{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:53:09Z","timestamp":1789570389378,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070584"],"award-info":[{"award-number":["82070584"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20519"],"award-info":[{"award-number":["U23A20519"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Aberrant activation of the cGAS\u2010STING pathway has been implicated in the pathogenesis of diverse inflammatory diseases. Kurarinone, a flavonoid compound isolated from Sophorae tonkinensis Radix et Rhizoma, has been reported to exhibit anti\u2010inflammatory effects and is used to treat inflammatory diseases. But the effect of kurarinone on the cGAS\u2010STING pathway has not been well studied. We aimed to investigate the impact of Kurarinone on cGAS\u2010STING pathway activation and its protective effect against cGAS\u2010STING\u2010mediated inflammatory diseases. BMDMs and THP\u20101 cells pretreated with Kurarinone or vehicle were stimulated with ISD or various STING agonists; the protein level of p\u2010IRF3 was analyzed by western blotting, and the secretion and mRNA level of inflammatory cytokines were detected by ELISA and qPCR, respectively. To further explore the potential targets and molecular mechanisms of Kurarinone, nucleocytoplasmic separation assays, STING oligomerization experiments, cellular thermal shift assays, drug affinity responsive target stability assays, and molecular docking were conducted. Additionally, DSS\u2010induced inflammatory bowel disease and ConA\u2010induced autoimmune hepatitis models were used to evaluate the effects of Kurarinone on cGAS\u2010STING\u2010mediated inflammatory diseases. In\u00a0vitro, Kurarinone inhibited the phosphorylation of STING and IRF3, reduced IFN\u03b2 release, and downregulated the transcription of IFN\u03b2, IL\u20101\u03b2, CXCL10, IL\u20106, TNF\u2010\u03b1, and ISG15, in ISD\u2010stimulated BMDMs and THP\u20101 cells. Additionally, Kurarinone suppressed IRF3 nuclear translocation, disrupted the interaction between STING and IRF3, but did not affect STING oligomerization. Furthermore, Kurarinone reduced the thermostability of STING while increasing its susceptibility to proteolytic degradation. The molecular docking results indicated a strong interaction between Kurarinone and STING. In\u00a0vivo, Kurarinone attenuated the inflammatory response in DSS\u2010induced inflammatory bowel disease and ConA\u2010induced autoimmune hepatitis models by inhibiting cGAS\u2010STING signaling activation. In conclusion, Kurarinone targets the STING protein to interfere with the interaction between IRF3 and STING, thereby inhibiting the activation of the cGAS\u2010STING signaling pathway. Additionally, Kurarinone ameliorates inflammatory diseases by suppressing the cGAS\u2010STING pathway. This study provides a potential candidate drug for the clinical treatment of STING\u2010driven inflammatory diseases.<\/jats:p>","DOI":"10.1002\/ptr.70023","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T23:44:21Z","timestamp":1751499861000},"page":"3450-3465","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Kurarinone Alleviates\n                    <scp>cGAS<\/scp>\n                    \u2010\n                    <scp>STING<\/scp>\n                    \u2010Triggered Inflammatory Diseases by Targeting\n                    <scp>STING<\/scp>"],"prefix":"10.1002","volume":"39","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"School of Pharmacy Chengdu University of Traditional Chinese Medicine  Chengdu China"},{"name":"Department of Hepatology Fifth Medical Center of Chinese PLA General Hospital  Beijing China"},{"name":"Military Institute of 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