{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T02:14:15Z","timestamp":1780712055096,"version":"3.54.1"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:00:00Z","timestamp":1768521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["CSTB2023NSCQ-LZX0046"],"award-info":[{"award-number":["CSTB2023NSCQ-LZX0046"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Diabetes mellitus involves complex pathogenesis requiring multi-target interventions.\n                      <jats:italic>Citrus reticulata<\/jats:italic>\n                      \u2018Dahongpao\u2019 from Chongqing exhibits anti-diabetic potential, but its mechanisms remain elusive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We employed an integrative strategy: GC-MS identified 82 compounds (96.61% coverage), dominated by\n                      <jats:italic>D<\/jats:italic>\n                      -limonene (62.48%). Network pharmacology revealed 36 diabetes-related targets. Molecular docking prioritized ligands (thymol: \u22126.8 kcal\/mol with FABP1; n-hexadecanoic acid: \u22126.7 kcal\/mol with PTGS2). Critical validation was achieved via 100-ns molecular dynamics (MD) simulations and MM-GBSA binding free energy calculations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MD simulations demonstrated structural stability (RMSD\u2009&lt;\u20092.5 \u00c5) for core complexes (e.g., CYP19A1\/thymol). MM-GBSA quantified robust binding for FABP1\/dodecanoic acid (\u221243.26 kcal\/mol) and PTGS2\/n-hexadecanoic acid (\u221243.93 kcal\/mol), driven by van der Waals forces. Hydrogen bond dynamics revealed persistent interactions (e.g., thymol\u2013THR102 in FABP1), while RMSF highlighted ligand-induced flexibility in fatty acids. Pathway analysis implicated PPAR signaling and insulin resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Citrus reticulata<\/jats:italic>\n                      \u2018Dahongpao\u2019 essential oil combats diabetes through synergistic multi-target modulation, validated by dynamic ligand\u2013protein stability and energetics. This study presents an in silico framework that integrates phytochemical profiling and computational analyses to facilitate natural product drug discovery.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0338723","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:36:05Z","timestamp":1768588565000},"page":"e0338723","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Integrative GC-MS, network pharmacology, and molecular dynamics elucidate synergistic anti-diabetic mechanisms of Chongqing Citrus reticulata \u2018Dahongpao\u2019 volatile oil via multi-target stabilization"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7926-1017","authenticated-orcid":true,"given":"Wanting","family":"Zhong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YaYi","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujaat","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3419-9340","authenticated-orcid":true,"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"key":"pone.0338723.ref001","doi-asserted-by":"crossref","unstructured":"Association AD. 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