Effect and Signaling Pathways of Nelumbinis Folium in the Treatment of Hyperlipidemia Assessed by Network Pharmacology

Objective:In this study,the effects and signaling pathways of Nelumbinis folium in the treatment of hyperlipidemia were analyzed based on network pharmacology and molecular docking.Materials and Methods:The main components and targets of Nelumbinis folium were searched through traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),and the active components were selected according to their oral availability and drug-like properties.The main targets of hyperlipidemia were identified using the Dis Ge NET database.Venny 2.1.0 was used to take the intersection of both targets,which were submitted to the STRING database to construct the protein-protein interaction network model.The Database for Annotation,Visualization and Integrated Discovery 6.7 was used to conduct gene ontology and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses of the targets.Cytoscape 3.7.1 was used to construct the component-target-pathway network.Auto Dock Vina molecular docking software was used to study the binding effect and mechanism of the core components and targets of N.folium.Results:Fifteen active components of N.folium and 195 potential targets were selected through TCMSP,whereas 4216 targets for hyperlipidemia were selected from Dis Ge NET.Further,138 potential cross-targets of hyperlipidemia were identified.A network of component-target-pathway was constructed.Quercetin,kaempferol,and isorhamnetin were the core components,which played an important role in anti-hyperlipidemia,mainly through the non-alcoholic fatty liver disease and insulin resistance(IR)signaling pathways.Molecular docking results showed that quercetin had the lowest docking energies with peroxisome proliferator activated receptorα,peroxisome proliferator-activated receptorγ,INSR-6.20,-10.00,and-8.40(kcal/mol,respectively).The binding mode was mainly hydrogen bonds and van der Waals forces.Conclusions:The active components of N.folium may regulate lipid metabolism by participating in the signaling pathways of non-alcoholic fatty liver disease and IR.

Exploring the Pharmacological Mechanism of Danhe Granules against Hyperlipidemia by Means of Network Pharmacology and Verified by Preliminary Experiments

Objective:This study explored the multicomponent,multitarget,and multipathway mechanism of Danhe granules(DG)against hyperlipidemia through network pharmacology.The relevant targets and pathways were verified by preliminary experiments.Methods:The active components of DG were selected by TCMSP and TCMIP database,and the component-target network diagram was constructed by Cytoscape 3.7.1.The protein–protein interaction network of targets was constructed and core targets were screened out by STRING11.0 database.Metascape database and Cytoscape 3.7.1 were used to enrich the target and establish a hyperlipidemia model in Sprague-Dawley(SD)rats to detect blood lipid and oxidative stress indexes and observed pathological changes of aorta by H and E staining.Results:The results showed that a total of seven active components of DG were screened out,including quercetin,sitosterol,luteolin,kaempferol,etc.There were 127 corresponding targets,including AKT1,tumor necrosis factor,TP53,interleukin-6,RELA,vascular endothelial growth factor,superoxide dismutases,and catalase.It is mainly involved in biological processes such as drug response,regulation of apoptosis,redox reaction,and lipid reaction.There were 573 signal pathways corresponding to the target,including HIF-1 signal pathway,TNF signal pathway,VEGF signal pathway,nonalcoholic fatty liver disease,etc.The experiment verified that DG can reduce the blood lipid of SD rats by regulating the process of oxidative stress.Conclusions:This study made a preliminary study on the pharmacological mechanism of DG against hyperlipidemia and laid the foundation for the research and development of new drugs and subsequent in-depth research.

Mechanism Exploration of the Classical Traditional Chinese Medicine Formula Huoluo Xiaoling Pill in Clinical Treatment and the Traditional Chinese Medicine Theory“Treating Different Diseases with the Same Method”:A Network Pharmacology Study and Molecula Docking Verification

Objective: To analyze the possible mechanism of the Huoluo Xiaoling Pill in the treatment of three diseases, hyperglycemia, hyperlipidemia, and metabolic syndrome, and to provide ideas for learning the mechanism of “Treating different diseases with the same method” in Traditional Chinese Medicine(TCM) theory. Materials and Methods: The Traditional Chinese Medicine System Pharmacology Database and Uni Prot databases were used to screen the main ingredients and targets of the Huoluo Xiaoling Pill. The Gene Cards database was used to screen the targets of the diseases, and Cytoscape 3.7.2 was used to construct a “Drug-Components-Targets-Disease” network to determine the core components. The STRING database was used to construct the protein-protein-interaction network, and gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomics enrichment analyses were carried out on the Metascape database. Auto Dock 1.5.6 was used for molecular docking. Results: A total of 118 active components and 208 targets were screened in the Huoluo Xiaoling Pill. Quercetin, tanshinone IIA, luteolin, and ellagic acid were potential core components of Huoluo Xiaoling Pill treating the three diseases, and interleukin 6, Tumor necrosis factor, and vascular endothelial growth factor were potential key targets. Co-occurring GO biological processes involved responses to the molecules of bacterial origin, and the AGE-RAGE signaling, fluid shear stress, and atherosclerosis pathways were the co-occurring pathways. Molecular docking revealed good docking conditions between screened targets and components. Conclusion: This study predicted the mechanism of the Huoluo Xiaoling Pill in treating the three diseases. At the same time, the co-occurring targets and pathways between the three diseases provided a material basis for the TCM theory, “Treating different diseases with the same method.”