Transcriptomics Combined With Proteomics To Screen The Key Pathway Of Mogroside Ⅴ In Alleviating OVA-induced Pulmonary Inflammation In Asthmatic Mice

Objective: Mogroside Ⅴ(MⅤ),a bioactive ingredient extracted from natural function food Siraitia grosevnorii which possess moistening lung and relieving cough activities,but its underlying mechanisms were rarely studied.This study aimed to evaluate the potential ameliorating effect of Mogroside Ⅴ on ovalbumin(OVA)-induced pulmonary inflammation in mice with the help of omics methods,and to gain an system-wide understanding of its mechanism of action.Methods: The asthma model was established in female Balb/C mice induced by ovalbumin,and the appropriate dose of Mogroside Ⅴ was administered to observe the pathological changes of lung tissue and related biochemical indicators.The normal control group(NC),ovalbumin-induced control group(OC)and mogroside Ⅴ administration group(MⅤ)were selected for transcriptomic and proteomic analysis of lung tissues of 3 mice from each group,and the results were conjoint analyzed.Results:(1)Lung histomorphology and H&E staining showed that Mogroside Ⅴ alleviated OVAinduced lung inflammation;Enzyme linked immunosorbent assay(ELISA)results showed that Mogroside Ⅴ effectively reduced the expression levels of inflammatory factors Immunoglobulin E(Ig E),Tumor necrosis factor-α(TNF-α)and Interleukin-5(IL-5)in serum of model mice.(2)RNA-seq analysis showed that compared with normal control group(NC)and ovalbumin-induced control group(OC),a total of 944 differentially expressed genes were screened,of which the expression of 846 genes was up-regulated and 98 genes was downregulated.Compared with ovalbumin-induced control group(OC)and administration group(MⅤ),a total of 449 differentially expressed genes were screened,109 genes level were increased and 340 genes level were decreased;DIA analysis showed that compared with normal control group(NC)and ovalbumin-induced control group(OC),a total of 341 differentially expressed proteins were screened,of which 260 differentially expressed proteins were upregulated and 81 differentially expressed proteins were down-regulated;while the ovalbumin-induced control group(OC)was compared with the administration group(MⅤ),a total of 259 effective differences were screened.Among the expressed proteins,including 63 up-regulated genes and 196 downregulated genes.(3)Combined with transcriptome and proteome analysis,93 related major pathways were screened.We found that mogroside Ⅴ exerts antiinflammatory effects in lung tissue through two signaling pathways,NF-κB and Jak-Stat1.In addition,we also found that key regulatory molecules(Igha,Ighg1,IκB,NF-κB,Jak1,and Stat1)in these two pathways are activated by mogroside Ⅴ in the inflammatory response.Trend analysis based on transcriptomics and proteomics found that at the gene level,there are 454 genes when gene is upregulated in the control group compared with the ovalbumin-induced group and down-regulated in the ovalbumin-induced group compared with the administration group,on the contrary,there are 111;At the protein level,there are 238 proteins on the condiction when protein is up-regulated in control group(NC)compared with ovalbumin-induced group(OC)and is down-regulated in ovalbumin-induced group(OC)compared with administration group(MⅤ),and conversely,there are 91;The gene and protein expression levels of key factors Igha,Ighg1,PI3 K,and Akt in the key PI3K-Akt signaling pathway obtained by comparing the KEGG results of transcriptome and proteome trend analysis were verified,and it was found that the expression levels of these factors were increased significantly after modeling and were significantly inhibited after MⅤ administration.Conclusions: The combination of transcriptomics and proteomics revealed that Mogroside Ⅴ may inhibit the activation of key factors Igha,Ighg1,Jak,Stat1,PI3 K and Akt in the NF-κB,Jak-Stat1 and PI3K-Akt signaling pathways,inhibiting the activation of its pathway,thereby improving OVA-induced lung inflammation in mice to achieve the effect of moistening the lungs and relieving cough,which provides a data framework for further systematic research to understand the mechanism of Mogroside Ⅴ alleviating OVA-induced pulmonary inflammation and also provides a good way to elucidate the internal mechanism of Luo han guo’s nourishes the lungs and relieves cough effect.