{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:01:03Z","timestamp":1771930863132,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"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                      Alport syndrome (AS) is a progressive hereditary nephropathy caused by mutations in collagen IV genes, notably COL4A5, leading to proteinuria and kidney failure. Current therapies using RAAS inhibitors show limited efficacy. Triptolide, the main active component of\n                      <jats:italic>Tripterygium wilfordii<\/jats:italic>\n                      , exhibits anti-proteinuric effects but is limited by poor solubility and toxicity. Minnelide, its water-soluble prodrug, provides a promising alternative.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigated the therapeutic potential and mechanisms of Minnelide in a female Col4a5 (X + X-) Alport syndrome mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Mice were treated with Minnelide or vehicle for 3\u00a0months.\n                      <jats:italic>In vitro<\/jats:italic>\n                      ,\n                      <jats:italic>Col4a5<\/jats:italic>\n                      +\/\u2212 podocytes were treated with triptolide, with or without Col4a5 siRNA knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Minnelide significantly reduced proteinuria by 64.2%, improved glomerular pathology, upregulated renal Col4a5 expression, and suppressed endoplasmic reticulum (ER) stress. In podocytes, triptolide increased Col4a5 and alleviated ER stress. Col4a5 knockdown directly induced ER stress, which was reversed by triptolide treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Minnelide demonstrates potent renoprotective effects in AS by upregulating Col4a5 expression and mitigating podocyte ER stress, positioning it as a novel therapeutic candidate.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1761502","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T09:01:13Z","timestamp":1770627673000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Minnelide ameliorates Col4a5+\/\u2212 mice by upregulating Col4a5 and alleviating endoplasmic reticulum stress"],"prefix":"10.3389","volume":"17","author":[{"given":"Bao-wei","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Nephrology, Children\u2019s Hospital of Fudan University, National Children\u2019s Medical Center","place":["Shanghai, China"]},{"name":"Shanghai Kidney Development & Pediatric Kidney Disease Research Center","place":["Shanghai, China"]},{"name":"National Key Laboratory of Kidney Diseases","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Collaborative Innovation Center of Genetics and Development, Institute of Developmental Biology and Molecular Medicine, School of Life Sciences, Fudan 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