ABSTRACT
Aim To study the potential molecular anti-inflammatory mechanism of Aconitum tanguticum based on network pharmacology methods,molecular docking technology and cell experiment. Methods The active ingredients targets and disease targets of Aconitum tanguticum were collected through literature and database. The common targets were utilized by mixture of them and the core targets were obtained by constructing the protein protein interaction(PPI)network. Then the component-target-disease network diagram was constructed. The gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)analysis were performed for common targets. AutoDock Vina(1.1.2)software was utilized for combining some of the core targets and the diterpenoid alkaloids in the chemical components of Aconitum tanguticum. Finally,the influence of alcoholic extract of Aconitum tanguticum(ATS)on RAW264.7 cell inflammation model was preliminarily verified by MTT assay,Griess reagent and realtime RT-PCR. Results A total 17 main active ingredients were obtained from literature and 284 common targets were obtained via intersecting with disease targets. Altogether 108 pathways were screened by KEGG enrichment,mainly including PI3K-Akt,Ras,MAPK and HIF-1. Molecular docking results indicated that the active ingredients of Aconitum tanguticum had a high affinity with the core target to be docked. In vitro experiment suggested that ATS treatment inhibited LPS-induced NO production and iNOS mRNA in RAW264.7 cells. Realtime RT-PCR detection suggested that ATS played an anti-inflammatory effect by regulating the PI3K-Akt signaling pathway. Conclusions Aconitum tanguticum exerts anti-inflammatory effects through PI3K-Akt pathways,which provides the scientific basis for better promoting the development of Aconitum tanguticum.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of chronic stress on the spatial learning-memory and the role of glial cell line-derived neurotrophic factor (GDNF) of prefrontal cortex (PFC) and hippocampus (HP) in different age mice.</p><p><b>METHODS</b>The chronic stress model mice in 21 days with multiple chronic unpredictable stressors were applied. The spontaneous behavior and spatial learning-memory ability of mice were tested, using Open field and Morris water maze task, and the expression of GDNF in HP and PFC were detected by immunohistochemical method.</p><p><b>RESULTS</b>Compared with young mice, the spontaneous behaviors were significantly decreased and the spatial learning-memory function were significantly decreased (P < 0.05, P < 0.01) in aged mice. The GDNF expression in the CA3, DG of HP and PFC were significantly reduced in aged mice (P < 0.05, P < 0.01). After chronic stress, the spontaneous behaviors were remarkably decreased and the ability of spatial learning-memory of the stress group mice were significantly decreased (P < 0.05, P < 0.01) compared with those of the control group mice. The expression of GDNF in HP and PFC were remarkably reduced (P < 0.05, P < 0.01) in stress group mice. The aged stress mice had more serious changes after chronic stress.</p><p><b>CONCLUSION</b>The brain aging and chronic stress in mice causes behavioral changes and the damage of spatial learning-memory function, and which may be nearly related to the expression of GDNF in HP and PFC.</p>