{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T22:29:58Z","timestamp":1779229798631,"version":"3.51.4"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The <jats:italic>HuoXueTongFu<\/jats:italic> Formula (HXTF) originates from the classic prescription \u201c<jats:italic>DaHuangMuDan<\/jats:italic> Decoction\u201d from the \u201cSynopsis of the golden chamber\u201d. Our previous study revealed that HXTF has a positive effect on postoperative peritoneal adhesion (PPA). However, the specific mechanism of HXTF on PPA formation within the time-to-treatment window has not been fully elucidated. This study aimed to determine the critical roles of HXTF as a result of its specific anti-inflammatory and antifibrinolytic activities for PPA treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The eight main bioactive components of HXTF were subjected to high-performance liquid chromatography-mass spectrometry. The core targets, critical biological processes, and underlying pathways of HXTF and PPA were identified via a series of network pharmacological methods. The specific anti-inflammatory function in the initial step of PPA formation was validated in peritoneal macrophages (PMs) isolated from PPA mice on Day 3 postsurgery. The potential anti-fibrinolytic activity in the next stage of PPA formation was subsequently explored in PPA mice on Day 7 postsurgery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Network pharmacology revealed 160 common targets between HXTF and PPA. Several core targets, i.e., matrix metalloproteinase 9 (MMP9), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor 1 (PAI-1), were annotated as important biological processes (extracellular matrix disassembly and the collagen catabolic process). Validation experiments revealed that HXTF could induce macrophage polarization-mediated anti-inflammatory reactions by increasing the phagocytic capacity of PMs and promoting the release of anti-inflammatory cytokines (IL-4 and IL-10). In addition, HXTF promoted fibrinogenolysis and improved fibrinolytic activity, thereby inhibiting collagen deposition and reducing adhesion development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The ameliorative effects of herbal HXTF on PPA formation are attributable to the induction of macrophage polarization-mediated anti-inflammatory reactions in the early stage of PPA formation and the promotion of fibrinogenolysis and fibrinolytic activity in the middle stage of PPA formation. HXTF may be a promising alternative agent for the prevention and treatment of PPA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1510766","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T06:56:29Z","timestamp":1737615389000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Herbal HuoXueTongFu Formula with anti-inflammatory and fibrinolytic activity regulation for the prevention of postoperative peritoneal 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