{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:07:25Z","timestamp":1789106845466,"version":"build-2803163510"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"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>Background<\/jats:title>\n                    <jats:p>\n                      Rhabdomyolysis (RM) is a potentially life-threatening syndrome characterized by skeletal muscle damage, with acute kidney injury (AKI) being its most severe complication. Currently, no effective treatment exists for RM-induced AKI. Crocins, the major bioactive constituents extracted from the stigma of\n                      <jats:italic>Crocus sativus<\/jats:italic>\n                      L. (Saffron), possess diverse pharmacological activities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to explore the pharmacological effect and possible mechanism of crocins in the treatment of RM-induced AKI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Network analysis was first applied to predict potential targets of crocins against RM. A rat model of hypertonic glycerol-induced RM was then established to evaluate pharmacological effect, including assessment of muscle and renal pathology, inflammatory cytokines, biochemical markers, and oxidative stress-related enzymes. Tandem mass tag\u2013based quantitative proteomics was further employed to identify key disease targets. Molecular docking was then conducted to validate potential target interactions of crocins in RM-induced AKI treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Animal experiments demonstrated that crocins alleviated muscle and renal injuries by inhibiting inflammation and oxidative stress while preserving hepatic and renal functions. Proteomic analysis identified perilipin 1 (PLIN1) as a critical candidate biomarker mediating these effects. Both network analysis and proteomics indicated that the peroxisome proliferator-activated receptors (PPARs) signaling pathway was closely involved in protective mechanism. Furthermore, Western blotting confirmed that crocins exerted pharmacological effect through regulating the PLIN1\/PPARs signaling pathway. Molecular docking revealed that the best docking activities were demonstrated by crocin I\/II\u2013PLIN1, crocin I\u2013PPAR\u03b1, and crocin II\u2013PPAR\u03b3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Crocins mitigated RM-induced AKI primarily by suppressing inflammation and oxidative stress via the PLIN1\/PPARs signaling pathway. These findings provide a scientific and theoretical basis for the potential clinical application of crocins in treating RM-induced AKI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1874817","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:29:23Z","timestamp":1789104563000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Crocins ameliorate acute kidney injury in glycerol-induced rhabdomyolysis by targeting the PLIN1\/PPARs signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Fangbo","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqing","family":"Cai","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huamin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Basic Theory of Chinese Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongjun","family":"Yang","sequence":"additional","affiliation":[{"name":"China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"116387","DOI":"10.1016\/j.taap.2023.116387","article-title":"Pentoxifylline and thiamine ameliorate rhabdomyolysis-induced acute kidney injury in rats via suppressing TLR4\/NF-kappaB and NLRP-3\/caspase-1\/gasdermin mediated-pyroptosis","volume":"461","author":"Al-Kharashi","year":"2023","journal-title":"Toxicol. 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