Jatrophane Diterpenoids from the Seeds of Euphorbia peplus with Potential Bioactivities in Lysosomal-Autophagy Pathway

Euphopepluanones F−K(1−4),four new jatrophane type diterpenoids were isolated from the seeds of Euphorbia peplus,along with eight known diterpenoids(5−12).Their structures were established on the basis of extensive spectroscopic analysis and X-ray crystallographic experiments.The new compounds 1−4 were assessed for their activities to induce lysosomal biogenesis through LysoTracker Red staining.Compound 2 significantly induced lysosomal biogenesis.In addi-tion,compound 2 could increase the number of LC3 dots,indicating that it could activate the lysosomal-autophagy pathway.

Study on the Action Mechanism of Euphorbia peplus in the Treatment of Alzheimer s Disease Based on UPLC-Q-TOF-MS/MS Combined with Network Pharmacology and Molecular Docking

[Objectives]Based on UPLC-Q-TOF-MS/MS,network pharmacology and molecular docking techniques,the mechanism of Euphorbia peplus in the treatment of Alzheimer s disease(AD)was studied.[Methods]The UPLC-Q-TOF-MS/MS technique was used to rapidly analyze the chemical components of E.peplus.Active components and potential targets of E.peplus were retrieved from TCMSP and Swiss Target Prediction database,and AD targets were screened using GeneCards database.The targets of E.peplus in the treatment of AD were obtained.The PPI network was constructed using String platform,and the network topology of Cytoscape software was used to compute and screen key targets,and the GO and KEGG pathway enrichment analysis was carried out in Metascape database to construct the"component-target-pathway-disease"network.Molecular docking was used to predict the binding properties of active ingredients and targets.[Results]The results of UPLC-Q-TOF-MS/MS showed that 83 compounds were identified from E.peplus,including 19 terpenoids,10 phenolic acids and phenols,16 flavonoids,2 phenylpropanoids,4 coumarins,1 alkaloid,1 anthraquinone and 30 other compounds.The results of network pharmacological analysis showed that 82 active ingredients were screened,and 279 common targets were identified for the treatment of AD,among which the key targets were ALB(albumin),GAPDH(glyceraldehyde triphosphate dehydrogenase),TNF(tumor necrosis factor),AKT1(serine/threonine protein kinase 1),and IL6(interleukin-6).KEGG enrichment analysis showed that key signaling pathways include cancer pathways,lipid and atherosclerosis,Alzheimer s disease,insulin resistance,serotonergic synapses,calcium signaling pathway,cAMP signaling pathway and other signaling pathways.Molecular docking results showed that 14-deoxyandrographolide,dehydroandrographolide,licochalcone B,apigenin and naringenin may be the key components of E.peplus in the treatment of AD.[Conclusions]The results suggest that E.peplus can be used to treat Alzheimer s disease through multi-component,multi-target and multi-pathway.