Arctiin attenuates acute rejection after rat liver transplantation by modulating macrophage polarization via the NF-κB signaling pathway

Background Postoperative rejection following liver transplantation is closely associated with dysregulated macrophage M1/M2 polarization. Arctiin (ARC) exhibits anti-inflammatory activity; however, its role and underlying mechanisms in transplant rejection remain unclear. Methods In vitro THP-1-derived macrophage polarization models were established and treated with ARC; macrophage polarization markers, NF-κB pathway activation and p65 nuclear translocation were detected. In vivo, an orthotopic rat liver transplantation model (Lewis→BN) was established using Kamada's two-cuff technique. Following dose screening in a preliminary experiment, the formal study included Sham, Model, ARC (25 mg/kg), and tacrolimus (TAC, 1 mg/kg) groups. Drugs were administered daily for 7 or 14 days after transplantation. Liver function, histopathological alterations, macrophage polarization, apoptosis, T-cell infiltration, and signaling pathway activation were systematically assessed. Results In vitro data demonstrated that ARC treatment suppressed M1 marker expression and upregulated M2 markers, accompanied by markedly reduced phosphorylation of IKKβ and p65 as well as blocked p65 nuclear translocation. In vivo, compared with the Model group, both ARC and TAC significantly reduced serum ALT, AST, and TBIL levels, increased ALB levels, and alleviated hepatic necrosis and inflammatory infiltration. M1-associated markers were downregulated, whereas M2-associated markers were upregulated. In addition, Bax and cleaved caspase-3 expression levels were decreased, Bcl-2 expression was increased, and the number of TUNEL-positive cells was reduced. The proportion of CD86 + cells decreased, whereas CD206 + cells increased, accompanied by reduced infiltration of CD3 + , CD4 + , and CD8 + T cells. Transcriptomic analysis and Western blotting further demonstrated that ARC inhibited activation of the NF-κB signaling pathway, as evidenced by reduced expression of p-IKKβ and p-P65. Conclusion ARC attenuates acute rejection and improves liver function following rat liver transplantation by modulating the NF-κB signaling pathway, thereby promoting macrophage M2 polarization and reducing inflammation, apoptosis, and T-cell infiltration.