2. Academic Validation
  3. Phillyrin promotes flap survival by mitigating pyroptosis through the TLR4/NF-κB/NLRP3 signaling pathway

Phillyrin promotes flap survival by mitigating pyroptosis through the TLR4/NF-κB/NLRP3 signaling pathway

  • Apoptosis. 2026 Jan 10;31(1):36. doi: 10.1007/s10495-025-02248-0.
Jiapeng Deng 1,  Wenrui Kang 2,  An Wang 1,  Jialong Yang 1,  Kaitao Wang 1,  Lekai Quan 1,  Hebin Pan 1,  Weilong Song 1,  Panshen Xu 1,  Dingsheng Lin 3
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325000, China.
  • 2 The First Affiliated Hospital of Wenzhou Medical University, The First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325000, China.
  • 3 Department of Orthopedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, The Second School of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325000, China. [email protected].
PMID: 41518527 DOI: 10.1007/s10495-025-02248-0
Abstract

Background: FLAP transplantation is a widely used for wound reconstruction but continues to carry a substantial risk of postoperative necrosis. We evaluated the therapeutic effect of phillyrin for improving FLAP survival and elucidated its underlying pharmacological mechanisms.

Methods: In vivo, a McFarlane FLAP model was established on the dorsal skin of rats. Animals were assigned to four groups: control, low-dose (17.5 mg/kg/day, intraperitoneal [i.p.]), medium-dose (35 mg/kg/day, i.p.), and high-dose (70 mg/kg/day, i.p.) phillyrin. At 7 days postoperatively, we evaluated FLAP survival, blood perfusion, oxidative stress, cytokine expression, Toll-like Receptor 4/nuclear factor κB/NOD-like Receptor protein 3 (TLR4/NF-κB/NLRP3) axis activity, and Pyroptosis. In vitro, human umbilical vein endothelial cells were treated with hypoxia/reoxygenation or lipopolysaccharide/nigericin models, to investigate the protective effects of phillyrin against inflammation-related pyroptotic injury.

Results: Phillyrin improved FLAP survival, significantly enhanced local blood perfusion, reduced neutrophil infiltration, and mitigated oxidative stress. Its mechanism of action is closely associated with the inhibition of the TLR4/NF-κB/NLRP3 axis: phillyrin significantly downregulated pathway activity, reduced cytokines secretion, and decreased the expression of pyroptosis-related effector proteins. In vitro, phillyrin demonstrated anti-inflammatory and anti-pyroptotic cytoprotective effects in H/R and inflammatory injury models by modulating the TLR4/NF-κB/NLRP3 axis.

Conclusion: Phillyrin improves FLAP survival by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway, suppressing excessive inflammation and alleviating ischemia-reperfusion injury.

Keywords

Flap; Inflammation; Phillyrin; Pyroptosis; TLR4/NF-κB/NLRP3.

Figures
Products