{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T18:10:36Z","timestamp":1781719836745,"version":"3.54.5"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"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>Liver fibrosis, driven by excessive extracellular matrix (ECM) deposition and activation of hepatic stellate cells (HSCs), still lacks effective therapies, partly due to the absence of human-relevant models. Lycii Radicis Cortex (LRC), a traditional Chinese medicine, exhibits reported anti-inflammatory and antioxidant activities, yet its anti-fibrotic potential has not been validated in human organoid-based systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established hiPSC-derived multilineage hepatobiliary organoids (mHBOs) containing mesoderm-derived HSCs and implemented a TGF-\u03b2\u2013induced fibrosis model within this platform. Using mHBOs alongside a CCl4-injury mouse model, we assessed the anti-fibrotic activity of LRC, and investigated underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      LRC significantly attenuated fibrosis in mHBOs and in CCl\n                      <jats:sub>4<\/jats:sub>\n                      -injured mice, reducing ECM accumulation and HSC activation. In mHBOs, LRC activated the cAMP\u2013PKA\u2013CREB pathway, thereby suppressing HSC activation and reducing parenchymal apoptosis; these effects were reversed by PKA inhibition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LRC exhibits potent anti-fibrotic activity in a physiologically relevant human organoid model, providing mechanistic insight into HSC regulation and supporting its potential as a candidate therapy for chronic liver disease. Furthermore, this study introduces a translational platform integrating animal models and hiPSC-derived organoids to facilitate anti-fibrotic drug discovery and evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1730255","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T14:23:45Z","timestamp":1764080625000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Lycii radicis cortex alleviates fibrosis in hiPSC-derived multilineage hepatic organoids via the cAMP-PKA pathway"],"prefix":"10.3389","volume":"16","author":[{"given":"Junming","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopu","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfei","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiasen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanbin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jicai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoni","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianjie","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenfang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.stemcr.2019.08.007","article-title":"Robust, long-term culture of endoderm-derived hepatic organoids for disease modeling","volume":"13","author":"Akbari","year":"2019","journal-title":"Stem cell Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"7873","DOI":"10.3390\/ijms25147873","article-title":"Liver fibrosis: from basic science towards clinical progress, focusing on the central role of hepatic stellate cells","volume":"25","author":"Akk\u0131z","year":"2024","journal-title":"Int. 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