Data Sheet 1_Compound phellodendron decoction promotes post-fistulotomy wound healing by downregulating neutrophil extracellular traps formation: evidence from a randomized trial and mechanistic studies.docx

While the traditional formula Compound Phellodendron Decoction (CPD) is clinically effective in sitz-bath therapy, its mechanism of action, particularly concerning the novel therapeutic target NETosis, remains unknown. We hypothesized that CPD accelerates healing by downregulating NET formation.</p>Methods<p>In a randomized, double-blind, placebo-controlled trial, 60 patients post-anal fistulotomy received daily topical ultrasonically nebulized CPD (n = 30) or placebo (n = 30).

Primary endpoints were healing time and scores for edema, pain, and exudation on days 3 and 7. Secondary outcomes included inflammatory cytokine levels, hydroxyproline, angiogenesis, and direct histological and ultrastructural assessment of NETs in granulation tissue. To dissect the underlying mechanism, we investigated the effect of CPD on NETosis in primary human neutrophils, measuring NET formation, reactive oxygen species (ROS) generation, and expression of key mediators (CitH3, PAD4).</p>Results<p>CPD significantly shortened wound healing time (40.23 ± 9.61 vs. 45.84 ± 13.29 days, P < 0.001) and improved clinical scores.