甘草和发酵甘草提取物通过调节DC-SIGN/Wnt/β-catenin信号轴减轻鸡毒支原体感染

Mycoplasma gallisepticum (MG) is the principal etiological agent of chronic respiratory disease (CRD) in chickens, compromising poultry performance and causing substantial economic losses. Conventional antibiotic therapy is constrained by antimicrobial resistance and drug-residue concerns, creating an urgent need for safe, effective, and environmentally friendly alternatives. Here, we report the first systematic investigation of the molecular mechanism and translational potential of Licorice extract (Let) and its Fermented Licorice extract (FLet) in suppressing MG infection via modulation of the DC-SIGN/WNT signaling axis. In vitro, FLet exhibited stronger growth-inhibitory activity against MG than Let, while Let and FLet showed no detectable cytotoxicity toward HD11 cells within the tested concentration range of 0.02-4 mg/mL.In MG-infected HD11 cells, both Let and FLet reduced the expression of the MG adhesion-associated factor GapA and decreased MG genomic load. In parallel, Let and FLet modulated MG-induced inflammatory responses, as evidenced by decreased TNF-α and IL-1β and increased IL-4 and IL-10 levels, and alleviated MG-induced apoptosis by downregulating Caspase-3 and Bax while upregulating Bcl-2 and Bcl-xL. In vivo, licorice extract or fermented preparation improved body-weight gain and alleviated splenic lesions in MG-infected chickens, and reduced inflammatory and apoptosis-related markers in spleen. Therapeutic efficacy did not differ significantly from tiamulin (p > 0.05). Mechanistic analyses showed that Let and FLet treatment was associated with reduced DC-SIGN expression and changes in Wnt/β-catenin pathway-related molecules.. DC-SIGN knockdown reduced expression of β-catenin and c-Myc, supporting a regulatory role of DC-SIGN over WNT signaling. Collectively, Let and FLet reduced GapA expression and MG genomic load, attenuated cytokine dysregulation, and decreased apoptosis in HD11 cells. In MG-challenged chickens, Let and FLet improved body-weight gain and alleviated splenic lesions. For the evaluated outcomes, no significant differences were detected between the Let/FLet-treated groups and the tiamulin-treated group under the present experimental conditions. These effects were accompanied by reduced DC-SIGN expression and modulation of Wnt/β-catenin pathway-related molecules.