{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:02:21Z","timestamp":1785301341813,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Municipal Natural Science Foundation","award":["L2606073"],"award-info":[{"award-number":["L2606073"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2025-I2M-KJ-016"],"award-info":[{"award-number":["2025-I2M-KJ-016"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["3332025150"],"award-info":[{"award-number":["3332025150"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Glycyrrhizic acid (GL), a natural triterpenoid glycoside extracted from the \u201cmedicine food homology\u201d herb Glycyrrhiza glabra L., exhibits potent anti-atherosclerotic effects; yet its underlying mechanisms remain unclear due to its poor oral bioavailability. The gut microbiota plays a pivotal role in the development of atherosclerosis (AS). In this study, the microbiota-dependent anti-AS effects of GL were evaluated in high-fat diet (HFD)-fed ApoE\u2212\/\u2212 mice using antibiotic depletion and fecal microbiota transplantation (FMT). Integrated metagenomic and metabolomic analyses were performed to identify the key bioactive microbial metabolite. Further in vivo and in vitro experiments, including co-immunoprecipitation and dual-luciferase reporter assays, were utilized to elucidate the underlying molecular mechanisms. It was demonstrated that oral administration of GL alleviated AS in a microbiota-dependent manner by reversing gut dysbiosis, improving intestinal barrier function, and reducing pro-inflammatory lipopolysaccharide (LPS) levels. GL shifted intestinal tryptophan metabolism toward bacterial-derived indole-3-lactic acid (ILA) production, suppressing LPS-induced vascular endothelial adhesion dysfunction by activating the aryl hydrocarbon receptor (AhR). Mechanistically, ILA-activated AhR interacted with the NF-\u03baB subunit p65 in the cytoplasm, effectively preventing the nuclear translocation of p65 and suppressing the promoter activities of adhesion molecules (VCAM1 and ICAM1), resulting in the amelioration of HFD-induced AS. These findings elucidate the microbiota-dependent mechanism of orally administered GL against AS, and highlight the therapeutic potential of targeting the ILA-AhR-p65 axis in the vascular endothelium as a strategy for AS.<\/jats:p>","DOI":"10.3390\/ijms27156694","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:54:26Z","timestamp":1785153266000},"page":"6694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glycyrrhizic Acid Alleviates Atherosclerosis in ApoE\u2212\/\u2212 Mice via Microbial Indole-3-Lactic Acid-Mediated AhR-p65 Interaction in the Endothelium"],"prefix":"10.3390","volume":"27","author":[{"given":"Haoran","family":"Shen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Huang","sequence":"additional","affiliation":[{"name":"Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyu","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitong","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Huang","sequence":"additional","affiliation":[{"name":"Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0073-4357","authenticated-orcid":false,"given":"Yanxing","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiandong","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"},{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20230090","DOI":"10.1002\/EXP.20230090","article-title":"Advances in the treatment of atherosclerosis with ligand-modified nanocarriers","volume":"4","author":"Deng","year":"2024","journal-title":"Exploration"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.cell.2022.04.004","article-title":"Atherosclerosis: Recent developments","volume":"185","author":"Lusis","year":"2022","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Caselli, C., De Caterina, R., Ragusa, R., Liga, R., Gimelli, A., Scholte, A., Clerico, A., Knuuti, J., and Neglia, D. (2021). Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome. Antioxidants, 10.","DOI":"10.3390\/antiox10122002"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1111\/jcmm.14060","article-title":"Exosomes from mesenchymal stem cells expressing miR-125b inhibit neointimal hyperplasia via myosin IE","volume":"23","author":"Wang","year":"2019","journal-title":"J. Cell. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s12933-019-0947-5","article-title":"Luseogliflozin attenuates neointimal hyperplasia after wire injury in high-fat diet-fed mice via inhibition of perivascular adipose tissue remodeling","volume":"18","author":"Mori","year":"2019","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1161\/CIRCULATIONAHA.113.007559","article-title":"Inhibition of glycosphingolipid synthesis ameliorates atherosclerosis and arterial stiffness in apolipoprotein E\u2212\/\u2212 mice and rabbits fed a high-fat and -cholesterol diet","volume":"129","author":"Chatterjee","year":"2014","journal-title":"Circulation"},{"key":"ref_7","first-page":"1006","article-title":"Statin-Associated Muscle Disease: Advances in Diagnosis and Management","volume":"15","author":"Taylor","year":"2018","journal-title":"Neurother. J. Am. Soc. Exp. Neurother."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mooranian, A., Zamani, N., Takechi, R., Luna, G., Mikov, M., Golo\u010dorbin-Kon, S., Elnashar, M., Arfuso, F., and Al-Salami, H. (2019). An in vivo pharmacological study: Variation in tissue-accumulation for the drug probucol as the result of targeted microtechnology and matrix-acrylic acid optimization and stabilization techniques. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0214984"},{"key":"ref_9","first-page":"925","article-title":"Aspirin response and related factors in aged patients","volume":"39","author":"Feng","year":"2011","journal-title":"Zhonghua Xin Xue Guan Bing ZA Zhi"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1161\/CIRCULATIONAHA.118.034645","article-title":"Residual Inflammatory Risk on Treatment With PCSK9 Inhibition and Statin Therapy","volume":"138","author":"Pradhan","year":"2018","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"106157","DOI":"10.1016\/j.phrs.2022.106157","article-title":"Targeting the residual cardiovascular risk by specific anti-inflammatory interventions as a therapeutic strategy in atherosclerosis","volume":"178","author":"Hafiane","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3171","DOI":"10.1093\/cvr\/cvac057","article-title":"Mechanisms, therapeutic implications, and methodological challenges of gut microbiota and cardiovascular diseases: A position paper by the ESC Working Group on Coronary Pathophysiology and Microcirculation","volume":"118","author":"Tousoulis","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e075180","DOI":"10.1136\/bmj-2023-075180","article-title":"Evidence for clinical interventions targeting the gut microbiome in cardiometabolic disease","volume":"383","author":"Ghosh","year":"2023","journal-title":"BMJ"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20240332","DOI":"10.1002\/EXP.20240332","article-title":"Gut Microbiota-Associated Metabolites Affected the Susceptibility to Heart Health Abnormality in Young Migrants at High-Altitude: Gut Microbiota and Associated Metabolites Impart Heart Health in Plateau","volume":"5","author":"Zhou","year":"2025","journal-title":"Exploration"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1161\/CIRCRESAHA.120.316242","article-title":"Gut Microbiota and Cardiovascular Disease","volume":"127","author":"Witkowski","year":"2020","journal-title":"Circ. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Canyelles, M., Borr\u00e0s, C., Rotllan, N., Tondo, M., Escol\u00e0-Gil, J.C., and Blanco-Vaca, F. (2023). Gut Microbiota-Derived TMAO: A Causal Factor Promoting Atherosclerotic Cardiovascular Disease?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031940"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41522-021-00205-8","article-title":"Berberine attenuates choline-induced atherosclerosis by inhibiting trimethylamine and trimethylamine-N-oxide production via manipulating the gut microbiome","volume":"7","author":"Li","year":"2021","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1111\/bph.14933","article-title":"Butyrate protects against high-fat diet-induced atherosclerosis via up-regulating ABCA1 expression in apolipoprotein E-deficiency mice","volume":"177","author":"Du","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/s41392-023-01613-2","article-title":"Gut microbe-derived metabolite indole-3-carboxaldehyde alleviates atherosclerosis","volume":"8","author":"Lu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2413010","DOI":"10.1002\/advs.202413010","article-title":"The Metabolite Indole-3-Acetic Acid of Bacteroides Ovatus Improves Atherosclerosis by Restoring the Polarisation Balance of M1\/M2 Macrophages and Inhibiting Inflammation","volume":"12","author":"Liu","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.vph.2018.03.001","article-title":"Non-coding RNA regulation of endothelial and macrophage functions during atherosclerosis","volume":"114","author":"Aryal","year":"2019","journal-title":"Vasc. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"117487","DOI":"10.1016\/j.cca.2023.117487","article-title":"ICAM-1 and VCAM-1: Gatekeepers in various inflammatory and cardiovascular disorders","volume":"548","author":"Singh","year":"2023","journal-title":"Clin. Chim. Acta"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"114540","DOI":"10.1016\/j.bcp.2021.114540","article-title":"MiR-520b inhibits endothelial activation by targeting NF-\u03baB p65-VCAM1 axis","volume":"188","author":"Yang","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s41577-019-0125-8","article-title":"The aryl hydrocarbon receptor: An environmental sensor integrating immune responses in health and disease","volume":"19","author":"Rothhammer","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41573-025-01172-x","article-title":"The aryl hydrocarbon receptor: A rehabilitated target for therapeutic immune modulation","volume":"24","author":"Polonio","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.1105\/tpc.110.082685","article-title":"Triterpene functional genomics in licorice for identification of CYP72A154 involved in the biosynthesis of glycyrrhizin","volume":"23","author":"Seki","year":"2011","journal-title":"Plant Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"175196","DOI":"10.1016\/j.ejphar.2022.175196","article-title":"Glycyrrhizin ameliorates vascular endothelial cell senescence by inhibiting HMGB1 in HFD\/STZ-induced diabetic rats and human umbilical vein endothelial cells","volume":"931","author":"Liu","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Thakur, V., Alcoreza, N., Delgado, M., Joddar, B., and Chattopadhyay, M. (2021). Cardioprotective Effect of Glycyrrhizin on Myocardial Remodeling in Diabetic Rats. Biomolecules, 11.","DOI":"10.3390\/biom11040569"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tan, D., Tseng, H.H.L., Zhong, Z., Wang, S., Vong, C.T., and Wang, Y. (2022). Glycyrrhizic Acid and Its Derivatives: Promising Candidates for the Management of Type 2 Diabetes Mellitus and Its Complications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231910988"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"755","DOI":"10.3892\/mmr.2021.12395","article-title":"Gycyrrhizic acid alleviates atherosclerotic lesions in rats with diabetes mellitus","volume":"24","author":"Zhao","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e00714","DOI":"10.1002\/prp2.714","article-title":"Protective effect of glycyrrhizin on coronary microembolization-induced myocardial dysfunction in rats","volume":"9","author":"Yuan","year":"2021","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e005790","DOI":"10.1161\/JAHA.117.005790","article-title":"Potent Vasoconstrictor Kisspeptin-10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist","volume":"6","author":"Sato","year":"2017","journal-title":"J. Am. Heart Assoc."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4580","DOI":"10.2174\/1381612820666140522115801","article-title":"Impact of MCP-1 in atherosclerosis","volume":"20","author":"Lin","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6219","DOI":"10.2174\/0929867325666191011115407","article-title":"Advances in Pharmacological Activities and Mechanisms of Glycyrrhizic Acid","volume":"27","author":"Chen","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1159\/000502692","article-title":"Low Dose of Dipotassium Glycyrrhizate Counteracts Atherosclerosis Progression in Apoe\u2212\/\u2212 Female Mice","volume":"56","author":"Palone","year":"2019","journal-title":"J. Vasc. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1161\/CIRCULATIONAHA.123.063914","article-title":"Streptococcus Species Abundance in the Gut Is Linked to Subclinical Coronary Atherosclerosis in 8973 Participants From the SCAPIS Cohort","volume":"148","author":"Dekkers","year":"2023","journal-title":"Circulation"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.gendis.2021.09.007","article-title":"Desulfovibrio desulfuricans aggravates atherosclerosis by enhancing intestinal permeability and endothelial TLR4\/NF-\u03baB pathway in Apoe (\u2212\/\u2212) mice","volume":"10","author":"Zhang","year":"2023","journal-title":"Genes Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1161\/CIRCRESAHA.122.321975","article-title":"Flavonifractor plautii Protects Against Elevated Arterial Stiffness","volume":"132","author":"Luo","year":"2023","journal-title":"Circ. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"137522","DOI":"10.1016\/j.ijbiomac.2024.137522","article-title":"Bacterial cellulose is a desirable biological macromolecule that can prevent obesity via modulating lipid metabolism and gut microbiota","volume":"283","author":"Han","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Grigor\u2019eva, I.N. (2020). Gallstone Disease, Obesity and the Firmicutes\/Bacteroidetes Ratio as a Possible Biomarker of Gut Dysbiosis. J. Pers. Med., 11.","DOI":"10.3390\/jpm11010013"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.cmet.2023.06.004","article-title":"Tryptophan metabolism in health and disease","volume":"35","author":"Xue","year":"2023","journal-title":"Cell Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s40168-023-01606-x","article-title":"High-fat diet-disturbed gut microbiota-colonocyte interactions contribute to dysregulating peripheral tryptophan-kynurenine metabolism","volume":"11","author":"Sun","year":"2023","journal-title":"Microbiome"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease","volume":"9","author":"Roager","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s40168-024-01896-9","article-title":"Bacteroides uniformis degrades \u03b2-glucan to promote Lactobacillus johnsonii improving indole-3-lactic acid levels in alleviating colitis","volume":"12","author":"Zhang","year":"2024","journal-title":"Microbiome"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e2309032120","DOI":"10.1073\/pnas.2309032120","article-title":"Bacterial indole-3-lactic acid affects epithelium-macrophage crosstalk to regulate intestinal homeostasis","volume":"120","author":"Yu","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1186\/s12964-025-02454-y","article-title":"Indole-3-lactic acid protects the gut vascular barrier following intestinal ischemia injury through AhR\/Nrf2\/STAT3 mediated claudin 2 downregulation","volume":"23","author":"Jia","year":"2025","journal-title":"Cell Commun. Signal. CCS"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41392-025-02500-8","article-title":"The aryl hydrocarbon receptor: Structure, signaling, physiology and pathology","volume":"11","author":"Coumoul","year":"2026","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1074\/jbc.M113.505578","article-title":"Cross-talk between aryl hydrocarbon receptor and the inflammatory response: A role for nuclear factor-\u03baB","volume":"289","author":"Vogel","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e70081","DOI":"10.1002\/agt2.70081","article-title":"Supramolecular Assembly of Triterpenoids: Current State and Biomedical Perspectives","volume":"6","author":"Zhong","year":"2025","journal-title":"Aggregate"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117478","DOI":"10.1016\/j.atherosclerosis.2024.117478","article-title":"Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4\/MyD88\/NF-\u03baB signaling pathway","volume":"391","author":"Quan","year":"2024","journal-title":"Atherosclerosis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"119658","DOI":"10.1016\/j.lfs.2021.119658","article-title":"In vitro evaluation of the involvement of Nrf2 in maslinic acid-mediated anti-inflammatory effects in atheroma pathogenesis","volume":"278","author":"Ooi","year":"2021","journal-title":"Life Sci."},{"key":"ref_52","first-page":"157506","article-title":"Panax notoginseng saponin mitigates glycolysis to regulate macrophage polarization and sphingolipid metabolism via hypoxia-inducible factor-1 to alleviate atherosclerosis","volume":"149","author":"Li","year":"2025","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_53","first-page":"157503","article-title":"Ginsenoside Rb1 alleviates atherosclerosis by modulating vascular smooth muscle cell proliferation, foam cell formation, and autophagy","volume":"149","author":"Yuan","year":"2025","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"116158","DOI":"10.1016\/j.jep.2023.116158","article-title":"Microbiota-derived short-chain fatty acids mediate the effects of dengzhan shengmai in ameliorating cerebral ischemia via the gut-brain axis","volume":"306","author":"Guo","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Shen, H., Yu, X., Wang, Z., Zhou, S., Jiang, J., Guo, H., and Han, Y. (2026). Gut Microbiota Remodeling Mediates the Therapeutic Effects of a Plant-Based Medicine on DSS-Induced Ulcerative Colitis in Mice via the Butyrate-SVCT1-Vitamin C Axis. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27052245"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e2412667","DOI":"10.1002\/advs.202412667","article-title":"3-HKA Promotes Vascular Remodeling After Stroke by Modulating the Activation of A1\/A2 Reactive Astrocytes","volume":"12","author":"Chen","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"115916","DOI":"10.1016\/j.biopha.2023.115916","article-title":"Bacterial butyrate mediates the anti-atherosclerotic effect of silybin","volume":"169","author":"Shen","year":"2023","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6694\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:33:14Z","timestamp":1785299594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/15\/6694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":57,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27156694"],"URL":"https:\/\/doi.org\/10.3390\/ijms27156694","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}