{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T05:16:57Z","timestamp":1777526217975,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100004761","name":"the Natural Science Foundation of Hunan Province","doi-asserted-by":"crossref","award":["No. BK20211297"],"award-info":[{"award-number":["No. BK20211297"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["ASSAY and Drug Development Technologies"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:p>\n                    Huxinkang tablets (HXKT) is the formula prescription of Traditional Chinese Medicine for treating atherosclerosis (AS), but its underlying mechanisms remain unclear. Network pharmacology and experimental verification were integrated to explore the therapeutic effects and key targets of HXKT in macrophage-associated genes in vulnerable AS plaques. Our findings indicated that a total of 75 candidate targets of HXKT against vulnerable AS were acquired. Furthermore, five core targets were identified including STAT3, HIF1A, EGFR, ESR1, and BCL2. KEGG pathway analysis demonstrated that these targets participated in the advanced glycation end product \u2013 receptor for advanced glycation end-product (AGE-RAGE) signaling pathway associated with diabetic complications, lipid metabolism, AS, and human cytomegalovirus infection. Molecular docking results indicated that the ESR1-miltirone complex exhibited the highest binding affinity.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    experiments demonstrated that HXKT inhibited oxidized low-density lipoprotein-induced macrophage injury, reversed abnormal expression of key targets, and reduced inflammation and lipid accumulation. Overexpression of STAT3 partially attenuated the protective effects of HXKT, confirming its role as a critical target while underscoring the multi-target mechanism of HXKT. In conclusion, HXKT stabilizes vulnerable atherosclerotic plaques by regulating macrophage function through a multi-component, multi-target mechanism, with STAT3 signaling playing a pivotal role.\n                  <\/jats:p>","DOI":"10.1177\/1540658x251404889","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:28:16Z","timestamp":1768368496000},"page":"216-227","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Network Pharmacology Combined with Experimental Validation to Investigate the Mechanism of Huxinkang Tablets in Treating Atherosclerosis by Modulating Macrophages"],"prefix":"10.1177","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9309-5030","authenticated-orcid":false,"given":"Zhengke","family":"Yu","sequence":"first","affiliation":[{"name":"The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guobing","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaili","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojing","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Zhao","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihong","family":"Chen","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Hunan Academy of Chinese Medicine, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2022.06.018"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307611"},{"issue":"04","key":"e_1_3_2_4_2","first-page":"6","article-title":"Clinical effect of Huxinkang tablets in treatment of microvascular angina with anxiety and depression: An analysis of 32 cases","volume":"38","author":"Ouyang L","year":"2022","unstructured":"Ouyang L, , Yu ZK. Clinical effect of Huxinkang tablets in treatment of microvascular angina with anxiety and depression: An analysis of 32 cases. Hunan J Traditional Chinese Medicine, 2022; 38(04):6\u20138. +13.","journal-title":"Hunan J Traditional Chinese Medicine"},{"issue":"06","key":"e_1_3_2_5_2","first-page":"10","article-title":"Clinical effect of Huxinkang tablets combined with acupuncture in treatment of unstable angina with syndrome of intermingled phlegm and blood stasis: An analysis of 45 cases","volume":"39","author":"Zhu XJ","year":"2023","unstructured":"Zhu XJ, , Wang JS, , Yan X, et al. Clinical effect of Huxinkang tablets combined with acupuncture in treatment of unstable angina with syndrome of intermingled phlegm and blood stasis: An analysis of 45 cases. Hunan J Traditional Chinese Medicine, 2023; 39(06):10\u201313. +22.","journal-title":"Hunan J Traditional Chinese Medicine"},{"issue":"06","key":"e_1_3_2_6_2","first-page":"963","article-title":"Effect of Huxinkang Tablets on atherosclerotic plaque in ApoE-\/-mice based on VEGF\/VEGFR-2 signaling pathway","volume":"32","author":"Yuan H","year":"2023","unstructured":"Yuan H, , Huang CR, , Yu ZK, et al. Effect of Huxinkang Tablets on atherosclerotic plaque in ApoE-\/-mice based on VEGF\/VEGFR-2 signaling pathway. J Emergency in Traditional Chinese Medicine, 2023; 32(06):963\u2013968.","journal-title":"J Emergency in Traditional Chinese Medicine"},{"issue":"02","key":"e_1_3_2_7_2","first-page":"122","article-title":"Effect of Huxinkang on Wnt5a in TLR4 gene knockout mice atherosclerosis model","volume":"18","author":"Dong XF","year":"2019","unstructured":"Dong XF, , Ding XY, , He JX, et al. Effect of Huxinkang on Wnt5a in TLR4 gene knockout mice atherosclerosis model. J Clinical and Experimental Medicine, 2019; 18(02):122\u2013125.","journal-title":"J Clinical and Experimental Medicine"},{"issue":"07","key":"e_1_3_2_8_2","first-page":"854","article-title":"Intervention mechanism of cardiac protection tablets on autophagy in atherosclerotic mice","volume":"44","author":"Huang CR","year":"2023","unstructured":"Huang CR, , Li WS, , Yuan H, et al. Intervention mechanism of cardiac protection tablets on autophagy in atherosclerotic mice. Shaanxi J Traditional Chinese Medicine, 2023; 44(07):854\u2013858.","journal-title":"Shaanxi J Traditional Chinese Medicine"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01840-1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-023-01023-z"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.324086"},{"key":"e_1_3_2_12_2","volume-title":"Effect of Huxinkang on mTOR and Akt of Macrophages Stimulated by Ox-LDL [Master]","author":"X H","year":"2021","unstructured":"X H. Effect of Huxinkang on mTOR and Akt of Macrophages Stimulated by Ox-LDL [Master]. Hunan University of Traditional Chinese Medicine; 2021."},{"key":"e_1_3_2_13_2","volume-title":"Effect of Huxinkang on Ox-LDL Stimulated Macrophage Beclin1, LC3\u2161 [Master]","author":"YuJiao Z","year":"2020","unstructured":"YuJiao Z. Effect of Huxinkang on Ox-LDL Stimulated Macrophage Beclin1, LC3\u2161 [Master]. Hunan University of Traditional Chinese Medicine; 2020."},{"issue":"04","key":"e_1_3_2_14_2","first-page":"153","article-title":"A correlation analysis of chromatographic peaks of Huxinkang tablets and its components based on multi-wavelength high-performance liquid chromatography fingerprints","volume":"35","author":"Yuan QZ","year":"2019","unstructured":"Yuan QZ, , Zhu XJ, , Xi Q, et al. A correlation analysis of chromatographic peaks of Huxinkang tablets and its components based on multi-wavelength high-performance liquid chromatography fingerprints. Hunan J Traditional Chinese Medicine, 2019; 35(04):153\u2013156.","journal-title":"Hunan J Traditional Chinese Medicine"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109375"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1490387"},{"issue":"11","key":"e_1_3_2_17_2","first-page":"159","article-title":"Effect of Huxinkang on ferroptosis and apoptosis of H9C2 cardiomyocytes induced by hypoxia\/reoxygenation","volume":"40","author":"He X","year":"2024","unstructured":"He X, , Chang JY, , Xiaojing Z, et al. Effect of Huxinkang on ferroptosis and apoptosis of H9C2 cardiomyocytes induced by hypoxia\/reoxygenation. Hunan J Traditional Chinese Medicine, 2024; 40(11):159\u2013164.","journal-title":"Hunan J Traditional Chinese Medicine"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109729"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25147755"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.11.016"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-024-03774-6"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.173874"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179724"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.31083\/j.fbl2712329"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36614-w"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107289"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.313290"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.311994"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309927"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.109825"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9RA00705A"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1062229"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2025.106848"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-020-01749-z"}],"container-title":["ASSAY and Drug Development Technologies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1540658X251404889","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1540658X251404889","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1540658X251404889","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:29:00Z","timestamp":1777393740000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1540658X251404889"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,13]]},"references-count":33,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,4,1]]}},"alternative-id":["10.1177\/1540658X251404889"],"URL":"https:\/\/doi.org\/10.1177\/1540658x251404889","relation":{},"ISSN":["1540-658X","1557-8127"],"issn-type":[{"value":"1540-658X","type":"print"},{"value":"1557-8127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,13]]}}}