Network-Based Pharmacology and Experimental Validation to Explore the Portulaca oleracea L.Mechanism of Action in the Treatment of Colorectal Cancer
- VernacularTitle:基于网络药理学与实验验证探究马齿苋治疗结直肠癌的作用机制
- Author:
Sisi REN
1
;
Lu LU
1
;
Jiashu PAN
1
;
Yujing LIU
1
;
Guang JI
1
;
Hanchen XU
1
Author Information
- Publication Type:Journal Article
- Keywords: Portulaca oleracea L; Colorectal cancer; Network pharmacology; Molecular docking; Inflammatory-cancer transformation
- From: World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(9):2265-2277
- CountryChina
- Language:Chinese
- Abstract: Objective To analyze the potential mechanism of action of Portulaca oleracea L.in the treatment of colorectal cancer(CRC)using network pharmacology and experimental verification.Methods With reference to TCMSP and ETCM databases,the effective ingredients and targets of Chinese medicine P.oleracea were obtained,and targets related to CRC were retrieved from Genecards,Drugbank and OMIM databases,which were imported into Venny database,String database and Cytoscape platform to construct the PPI proteins.The common core targets were analyzed for GO function and KEGG pathway enrichment using Metascape database and Microbiology Letter platform,and the active ingredients and key targets were molecularly docked using Autodock and Pymol software.To construct a CRC mouse model and give P.oleracea treatment,observe the histopathological changes of its colon,and validate the key targets using qRT-PCR experiments and Western blot experiments.In addition,quercetin,luteolin,and kaempferol were used to act on HCT116 cells to observe the effects on cell proliferation and calculate the IC50,which was further verified using qRT-PCR assay and Western blot assay.Results Network pharmacological yielded 11 active ingredients and 209 targets corresponding to the target of P.oleracea.Disease targets were 2667.By analyzing the results,it was predicted that the active ingredients such as quercetin,luteolin,and kaempferol were involved in biological processes such as cellular response to lipids through key targets such as IL6,TP53,and IL1β,which were closely related to pathways in cance.Molecular docking showed that quercetin,luteolin,and kaempferol had good affinity for IL6,TP53 and IL1β.In vivo experiments confirmed that P.oleracea significantly inhibited colon tumorigenesis in mice,and inhibited the levels of IL6,IL1β inflammatory factors and increased the expression level of P53 protein.In vitro experiments showed that quercetin,luteolin and kaempferol could inhibit the proliferation of HCT116 cells to different degrees,and luteolin could inhibit the expression of IL6 and IL1β and up-regulate the expression of P53.Conclusion Through network pharmacology,in vivo and in vitro experiments,the"multi-component-multi-target-multi-pathway"effect of P.oleracea in the treatment of CRC has been confirmed,which reveals that inhibition of inflammation and delay of inflammation-cancer transformation may be one of the potential therapeutic pathways,and provides a theoretical basis and research direction for further exploration of the mechanism and clinical application of P.oleracea.
