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

Abstract: Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusion: 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.