Mechanism of astragaloside Ⅳ alleviating PC12 cell injury by activating PI3K/AKT signaling pathway: based on network pharmacology and in vitro experiments / 中国中药杂志

In this study, the molecular mechanism of astragaloside Ⅳ(AS-Ⅳ) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-Ⅳ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-Ⅳ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-Ⅳ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-Ⅳ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-Ⅳ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-Ⅳ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-Ⅳ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-Ⅳ.

Inhibition of component TZT-5 from leaves of Tripterygium wilfordii on rheumatoid arthritis in rats / 中草药

Objective: To investigate the anti-inflammatory, especially the inhibitory effects of TZT-5, an active component from the leaves of Triterygium wilfordii, on the rheumatoid arthritis of rats and to explore its pharmacodynamic effect using an arthritic model of rats. Methods: The ear swelling model induced by croton oil in mice, paw edema model induced by carrageenin in rats, chicken collagen II (CCII)-induced arthritic model, and adjuvant-induced arthritic (AIA) model in rats were established, respectively. The in vivo anti-inflammatory and inhibitory effects of TZT-5 on the rheumatoid arthritis of rats were observed. Results: TZT-5 could alleviate the symptoms of the above four inflammation animal models, ameliorate the infiltration of inflammatory cells in synovium, and inhibit the proliferation of synovial cells in both CCII-induced arthritic models and AIA models of rats. Conclusion: TZT-5 has the ideal anti-inflammatory effects on CCII-induced arthritic model and AIA model of rats and it is a candidate as a new anti-rheumatoid arthritis drug.