groups: model, statin, low-dose GP, medium-dose GP and high-dose GP. They were fed a high-fat diet (HFD) to induce atherosclerosis. Ten wild-type C57BL\/6J mice were given chow diet and served as controls. After 12-week intervention, their aortic tissues were collected for Oil Red O staining, colon tissues for Alcian staining and immunofluorescence, and serum samples for measurement of lipid levels and inflammatory cytokines. Then, their fecal DNA was extracted for metagenomic sequencing, while cecum and ileocecal valves were for untargeted metabolomics. Finally, fecal microbiota transplantation was performed to assess the contribution of gut microbiota to observed effects. Twenty additional ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice were randomized to two groups: FMT-Mod and FMT-GPH, given feces from the model or high-dose GP group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Atherosclerotic plaques accumulated in the aorta and aortic sinus after HFD, while statin and high-dose GP alleviated this burden. TC, TG, LDL-C, MCP-1, MCP-3 and IL-2 showed significant increase after HFD, while statin and GP decreased LDL-C, MCP-1 and MCP-3. The goblet cells, ZO-1 and Occludin decreased after HFD, while statin and GP increased them, indicating that the intestinal barrier integrity was improved. Additionally, the composition of gut microbiota was modulated by GP. Some candidate taxa were identified, such as\n                      <jats:italic>Bifidobacteriales<\/jats:italic>\n                      ,\n                      <jats:italic>Bacteroidetes<\/jats:italic>\n                      and\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      . Twenty-two metabolites were differentially abundant among the control, model and GP groups. Nineteen of them were modulated by HFD and reversed by GP, including 1-methylnicotinamide, dopamine and lysoPA (0:0\/18:0). Mice given fecal transplants from the high-dose GP group showed less aortic plaques, lower levels of some lipid and inflammatory cytokines, more goblet cells, more expression of ZO-1 and Occludin, and more 1-methylnicotinamide than those given fecal transplants from the model group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study suggests that GP is beneficial for alleviating atherosclerosis in HFD-induced ApoE\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice, potentially by modulating the composition of gut microbiota and related metabolites.\n                    <\/jats:p>\n                  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