Background: Depression is associated with the abnormal activation of the human inflammatory response system, which is a life-threatening disorder affecting millions of people of all ages around the world. The purposes of the present study were to examine the effect of Lonicera japonica polysaccharide (LJP), a polysaccharide extracted from Lonicera japonica Thunb., on depressed mice treated with the unpredictable emotional stress stimulation. Methods: The components of LJP after extraction were detected by HPLC. Depression model is established through chronic unpredictable stimulation, and the depression behavior was assessed by mouse behavioral assessment, including open field, elevated plus maze, tail suspension, forced swim. Pathological changes in hippocampus of mice were observed by HE and toluidine blue staining. Protein expression of NLRP3 inflammasome pathway was detected by WB.
Objective. Hua-Feng-Dan (HFD) is a Chinese medicine for stroke. This study is to predict and verify potential molecular targets and pathways of HFD against stroke using network pharmacology. Methods. The TCMSP database and TCMID were used to search for the active ingredients of HFD, and GeneCards and DrugBank databases were used to search for stroke-related target genes to construct the “component-target-disease” by Cytoscape 3.7.1, which was further filtered by MCODE to build a core network. The STRING database was used to obtain interrelationships by topology and to construct a protein-protein interaction network. GO and KEGG were carried out through DAVID Bioinformatics. Autodock 4.2 was used for molecular docking. BaseSpace was used to correlate target genes with the GEO database. Results. Based on OB ≥ 30% and DL ≥ 0.18, 42 active ingredients were extracted from HFD, and 107 associated targets were obtained. PPI network and Cytoscape analysis identified 22 key targets. GO analysis suggested 51 cellular biological processes, and KEGG suggested that 60 pathways were related to the antistroke mechanism of HFD, with p53, PI3K-Akt, and apoptosis signaling pathways being most important for HFD effects. Molecular docking verified interactions between the core target (CASP8, CASP9, MDM2, CYCS, RELA, and CCND1) and the active ingredients (beta-sitosterol, luteolin, baicalein, and wogonin). The identified gene targets were highly correlated with the GEO biosets, and the stroke-protection effects of Xuesaitong in the database were verified by identified targets. Conclusion. HFD could regulate the symptoms of stroke through signaling pathways with core targets. This work provided a bioinformatic method to clarify the antistroke mechanism of HFD, and the identified core targets could be valuable to evaluate the antistroke effects of traditional Chinese medicines.
Context
Aucubin (AU), an iridoid glycoside that is one of the active constituents of
Eucommia ulmoides
Oliv. (EUO) (Eucommiaceae), a traditional Chinese medicine, has been extensively studied in the management of neurological diseases (NDs). However, a comprehensive review of its effects and mechanisms in this regard is currently not available.
Objective
To compile the protective effects and mechanisms of AU in NDs and provide a basis for further research.
Methods
We used ‘aucubin’ as the ‘All Fields’ or ‘MeSH’ in PubMed, Web of Science and China National Knowledge Infrastructure without any limitation to search all relevant articles as comprehensively as possible; we selected the articles on AU treatment of NDs for summary.
Results
Studies reviewed herein reported that AU improved the symptoms or prognosis of Parkinson’s disease, Alzheimer's disease, intracerebral haemorrhage, diabetic encephalopathy, epilepsy, anxiety and depression, and traumatic brain injury. The pharmacological mechanisms involved in repairing neuronal loss were postulated to include increasing γ-aminobutyric acid (GABA) content in the synapse, promoting differentiation of neural precursor cells into GABAergic neurons, providing antioxidant and anti-neuroinflammation activities, as well as enhancing autophagy and anti-apoptotic actions.
Discussion and conclusions
The protective effects of AU on some NDs have been confirmed. According to the pharmacological effects, AU is also highly likely to have protective effects on other NDs, which can be realized by further
in vivo
and
in vitro
basic research, and clinical trials. In the future, AU may be used for clinical prevention or treatment of patients with neurological diseases.
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