Chicoric acid regulates IL-1β to improve the inflammatory response in mice undergoing myomectomy under propofol...

Surgical excision of uterine fibroids triggers acute inflammation, impacting postoperative recovery. Propofol anesthesia may modulate this response. Chicoric acid possesses anti-inflammatory properties, but its perioperative utility remains unexplored.

To investigate whether preoperative chicoric acid enhances the anti-inflammatory effect of propofol in a mouse model of myomectomy and to explore the involvement of the p38 MAPK/NF-κB/IL-1β axis.

A human uterine fibroid xenograft mouse model was established using CB-17 SCID mice. Mice underwent simulated myomectomy under propofol or ketamine anesthesia, with or without preoperative chicoric acid (50 mg/kg, 7 days). Controls included sham and model groups. The p38 MAPK/NF-κB agonist LPS and the IL-1β blocker Rilonacept were used to probe mechanisms. Inflammatory cytokines (MSD), pathway protein expression (Western blot), and uterine histopathology (H&E) were assessed 12h post-surgery.

Propofol anesthesia significantly inhibited surgery-induced p38 MAPK/NF-κB activation and reduced levels of inflammatory cytokines compared with the model group. Preoperative cholic acid further suppressed this pathway and enhanced the anti-inflammatory effect beyond that of propofol alone. LPS reversed chicoric acid's effects, confirming the involvement of the pathway. Unexpectedly, Rilonacept did not enhance but rather reversed the anti-inflammatory effect of chicoric acid, suggesting complex, compensatory interactions within a cytokine network.

Preoperative chicoric acid augments propofol's anti-inflammatory effect during myomectomy by inhibiting the p38 MAPK/NF-κB pathway. However, the paradoxical effect of IL-1β blockade reveals unforeseen complexity in the perioperative cytokine network, warranting further investigation into the multitarget effects of chicoric acid and potential network-compensation mechanisms.