Berberine chloride alleviated intestinal inflammation and improved postoperative ileus by regulating macrophage polarization via PI3K/AKT signaling pathway

Objective: The aim of this study was to explore the therapeutic effect of berberine chloride (BBR) on postoperative ileus (POI) and unravel the mechanism by which BBR alleviates POI.

Methods: A POI model was established in mice through intestinal manipulation (IM). The impact of BBR on gastrointestinal motility and inflammation was assessed 24 h post-IM by evaluating gastrointestinal transit (GIT), cytokine expression, leukocyte infiltration and macrophage polarization in POI mice. Network pharmacology analysis was employed to explore the mechanism of BBR's action on POI. Bone marrow derived macrophages (BMDMs) were isolated for in vitro culture, and the influences of BBR on cell viability, cytokine production, macrophage polarization and the PI3K/Akt signaling pathway in BMDMs were evaluated.

Results: BBR administration significantly attenuated the intestinal motility dysfunction, reduced leukocyte infiltration, inflammatory mediator expression, and M1 macrophage polarization in the intestinal muscularis of POI mice. Network pharmacology analysis indicated that BBR may exert anti-inflammatory effects on POI via the PI3K/Akt signaling pathway. In vitro studies demonstrated that BBR inhibited macrophage activation and M1 macrophage polarization without affecting M2 macrophage polarization. Further analysis showed that BBR inhibited M1 macrophage polarization by downregulating PI3K expression and Akt phosphorylation, while 740 Y-P, a PI3K pathway agonist, reversed this effect.

Conclusion: BBR markedly alleviates manipulation-induced intestinal inflammation in muscular tissue and restores intestinal transit in POI mice. Mechanistically, BBR exerts anti-inflammatory effects on POI by inhibiting M1 macrophage polarization via regulating the PI3K/Akt signaling pathway.

Berberine chloride; Inflammation; Macrophage polarization; PI3K/AKT; Postoperative ileus.