{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:04:33Z","timestamp":1790805873742,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether Gastrodin (Gas) attenuates doxorubicin (Dox)-induced cardiomyocyte senescence and apoptosis by regulating the AMPK\/mTOR\/4EBP1 signaling pathway and autophagy-related processes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A Dox-induced senescence model was established in H9c2 cardiomyocytes, and different concentrations of Gas (0.5\u00a0mM and 1\u00a0mM) were used for intervention. Senescence phenotypes were evaluated using SA-\u03b2-gal staining and senescence-associated proteins (P16, P21, and P53). Furthermore, the autophagy inhibitor 3-MA and the AMPK inhibitor Compound C (CC) were applied. Combined with Western blotting, Annexin V\/PI flow cytometry, and immunofluorescence techniques, the expression levels of senescence-related proteins, autophagy-related markers (LC3-II\/I, Beclin-1, and p62), and the phosphorylation levels of key proteins in the AMPK\/mTOR\/4EBP1 signaling pathway were analyzed to explore the potential mechanism of Gas.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with the Dox model group, Gas intervention dose-dependently reduced the percentage of SA-\u03b2-gal-positive cells, downregulated the protein expression levels of P16, P21, P53, and \u03b3-H2AX, and significantly inhibited apoptosis. Mechanistically, Gas treatment partially ameliorated the abnormalities in autophagy-related markers induced by Dox, as evidenced by increased expression of LC3 and Beclin-1 and decreased accumulation of p62, and this ameliorative effect was partially attenuated by 3-MA. Further signaling pathway analysis demonstrated that Gas significantly increased the p-AMPK\/AMPK ratio while decreasing the p-mTOR\/mTOR and p-4EBP1\/4EBP1 ratios. After AMPK inhibition with CC, the activation effect of Gas on autophagy and its protective effects against senescence and apoptosis were both attenuated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings indicate that Gas alleviates Dox-induced cardiomyocyte senescence and apoptosis, and its protective effects may be associated with regulation of the AMPK\/mTOR\/4EBP1 signaling pathway and improvement of autophagy-related processes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1851573","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:29:34Z","timestamp":1781584174000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Gastrodin alleviates cardiomyocyte senescence by regulating autophagy through the AMPK\/mTOR\/4EBP1 pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Mingyue","family":"Yao","sequence":"first","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunqian","family":"Huang","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Song","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhao","family":"Jia","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baihui","family":"Yao","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Li","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]},{"name":"The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou City, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Dong","sequence":"additional","affiliation":[{"name":"The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University","place":["Luzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1161\/circresaha.118.312208","article-title":"Autophagy in cardiovascular aging","volume":"123","author":"Abdellatif","year":"2018","journal-title":"Circ. 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