Preliminary Study On The Inhibitory Effect Of Momordicin Compounds On Lung Adenocarcinoma Cell A549 Through Glycolipid Metabolic Pathway

Lung cancer is a malignant tumor with high morbidity and mortality.However,the current drugs for lung cancer have the disadvantage of high toxicity,and it is of great significance to develop new drugs with low toxicity.The purpose of this paper is to study the separation and purification of momordicin and its mechanism.This study provides a theoretical basis for the application of momordicin in the treatment of lung cancer.In this paper,using literature retrieval to collect balsam pear nucleoside compounds of structural formula,using the Swiss database and Pharm Mapper database to find alternative active ingredient of target genes.Constructing a drug-disease target database,constructing a diabetes,hyperlipidemia and lung adenocarcinoma disease target database by using a Genecards database and a DisGeNET database,and finding the target intersection gene target of the three diseases and the momordicin.The PPI network of intersecting targets was constructed by STRING database,the core gene targets were screened by Cytoscape V3.8.0 software,and analyzed by GO enrichment and KEGG pathway analysis in Metascape database.TIMER2 database,Ualcan database,and Kaplan-Meier Plotter database were used to explore the expression of core gene targets and the survival of patients with lung adenocarcinoma.The molecular docking between the gene target and the corresponding momordicin compound was performed by using AutoDockTools software.Momordicin was isolated from Momordica charantia L.by reflux extraction,and purified by macroporous resin.The structure of the product was determined by infrared spectroscopy.The effects of momordicin on glucose metabolism were studied by determining the inhibition of momordicin on α-amylase and α-glucosidase.The effects of momordicin on lipid metabolism were studied by determining the inhibition of momordicin on pancreatic lipase and the adsorption of oil and cholate.The anti-tumor activity of momordicin in vitro was evaluated by detecting the inhibition of momordicin on lung adenocarcinoma cell line A459 by CCK8 assay.Finally,to explore the effect of momordicin solution on the RNA expression level of lung adenocarcinoma cell line A459 by transcriptome sequencing.Method in this paper,the results are as follows,through the network pharmacology out 14 core gene targets,found in the transcriptome analysis system of EGFR,VDR,PPARG and ICAM1 gene expression,such as core ESR2,ABCB1 gene expression,such as the core system and EGFR,VDR,PPARG and ICAM1 expression in lung adenocarcinoma situation analysis,and ESR2 in lung adenocarcinoma patients survival situation analysis.Bioinformatics analysis also showed that EGFR,ESR1,ICAM1,PPARG and other genes were closely related to the prognosis of lung cancer.GO enrichment analysis and KEGG pathway analysis showed that core gene targets were closely related to inflammatory response,glandular development,immune response regulation,proteoglycan in tumor,chemical carcinogenic-receptor activation,lipid and atherosclerosis.The lowest binding energy of 6 genes,such as ALB,EGFR,ESR1,MMP9,PPARG and TNF,was less than 0 kcal/mol,and the lowest binding energy was-11.61kcal/mol.Momordicin could significantly inhibit the activities of enzymes related to glucose and lipid metabolism,the inhibition rates of α-amylase and α-glucosidase were 90.36%and 92.51%(P<0.001),respectively,and the inhibition rate of pancreatic lipase was 65.54%(P<0.001).In addition,the adsorption rate of momordicin on peanut oil was 65.00%,and the adsorption rates of sodium glycocholate,bovine bile salt and glycocholate were80.36%,69.58% and 82.27%,respectively.At 72 h,the inhibition rate of 160 μg/m L momordicin on lung adenocarcinoma cell line A549 reached 96.21%.Transcriptome sequencing results showed that momordicin significantly affected the transcription of lung adenocarcinoma cell line A549,and 1203 differentially expressed genes were obtained.These genes are closely related to the biological pathways such as cytokine-cytokine receptor pathway,AGE-RAGE signaling pathway,TNF signaling pathway,NF-κB signaling pathway,MAPK signaling pathway,JAK-STAT signaling pathway in diabetic complications.The results show that the isolated from momordica charantia powder of bitter melon have good in vitro sugar and fat resistant,resistant to the vitality of lung adenocarcinoma A549 cells also have stronger inhibitory effect.Transcriptome sequencing and network pharmacology analysis shows momordicin may play an anti-lung adenocarcinoma role by regulating target genes such as GFR,VDR,PPARG,ICAM1,ESR2,ABCB1 and affecting the process of glucose and lipid metabolism.