Panax quinquefolius polysaccharides enhance the therapeutic efficacy of rare ginsenosides in mice infected with Listeria monocytogenes by inhibiting NF-κB and regulating macrophage polarizationOA

Background:This study aims to investigate the therapeutic potential of rare ginsenosides(HTS)derived from Panax quinquefolius stem-leaf saponins(AGS)on LM infected mice,and to explore its synergistic anti LM mechanism with its Panax quinquefolius polysaccharides(AGP).The mechanism by which AGP enhances the efficacy of rare ginsenosides is also explored through macrophage polarization.Methods:HTS was separated from total ginseng saponins;AGP was characterized using UV-Vis,IR spectroscopy,and monosaccharide composition analysis.An in vivo mouse model of LM infection was established,with penicillin and negative control groups.Efficacy was assessed by survival rate,organ bacterial load,ALT levels,inflammatory cytokines,and histopathology.An in vitro model used LTA-induced RAW264.7 macrophages,with NF-κB,CD68,and CD163 mRNA levels detected via qRT-PCR and immunofluorescence.Results:High-dose HTS(20 mg/kg)alone resulted in only 16.7%survival and significant liver injury.In contrast,HTS(5 mg/kg)and AGP(5 mg/kg)co-administration significantly increased survival to 66.7%,reduced hepatic bacterial load and ALT,downregulated IFN-γand IL-1β,and alleviated liver pathology.In vitro,HTS+AGP reduced LTA-induced cytotoxicity,suppressed NF-κB activation,and decreased secretion of NO,TNF-α,and IL-6.It also reversed the LTA-induced M1 macrophage bias by downregulating CD68 and upregulating CD163,increasing the CD163^(+)/CD68^(+) ratio.Conclusion:AGP can enhance the therapeutic effect of HTS on LM infection by alleviating excessive inflammatory response in infected mice,regulating macrophage polarization balance,and providing experimental basis and theoretical support for the development of new anti-resistant bacterial strategies based on natural active ingredients and the rational application of rare saponins.