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The occurrence of ALI is highly correlated with the out\u2010of\u2010control inflammatory factors. Therefore, inflammatory inhibition is a crucial measure for treating sepsis\u2010induced ALI. Isoferulic acid (IFA) possesses effective anti\u2010inflammatory effects; however, its role in ALI and its molecular mechanisms remain to be further explored. This work focused on analyzing the possible role of IFA in combating sepsis\u2010induced IFA and exploring the associated mechanisms. CLP mice and LPS\u2010induced RAW264.7 cells were employed as the in\u00a0vivo and in\u00a0vitro experimental models. Effects of IFA on inflammation and its mechanisms were assessed using network pharmacology, molecular docking, surface plasmon resonance imaging (SPRi), qRT\u2010PCR, ELISA, immunofluorescence analysis, and Western blot. According to in\u00a0vivo and in\u00a0vitro experimental results, IFA down\u2010regulated inflammatory factors TNF\u2010\u03b1, IL\u20106, and IL\u20101\u03b2 in CLP mice and LPS\u2010exposed RAW264.7 cells. IFA treatment significantly improved the sepsis\u2010induced inflammation and protected lung function. Furthermore, as revealed by network pharmacology analysis, JAK2 was an important target for the interaction between IFA and ALI. Moreover, molecular docking and SPR results demonstrated a close binding between IFA and JAK2. Further research revealed that IFA suppressed JAK2\/STAT3 pathway activation; besides, the therapeutic effect of IFA on ALI was not enhanced by incubation with the JAK2 inhibitor (AG490). Our results offer the preliminary evidence that IFA can restore the impaired function of CLP mice and RAW264.7 cells by alleviating the sepsis\u2010induced inflammation. Additionally, IFA mitigates the sepsis\u2010induced ALI through inhibiting JAK2\/STAT3 pathway activation. Therefore, IFA may potentially be used to treat sepsis\u2010induced lung injury.<\/jats:p>","DOI":"10.1002\/ptr.8526","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T04:49:49Z","timestamp":1749444589000},"page":"3225-3240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Isoferulic Acid Mitigates Acute Lung Injury Induced by Sepsis Through the Inhibition of <scp>JAK2<\/scp>"],"prefix":"10.1002","volume":"39","author":[{"given":"Tong","family":"Xu","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Xu","sequence":"additional","affiliation":[{"name":"The Tenth Affiliated Hospital Southern Medical University (Dongguan People's Hospital)  Dongguan 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