Targeting colorectal cancer with Herba Patriniae and Coix seed:Network pharmacology,molecular docking,and in vitro validation

BACKGROUND Herba Patriniae and Coix seed(HC)constitute a widely utilized drug combination in the clinical management of colorectal cancer(CRC)that is known for its diuretic,anti-inflammatory,and swelling-reducing properties.Although its efficacy has been demonstrated in a clinical setting,the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated.AIM To identify the active,CRC-targeting components of HC and to elucidate the mechanisms of action involved.METHODS Active HC components were identified and screened using databases.Targets for each component were predicted.CRC-related targets were obtained from human gene databases.Interaction targets between HC and CRC were identified.A“drug-ingredient-target”network was created to identify the core components and targets involved.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were conducted to elucidate the key pathways involved.Molecular docking between core targets and key components was executed.In vitro experiments validated core monomers.RESULTS Nineteen active components of HC were identified,with acacetin as the primary active compound.The predictive analysis identified 454 targets of the active compounds in HC.Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets,including 30 core targets.GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase(PI3K)/Akt signaling pathway.Molecular docking showed that acacetin exhibited an optimal interaction with AKT1,identifying PI3K,AKT,and P53 as key genes likely targeted by HC during CRC treatment.Acacetin inhibited HT-29 cell proliferation and migration,as well as promoted apoptosis,in vitro.Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K,p-Akt,and survivin,which likely contributed to CRC apoptosis.CONCLUSION Acacetin,the principal active compound in the HC pair,inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.

Anti-lipid-oxidation effects and edible safety evaluation of the oil extracted by a supercritical CO_(2) process from coix seed fermented by Monascus purpureus

The physicochemical properties and composition of coix seed oil produced by Monascus purpureus fermentation and supercritical CO_(2)extraction were determined.Anti-lipid-oxidation and edible safety were evaluated using a cholesterol-fish oil model,acute oral toxicity assay,and genetic toxicity assay in vitro and in vivo,respectively.The results show that the extraction oil from fermented coix seed(FCS-O)had good physicochemical quality and abundant active components with physiological function.In particular,γ-tocotrienol,γ-oryzanol,coixenolide and oleic acid concentrations reached 72.83μg/g,745.96μg/g,9.65 mg/g and 316.58 mg/100 g DW,respectively.The FCS-O exhibited higher antioxidant capability in inhibiting lipid oxidation and peroxidation.Compared to the blank control,the concentrations of 7-ketocholestreol and peroxide only were 8.42μg/mL and 16.16 mmol/kg at 168 h of oxidation(P<0.01).In addition,the FCS-O has been confirmed to be a very safe edible oil,with no acute toxicity(LD50>10 g/kg bw,considered actually non-toxic)and no induced mutagenicity,cytotoxicity or genotoxicity.These results serve as a good safety reference for future application of the oil from fermented coix seed.The development and utilization of this kind of oil will be beneficial as a food,food ingredient,nutritional supplement,or natural food antioxidant to promote good health function.

Anti-tumor effect of coix seed based on the theory of medicinal and food homology

Coix seed is a dry and mature seed of Coix lacryma-jobi L.var.ma-yuen(Roman.)Stapf in the Gramineae family.Coix seed has a sweet,light taste,and a cool nature.Coix seed enters the spleen,stomach,and lung meridians.It has the effects of promoting diuresis and dampness,strengthening the spleen to prevent diarrhea,removing arthralgia,expelling pus,and detoxifying and dispersing nodules.It is used for the treatment of edema,athlete's foot,poor urination,spleen deficiency and diarrhea,dampness and obstruction,lung carbuncle,intestinal carbuncle,verruca,and cancer.The medicinal and health value is high,and it has been included in the list of medicinal and food sources in China,which has a large development and application space.This article reviews the current research achievements in the processing methods and anti-tumor activities of Coix seed and provides examples of its clinical application in ancient and modern times,aiming to provide reference for further research on Coix seed and contribute to its clinical application and development.Through the analysis of the traditional Chinese patent medicines,and simple preparations and related health food of Coix seed queried by Yaozhi.com,the source,function,and dosage form of Coix seed were comprehensively analyzed,with a view of providing a reference for the development of Coix seed medicine and food.

Study on the mechanism of Coix seed in the treatment of colon cancer Based on network pharmacology

Objective:Study on the mechanism of Coix seed in the treatment of colon cancer based on network pharmacology.Methods:The main chemical components of Coix seed were identified by TCMP,and the target sites of drug components were screened.The target of the protein was mapped to the corresponding gene target through the Uniprot database.Genecards database was used to find the target gene of human colon cancer disease,and then the disease gene target was combined with the drug gene target to screen the common target of disease-drug composition,and the STRING platform was used to construct the drug component-disease target protein interaction.(PPI)network model.The Bioconductor database was used to analyze the potential targets,related molecular functions and signaling pathways of cocoon in the treatment of colon cancer by GO and KEGG enrichment.The disease-drug component-target-signal pathway network was established by Cytoscape software.Results:It was found that there are 9 pharmacodynamics and 28 targets related to colon cancer treatment,and GO functional enrichment analysis is based on correction.P<0.05 screened 346 molecular functional related items,including 256 biological processes,48 molecular functions,and 42 cell components.KEGG functional enrichment analysis screened 24 related pathways according to the adjusted P<0.05.Conclusion:PTGS2,AR,ESR1,PGR,ADH1C,AKR1B1,LTA4H,NCOA1,NCOA2 and other related targets may be potential targets for the treatment of colon cancer.

Network pharmacology-based elucidation of molecular biological mechanisms of Kanglaite injection for treatment of non-small cell lung cancer

Objective: To investigate the effective compounds, potential targets and molecular mechanism of Kanglaite injection (KLTi) in the treatment of Non-Small Cell Lung Cancer (NSCLC) based on network pharmacology. Methods: The active compounds and targets of KLTi which extracted and isolated from Coix Seed were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The related genes of NSCLC were obtained by searching the Human Gene Database (GeneCards) and Online Mendelian Inheritance in Man (OMIM). The candidate targets of KLTi in the treatment of NSCLC were obtained after extracting the intersection network. The "drug-component-target-disease" network was constructed with the help of Cytoscape 3.7.2. The Protein- Protein Interaction networks were constructed on the STRING platform and core network modules were screened. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of candidate genes were performed using Metascape platform, and a "pathway-target- compounds" network was constructed to further screen key genes and active compounds. Results: A total of 11 compounds, 22 candidate targets, 206 GO functions and 12 KEGG pathways were obtained. Conclusion: The active compounds of KLTi in the treatment of NSCLC are stigmasterol, stigmasterol α1 and ergosterol. The key targets are PGR, NCOA2, PTGS2, NR3C2, and PTGS1. The core GO functions included receptor activity and binding, neuronal signal transmission and hormone stimulation;KEGG mainly involves cancer pathways, neuroactive ligand-receptor interactions and calcium signaling pathways. This study reveals the molecular biological mechanism of KLTi in the treatment of NSCLC, which is speculated to be related to neuroendocrine, providing a new basis and therapeutic direction for subsequent clinical application and experimental research.