Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of the effect of Astragalus membranaceus (A. membranaceus) on lung adenocarcinoma at the molecular level to elucidate the specific targets according to the network pharmacology approach.@*METHODS@#The active components of A. membranaceus and their potential targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database. Lung adenocarcinoma-associated genes were acquired based on GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, and Therapeutic Targets databases. The PI3K/AKT signaling pathway-related genes were obtained using Reactome portal. Networks of "ingredient-target" and "ingredient-target-pathway-disease" were constructed using the Cytoscape3.6.0 software. The relationships among targets were analyzed according protein-protein interaction (PPI) network. Finally, molecular docking was applied to construct the binding conformation between active ingredients and core targets. Cell counting kit 8 (CCK8) and Western blot assays were performed to determine the mechanism of the key ingredient of A. membranaceus.@*RESULTS@#A total of 20 active components and their 329 targets, and 7,501 lung adenocarcinoma-related genes and 130 PI3K/AKT signaling pathway-related genes were obtained. According to Venn diagram and PPI network analysis, 2 mainly active ingredients, including kaempferol and quercetin, and 6 core targets, including TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR, were identified. The two important active ingredients of A. membranaceus, kaempferol and quercetin, exert the therapeutic effect in lung adenocarcinoma partly by acting on the 6 core targets (TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR) of PI3K/AKT signaling pathway. Expressions of potential targets in lung adenocarcinoma and normal samples were analyzed by using UALCAN portal and found that ERBB2 was overexpressed in lung adenocarcinoma tissues and upregulation of it correlated with clinicopathological characteristics. Finally, quercetin repressed viabilities of lung adenocarcinoma cells by targeting ERBB2 on PI3K/AKT signaling confirmed by CCK8 and Western blot.@*CONCLUSION@#Our finding unraveled that an active ingredient of A. membranaceus, quercetin, significantly inhibited the lung adenocarcinoma cells proliferation by repressing ERBB2 level and inactivating the PI3K/AKT signaling pathway.

Systematic efficacy study and mechanism prediction of Chaihu Plus Mangxiao Decoction in treatment of constipation based on network pharmacology model / 中草药

Objective: To investigate the function network and potential mechanisms of effects of Chaihu Plus Mangxiao Decoction in the treatment of functional constipation by using network pharmacology methods. Methods: TCMSP, TCMID, and Swiss Target Prediction online prediction databases were used to screen the components and their potential targets of Chaihu Plus Mangxiao Decoction using oral availability (OB) and drug-like (DL) as the qualification conditions. PubMed, CTD, TTD, and DrugBank were used to search functional constipation-related targets. STRING and Cytoscape were used to make targets network visualization, screen the key components and core targets with high a degree of the node; Finally, relevant software was applied to analyze core targets and predict the mechanism. Results: A number of 206 total components of Chaihu Plus Mangxiao Decoction were screened, and there were 998 corresponding targets, which were contained 295 targets associated with functional constipation. According to the analysis, there were 64 key components and 30 core targets involving the Chaihu Plus Mangxiao Decoction-induced treatment of functional constipation. After enrichment analysis and KEGG pathway analysis of 30 core targets, it was found that SCN9A, CFTR, HTR2A, OPRD1, PTGS1, and FGFR1 were involved in regulating biological processes including opioid receptor activity, water balance of the organism, terpenoids and biological receptors and subsequent mediating the function of serotonin receptors, arachidonic acid metabolism, transcriptional regulation of MECP2, cytochrome P450, biogenic amine-binding receptors, PI3K the aberrant expression, tyrosine-protein kinase signaling pathway, and exogenous foreign body stimulation. These biological targets and molecular signaling pathways may play a therapeutic role in the treatment of functional constipation. Conclusion: The mechanism of effect of Chaihu Plus Mangxiao Decoction in the treatment of functional constipation is characterized by multiple targets and pathways. Saponins, flavonoids, and sterols may be the material basis for core functions, and serotonin receptors, opioid receptors and chloride channel-regulated receptors may be key targets of Chaihu Plus Mangxiao Decoction.