{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:03:57Z","timestamp":1792004637128,"version":"4.4.0"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Shandong Province Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2023QC033"],"award-info":[{"award-number":["ZR2023QC033"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007129","name":"Shandong Province Natural Science Foundation","doi-asserted-by":"crossref","award":["ZR2024QC115"],"award-info":[{"award-number":["ZR2024QC115"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008992","name":"Yantai University","doi-asserted-by":"crossref","award":["SM22B197"],"award-info":[{"award-number":["SM22B197"]}],"id":[{"id":"10.13039\/100008992","id-type":"DOI","asserted-by":"crossref"}]},{"award":["SM22B197"],"award-info":[{"award-number":["SM22B197"]}],"id":[{"id":"https:\/\/ror.org\/01rp41m56","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Graduate Innovation Foundation of Yantai University","award":["GGIFYTU2530"],"award-info":[{"award-number":["GGIFYTU2530"]}]},{"award":["GGIFYTU2530"],"award-info":[{"award-number":["GGIFYTU2530"]}],"id":[{"id":"https:\/\/ror.org\/01rp41m56","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>The global rise in metabolic disorders demands novel interventions targeting starch digestion. This study investigated two dietary phenolic acids (caffeic acid (CA) and p-hydroxycinnamic acid (p-HA)) as inhibitors of \u03b1-amylase and \u03b1-glucosidase through integrated experimental and computational approaches. Molecular docking showed distinct binding modes, and CA formed stable hydrogen bonds with catalytic residues of \u03b1-glucosidase, while p-HA interacted mainly with \u03b1-amylase via hydrophobic contacts. Enzyme kinetics revealed concentration-dependent mixed-type inhibition, with CA being more potent against \u03b1-glucosidase and p-HA against \u03b1-amylase. Spectroscopic analysis indicated both acids induced structural changes in the enzymes, with CA causing greater \u03b1-helix reduction (\u03947.03% vs. \u03942.10%) by altering the tryptophan microenvironment. Moreover, both compounds significantly suppress glucose absorption in the proximal small intestine in an ex vivo everted gut sac model, with p-HA exhibiting exceptional efficacy in the duodenum. These findings clarify structure\u2013activity relationships and support the potential use of CA and p-HA as local intestinal agents for modulating carbohydrate absorption.<\/jats:p>","DOI":"10.3390\/foods15111972","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"1972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular Basis for the Divergent Inhibition of \u03b1-Amylase and \u03b1-Glucosidase by Phenolic Acids: The Critical Role of Hydroxyl Substitution"],"prefix":"10.3390","volume":"15","author":[{"given":"Shuang","family":"Yang","sequence":"first","affiliation":[{"name":"School of Food Engineering, Ludong University, Yantai 264025, China"},{"name":"Center for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4092-5912","authenticated-orcid":false,"given":"Yongxing","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyu","family":"Han","sequence":"additional","affiliation":[{"name":"Center for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Cao","sequence":"additional","affiliation":[{"name":"Center for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Hu","sequence":"additional","affiliation":[{"name":"Center for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6702-6286","authenticated-orcid":false,"given":"Mei","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Feng","sequence":"additional","affiliation":[{"name":"Center for Mitochondria and Healthy Aging, College of Life Sciences, Yantai University, Yantai 264005, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinfang","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Food Engineering, Ludong University, Yantai 264025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113471","DOI":"10.1016\/j.foodres.2023.113471","article-title":"Peanut skin procyanidins reduce intestinal glucose transport protein expression, regulate serum metabolites and ameliorate hyperglycemia in diabetic mice","volume":"173","author":"Liu","year":"2023","journal-title":"Food Res. 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