Compound phellodendron decoction promotes post-fistulotomy wound healing by downregulating neutrophil extracellular traps formation: evidence from a randomized trial and mechanistic studies
In brief
Compound Phellodendron treatment cuts fistulotomy healing time by about six days
In a double-blind trial of 60 patients, topical Compound Phellodendron treatment shortened average healing time after anal fistulotomy from about 46 days to 40 and improved clinical scores. Treated wounds had fewer neutrophil extracellular traps, while lab tests linked the effect to reduced oxidative signaling; whether the benefit extends beyond this small trial remains unknown.
- Journal
- Frontiers in pharmacology (Q1)
- Published
- 15 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Ju Wang, Heng Deng, Shuo Chen, Hui Liu
- PMID
- 42812331
- DOI
- 10.3389/fphar.2026.1732119
Why clinicians should know about it
- Picked for Histology (top studies of the week, 4 October 2026): High-quality evidence in a top journal
- Picked for Anesthesiology and Pain Medicine (top studies of the week, 4 October 2026): randomized trial shows CPD accelerates wound healing
Abstract
BACKGROUND: Persistent inflammation and dysregulated neutrophil extracellular traps (NETs) are key factors impairing postoperative wound healing. 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. METHODS: 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). RESULTS: CPD significantly shortened wound healing time (40.23 ± 9.61 vs. 45.84 ± 13.29 days, P < 0.001) and improved clinical scores. It modulated inflammation by elevating IL-2 and IL-10 while reducing IL-6, IL-22, and TNF-α. Critically, immunofluorescence and transmission electron microscopy revealed a substantial reduction in NETosis in CPD-treated tissues, accompanied by enhanced angiogenesis. In vitro, CPD dose-dependently inhibited PMA-induced NETosis, an effect mediated by reduced ROS generation and decreased PAD4 protein abundance. CONCLUSION: CPD facilitates wound healing through a dual mechanism involving systemic immunomodulation and attenuation of NETosis by the ROS/PAD4 axis in neutrophils. Our study identifies CPD as a promising NETosis-targeted therapeutic agent for chronic wound management.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.