{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:01:03Z","timestamp":1791198063623,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"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":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>To investigate the effects and targets of cordycepin (COR) in alleviating non\u2010alcoholic fatty liver disease (NAFLD). High\u2010fat diet was used to induce NAFLD in mice, and after COR gavage administration, changes in liver function, glucose and lipid metabolism, and ferroptosis\u2010related signaling were detected. In\u00a0vitro, palmitic acid (PA) and oleic acid (PSA) were combined to induce hepatocyte lipid injury. The effect of COR on hepatocyte ferroptosis was examined. GCH1 conditional knockout mice (GCH1\u2010CKO) and hepatocyte models were constructed, and AAV9\u2010GCH1 was used to construct GCH1 overexpression mouse models to verify the effect of GCH1 on NAFLD. CETSA\u2010WB, co\u2010immunoprecipitation, and DARTS were employed in the COR\u2010GCH1 interaction and mechanism studies to validate the targeted binding relationship between COR and GCH1. Animal\u2010level studies showed that COR could improve glucose and lipid metabolism and liver function damage in mouse NAFLD, inhibit ferroptosis occurrence and lipid peroxidation injury. Cell\u2010level results showed that COR could inhibit hepatocyte ferroptosis. The ferroptosis\u2010inhibiting effect of GCH1 is independent of GPX4 and other signals; GCH1 directly inhibits reactive oxygen free radicals and suppresses lipid metabolism peroxidation damage. COR's effects are not related to classical anti\u2010ferroptosis signals such as GPX4 and Nrf2, but only related to GCH1. COR can target the GCH1 K155 site, stabilize protein levels by inhibiting GCH1 ubiquitination degradation, and when GCH1 is knocked out, COR's effects are antagonized. GCH1 has a protective role in NAFLD, and this effect is independent of classical GPX4 signaling. COR can target the GCH1 K155 site, inhibit GCH1 ubiquitination thereby preventing protein degradation and exerting protein stabilization. COR elevates GCH1 levels to inhibit ferroptosis. COR is a small molecule with potential for treating NAFLD.<\/jats:p>","DOI":"10.1002\/ptr.70424","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T14:18:17Z","timestamp":1786025897000},"page":"5886-5900","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cordycepin Alleviates Non Alcoholic Fatty Liver Disease Progression by Stabilizing\n                    <scp>GCH1<\/scp>\n                    to Inhibit Ferroptosis"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-580X","authenticated-orcid":false,"given":"Chenyang","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of Jiaxing University  Jiaxing Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Urology The Second Affiliated Hospital of Jiaxing University  Jiaxing Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyan","family":"Pei","sequence":"additional","affiliation":[{"name":"College of Chinese Medicinal Materials, Jilin Agricultural University  Changchun Jilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of Jiaxing University  Jiaxing Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of Jiaxing University  Jiaxing Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2519-5217","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy 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