{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T05:04:33Z","timestamp":1780031073030,"version":"3.53.1"},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":147,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes Research"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>According to traditional Chinese medical (TCM) principles diabetic retinopathy (DR) is categorized as a type of \u201cWasting\u2010Thirst Eye Disease.\u201d According to TCM, the pathophysiology of DR is primarily attributed to blood stasis, obstructed collaterals, and concurrent Qi and Yin deficiencies. Yiqi\u2010Tongluo\u2010Huoxue\u2010Mingmu Formula (YQMM), a TCM commonly prescribed for DR, has yet to have its active components and underlying molecular mechanisms fully elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The therapeutic efficacy of YQMM was assessed in mice with diabetes induced by streptozotocin (STZ). The chemical profiles of YQMM and its absorbed prototype components in vivo were characterized using LC\u2010Q\u2010TOF\/MS. After predicting potential targets and pathways using network pharmacology methods and molecular docking, this study validated these computational results through RT\u2010qPCR experiments. To further evaluate the antiproliferative and antiangiogenic effects of YQMM and its active components, HUVECs cultured under high\u2010glucose conditions were used.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The retinal protective effects of YQMM were observed without significant alterations in systemic blood glucose levels. Chemical analysis identified 142 compounds, with five prototype constituents (caffeic acid, isoferulic acid, daidzin, daidzein, and mirificin) detected in plasma. Network pharmacology indicated 118 shared targets between YQMM and DR, with key nodes including TP53, ESR1, JUN, STAT3, and MAPK1, primarily linked to the AGE\u2010RAGE, PI3K\u2010Akt, and HIF\u20101 signaling pathways. Molecular docking predictions revealed strong binding affinities between the targets and the compounds, particularly for daidzin. Both in vivo and in vitro experiments confirmed that YQMM and its active components downregulated the expression of core targets and inhibited high glucose\u2010induced endothelial cell proliferation and tube formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>YQMM confers its protective benefits against DR via a complex interplay of multiple active ingredients acting on diverse molecular targets and signaling networks. These findings elucidate the chemical and mechanistic basis for the clinical efficacy of YQMM, supporting its further development as a promising therapeutic agent for DR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/jdr\/8484553","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:44:48Z","timestamp":1780029888000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Integrated Approach Combining Chemical Profiling, Network Pharmacology, and Experimental Validation Is Used to Clarify the Pharmacological Basis of the Yiqi\u2010Tongluo\u2010Huoxue\u2010Mingmu Formula in Diabetic Retinopathy"],"prefix":"10.1155","volume":"2026","author":[{"given":"Yuan","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Lyu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-6212","authenticated-orcid":false,"given":"Zhu-jun","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2017.03.024"},{"key":"e_1_2_10_2_2","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.diabet.2019.04.002","article-title":"Diabetic Retinopathy, a Vascular and Inflammatory Disease: Therapeutic Implications [J]","volume":"45","author":"Semeraro F.","year":"2019","journal-title":"Diabetes and Metabolism"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-020-00451-4"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2024.07.001"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19061816"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2024.2369292"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109564"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043591"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.977971"},{"key":"e_1_2_10_10_2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s11655-009-0384-5","article-title":"Effect of Qiming Granule on Retinal Blood Circulation of Diabetic Retinopathy: A Multicenter Clinical trial","volume":"15","author":"Luo X.","year":"2009","journal-title":"Chinese Journal of Integrative Medicine"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2014.01.008"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v14.i9.1422"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/578165"},{"key":"e_1_2_10_14_2","first-page":"1815","article-title":"The Effect of Puerarin Against IL-1\u03b2-Mediated Leukostasis and Apoptosis in Retinal Capillary Endothelial Cells (TR-iBRB2)","volume":"20","author":"Zhu X.","year":"2014","journal-title":"Molecular Vision"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156874"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.115861"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00123"},{"key":"e_1_2_10_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.1c01183"},{"key":"e_1_2_10_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027385"},{"key":"e_1_2_10_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.759421"},{"key":"e_1_2_10_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/md18110545"},{"key":"e_1_2_10_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105989"},{"key":"e_1_2_10_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2023.105862"},{"key":"e_1_2_10_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111332"},{"key":"e_1_2_10_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-00939-9"},{"key":"e_1_2_10_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.07.030"},{"key":"e_1_2_10_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40123-022-00581-0"},{"key":"e_1_2_10_28_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202257"},{"key":"e_1_2_10_29_2","first-page":"187","article-title":"Research Progress on the Mechanism of Estrogen in Diabetes Retinopathy[J\/OL]","volume":"14","author":"Wang Z. 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