Background:This study investigated the impacts and mechanisms of yunweiling in the management of Functional Constipation(FC)using network pharmacology and experimental research.Methods:Using the Traditional Chinese Me...Background:This study investigated the impacts and mechanisms of yunweiling in the management of Functional Constipation(FC)using network pharmacology and experimental research.Methods:Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Genecard,and Online Mendelian Inheritance in Man(OMIM)databases,a potential gene target for yunweiling in treating FC was found.A pharmacological network was built and viewed in Cytoscape.A protein interac-tion map was created with STRING and Cytoscape.‘clusterProfiler’helped uncover its mechanism.Molecular docking was done with AutoDock Vina.In a constipation mouse model,Western blot was used to assess yunweiling's effectiveness.Results:To investigate yunweiling's therapeutic effects on FC,we employed a loperamide-induced constipation model.Successful model establishment was con-firmed by first black stool time,reduced stool output,and impaired gastrointestinal motility.Yunweiling treatment,especially at high and medium doses,significantly al-leviated constipation symptoms by reducing first black stool time,increasing stool output,and enhancing gastrointestinal motility.HE staining revealed yunweiling's ability to restore colon tissue structure.Yunweiling modulated the expression of key proteins TP53,P-AKT,P-PI3K,RET,and Rai,implicating its involvement in the PI3K-Akt signaling pathway.Comparative analysis showed yunweiling to be more effective than its individual components(shionone,β-sitosterol,and daucosterol)in improving constipation.The combination of yunweiling with TP53 and PI3K-Akt inhibitors fur-ther enhanced its therapeutic effects,suggesting a synergistic mechanism.Conclusions:The integration of network pharmacology and experimental investiga-tions indicated the effectiveness of yunweiling in managing FC,offering essential theoretical support for clinical application.展开更多
基金funded by the TCM Spleen and Stomach Discipline Leader Project of High-level Talents in Yunnan Province (no grant number)TCM Joint Project of Yunnan Provincial Science and Technology Department (grant number 202101AZ070001-209).
文摘Background:This study investigated the impacts and mechanisms of yunweiling in the management of Functional Constipation(FC)using network pharmacology and experimental research.Methods:Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Genecard,and Online Mendelian Inheritance in Man(OMIM)databases,a potential gene target for yunweiling in treating FC was found.A pharmacological network was built and viewed in Cytoscape.A protein interac-tion map was created with STRING and Cytoscape.‘clusterProfiler’helped uncover its mechanism.Molecular docking was done with AutoDock Vina.In a constipation mouse model,Western blot was used to assess yunweiling's effectiveness.Results:To investigate yunweiling's therapeutic effects on FC,we employed a loperamide-induced constipation model.Successful model establishment was con-firmed by first black stool time,reduced stool output,and impaired gastrointestinal motility.Yunweiling treatment,especially at high and medium doses,significantly al-leviated constipation symptoms by reducing first black stool time,increasing stool output,and enhancing gastrointestinal motility.HE staining revealed yunweiling's ability to restore colon tissue structure.Yunweiling modulated the expression of key proteins TP53,P-AKT,P-PI3K,RET,and Rai,implicating its involvement in the PI3K-Akt signaling pathway.Comparative analysis showed yunweiling to be more effective than its individual components(shionone,β-sitosterol,and daucosterol)in improving constipation.The combination of yunweiling with TP53 and PI3K-Akt inhibitors fur-ther enhanced its therapeutic effects,suggesting a synergistic mechanism.Conclusions:The integration of network pharmacology and experimental investiga-tions indicated the effectiveness of yunweiling in managing FC,offering essential theoretical support for clinical application.