Study On The Effect Of Polysaccharide On Viral Pneumonia Based On Natural Immune Regulation And Virus Blocking

Acute respiratory infectious disease induced by respiratory virus infection is called viral pneumonia.The emergence of multiple fatal and highly contagious coronaviruses and influenza viruses over recent years emphasizes the severity of viral pneumonia.The emergence of new viruses,mutant strains and drugs resistant strains has greatly reduced the clinical therapeutic effect of existing drugs.Therefore,the demand for developing new drugs for the treatment of viral pneumonia is very urgent.A variety of polysaccharides have antiviral and immunomodulatory activities,combined with the pathogenesis of viral pneumonia,plant polysaccharides are considered to be a safe,effective and not fully exploited new source of drugs,which conducive to the treatment of viral pneumonia.It has become the focal point of attention in the current pharmaceutical field.The purpose of this study is to screen polysaccharides with good therapeutic effect on viral pneumonia from a variety of polysaccharides and clarify its mechanism,in order to provide new choices for the treatment and drug development of viral pneumonia.In this study,Lycium barbarum glycopeptide（Lb Gp）with excellent immunomodulatory activity and high biosafety was selected from Grifola frondosa polysaccharide（GFP）,Lb Gp and Astragalus polysaccharide（APS）through cytotoxicity experiment and immune experiment,and confirmed that Lb Gp can not only promote the proliferation and phagocytosis of macrophages,but also regulate NF-κB signaling pathwayand,promote the reprogramming of macrophage M1 phenotype to M2 phenotype,and increase the proportion of M2 phenotype,so as to effectively inhibit the excessive immune response.This study further confirmed that Lb Gp inhibited SARS-Co V-2 pseudovirus,GX＿P2V,influenza A virus infection in a dose-dependent manner at the cellular level.The inhibition rates of 6 mg/m L Lb Gp on SARS-Co V-2 pseudovirus,GX＿P2V,influenza A virus infection were 99.45%,94.02%,89.38%respectively.TCID₅₀experiment and immunofluorescence experiment confirmed that Lb Gp can exert its antiviral activity by inhibiting the early steps of virus life cycle such as virus adsorption and entry.In addition,A mouse model of viral pneumonia was established by influenza A virus infection to research the therapeutic effect of Lb Gp on viral pneumonia.The results substantiated that the intragastric administration of Lb Gp could increase the survival rate of mice to 43%,improve the symptoms of weight loss,reduce the lung index of mice,and the inhibition rate of lung index reached 59.47%,alleviate the lung pathological damage caused by virus infection.With the results above,this study confirmed that Lb Gp is a promising drug for the treatment of viral pneumonia.Therefore,the mechanism of Lb Gp in the treatment of viral pneumonia was further explored through virus titer and viral load detection experiment,macrophage polarization experiment and immunofluorescence experiment.The results showed that Lb Gp could reduce the viral load of mice lungs,reduce the proportion of M1 phenotype macrophages,promote the transformation of macrophages into M2 phenotype,and regulate the secretion of cytokines.It can treat viral pneumonia through the dual role of antiviral and immune regulation.This study provides theoretical support for the treatment of viral pneumonia with plant polysaccharides,lays a foundation for the effective development and efficient utilization of plant polysaccharides,preliminarily expounds the therapeutic effect and mechanism of Lb Gp on viral pneumonia,and provides a new option for the development of therapeutic drugs for viral pneumonia,which has important scientific significance and wide application value.