The Metabolic Regulation Effect And Mechanism Study Of Qingfei Paidu Decoction On Pneumonia Models

Objective:Qingfei Paidu Decoction(QPD)has definite anti-COVID-19 effect,while the mechanism remains unclear.In our study,the regulation effect of QPD on endogenous metabolism of the body were investigated,and the anti-inflammtory effect of QPD containing serum was also studied in vitro.Methods:1.Normal rats were orally administrated with different dosage of QPD for 5d,15 d,29d,and the serum samples were analyzed with untargeted metabolomics.2.The protective effect of QPD was evaluated on lipopolysaccharide(LPS)induced pneumonia rat model,and serum and lung samples were analyzed with untargeted metabolomics.3.The anti-pneumonia effect of QPD was evaluated on pneumonia mice induced by cold-humid environment exposure combined with human Hco V 229 E virus infection,and serum and lung samples were analyzed with untargeted metabolomics.4.QPD containing serum was used to observe its effect on the expression of inflammatory cytokines in LPS-induced J774 A.1 macrophages.Results:1.Short-term intervention of QPD(5 days)can regulate endogenous serum metabolites in normal rats.The regulated metabolites are mainly glycerophospholipids and fatty acids,and unsaturated fatty acid biosynthesis,glycerophospholipids metabolism,linoleic acid metabolism pathways were regulated by QPD.Long-term intervention of QPD(15 days and 29 days)can regulate endogenous serum metabolites in normal rats.It mainly regulates glycerophospholipids metabolism,arachidonic acid metabolism,linoleic acid metabolism,primary bile acid biosynthesis,phenylalanine metabolism,etc.Both short-and long-term intervention of QPD regulated inflammation,immune regulation regulated pathways.2.Multiple metabolic pathways related to inflammation and oxidative stress were altered in LPS-induced pneumonia model rats.QPD(Preventive administration)regulated lung glycerophospholipids and linoleic acid metabolism pathway of LPS-induced pneumonia model rats.QPD(therapeutic administration)regulated and restored the whole metabolism of the model rats,especially on serum amino acids metabolism,and lung glutathione metabolism,riboflavin metabolism,pantothenate and Co A biosynthesis.3.Cold-humid environment worsened HCo V 229 E virus induced immune fuction decline.Both cold-humid environment and HCo V 229 E virus impacted host metabolism.QPD significantly regulated the immune function of the pneumonia mice,reduced the level of inflammatory factors in lung tissue,and to a certain extent regulated the metabolism of the body,especially restored the levels of serum amino acids and downregulated lung metabolites involved in arachidonic acid metabolism pathway.4.In the LPS-induced mononuclear macrophage J774 A.1 cell inflammatory model,QPD containing serum inhibited the gene expression of proinflammatory cytokines,thus showed the anti-inflammation effect at some extent.Conclusion:1.Short-and long-term intervention of different dosage of QPD induced different kind and number of endogenous metabolites and different pathways of normal rats.While inflammation and immune regulation related metabolites and pathways were influenced by different intervention method of QPD.2.In LPS induced pneumonia rats,the protective effect of QPD was related with its regulatory effect on overall and lung metabolism.3.In pneumonia mice model induced by cold-humid environment combined with HCo V 229 E virus,QPD enhanced the immune function and inhibited inflammation,which was related with the restore of metabolic homeostasis by QPD,especially with the regulation of inflammation and immunity related metabolites and pathways.4.The anti-inflammatory effect of QPD was furtherly evaluated in LPS induced mononuclear macrophage J774 A.1 cell inflammatory model with QPD containing serum.