Exploration in the Mechanism of Ginsenoside Rg5 for the Treatment of Osteosarcoma by Network Pharmacology and Molecular Docking.

OBJECTIVE: Osteosarcoma is a primary malignancy originating from mesenchymal tissue characterized by rapid growth, early metastasis and poor prognosis. Ginsenoside Rg5 (G-Rg5) is a minor ginsenoside extracted from Panax ginseng C.A. Meyer which has been discovered to possess anti-tumor properties. The objective of current study was to explore the mechanism of G-Rg5 in the treatment of osteosarcoma by network pharmacology and molecular docking technology. METHODS: Pharmmapper, SwissTargetPrediction and similarity ensemble approach databases were used to obtain the pharmacological targets of G-Rg5. Related genes of osteosarcoma were searched for in the GeneCards, OMIM and DrugBank databases. The targets of G-Rg5 and the related genes of osteosarcoma were intersected to obtain the potential target genes of G-Rg5 in the treatment of osteosarccoma. The STRING database and Cytoscape 3.8.2 software were used to construct the protein-protein interaction (PPI) network, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. AutoDock vina software was used to perform molecular docking between G-Rg5 and hub targets. The hub genes were imported into the Kaplan-Meier Plotter online database for survival analysis. RESULTS: A total of 61 overlapping targets were obtained. The related signaling pathways mainly included PI3K-Akt signaling pathway, Proteoglycans in cancer, Lipid and atherosclerosis and Kaposi sarcoma-associated herpesvirus infection. Six hub targets including PIK3CA, SRC, TP53, MAPK1, EGFR, and VEGFA were obtained through PPI network and targets-pathways network analyses. The results of molecular docking showed that the binding energies were all less than -7 kcal/mol. And the results of survival analysis showed TP53 and VEGFA affect the prognosis of sarcoma patients. CONCLUSION: This study explored the possible mechanism of G-Rg5 in the treatment of osteosarcoma using network pharmacology method, suggesting that G-Rg5 has the characteristics of multi-targets and multi-pathways in the treatment of osteosarcoma, which lays a foundation for the follow-up experimental and clinical researches on the therapeutic effects of G-Rg5 on osteosarcoma.

Anthelmintic activity of steroidal saponins from Dioscorea zingiberensis C. H. Wright against Dactylogyrus intermedius (Monogenea) in goldfish (Carassius auratus).

Dactylogyrus intermedius is one of the most pathogenic monogenean parasites on the gills of captive fish and can cause serious problem in aquaculture. To attempt controlling this parasite and explore novel potential antiparasitic agents, the present study was designed to investigate the anthelmintic activity of Dioscorea zingiberensis C. H. Wright against D. intermedius in goldfish under in vivo conditions. Bioactivity-guided fractionation and isolation of the compounds responsible for anthelmintic activity was carried out with the ethanolic extract yielding two bioactive compounds. Using MS, (1)H NMR, (13)C NMR spectroscopic analyses, the two compounds were identified as trillin and gracillin. The results of in vivo anthelmintic efficacy assay showed that the 48-h median effective concentrations (EC(50)) are 26.48 mg L(-1) for trillin and 0.18 mg L(-1) for gracillin. The 48-h acute toxicity tests (LD(50)) of trillin and gracillin were found to be 73.11 and 1.40 mg L(-1) for goldfish, respectively. The resulting therapeutic indices for the two active compounds are 2.76 and 7.78, respectively. These data confirmed that both trillin and gracillin are effective against D. intermedius, and the gracillin exhibits more interesting perspectives for the development of a candidate antiparasitic agent.

In vivo anthelmintic activity of five alkaloids from Macleaya microcarpa (Maxim) Fedde against Dactylogyrus intermedius in Carassius auratus.

The present study aims to evaluate the anthelmintic properties of aerial part of Macleaya microcarpa (Maxim) Fedde. Bioassay-guided fractionation and isolation of the compounds with anthelmintic activity were performed on the ethanolic extract of M. microcarpa yielding five bioactive alkaloids namely: sanguinarine, cryptopine, beta-allocryptopine, protopine and 6-methoxyl-dihydro-chelerythrine by comparing spectral data (UV, NMR, and EI-MS) with literature values. According to in vivo anthelmintic assays, they were found to be 100% effective at the concentrations of 0.7, 8.0, 8.0, 16.0 and 7.0 mgl(-1), and the median effective concentration (EC(50)) values for the five compounds were 0.37, 3.31, 4.64, 8.13 and 3.63 mgl(-1), respectively. Additionally, the acute toxicity on goldfish for the five active compounds was also investigated with median lethal concentrations (LC(50)) values of 1.13, 16.12, 15.88, 21.69 and 10.91 mgl(-1), respectively. The resulting therapeutic indices for sanguinarine, cryptopine, beta-allocryptopine, protopine and 6-methoxyl-dihydro-chelerythrine were 3.03, 4.82, 3.40, 2.66 and 2.99 correspondingly. Correlations analysis between the logP and EC(50), LC(50) of the five alkaloids revealed that the activity of the five alkaloids was well correlated with their hydrophobicity and r(2)=0.45 is for anthelmintic activity while r(2)=0.47 is for acute toxicity for goldfish, respectively. These results provided evidence that the studied plant extract, as well as the isolated compounds, especially sanguinarine, might be potential plant-based medicines for the treatment of D. intermedius infection.