Résumé
This study aims to explore the anti-depression mechanism of Zuojin Pills based on the plasma constituents, network pharmacology, and experimental verification. UHPLC-TOF-MS was used for qualitative analysis of Zuojin Pills-containing serum. Targets of the plasma constituents and the disease were retrieved from PharmMapper and GeneCards. Then the protein-protein interaction(PPI) network was constructed and core targets were screened for GO term enrichment and KEGG pathway enrichment. Cytoscape 3.7.2 was employed construct the "compound-target-pathway" network and the targets and signaling pathways of Zuojin Pills against depression were predicted. CUMS-induced depression mouse model was established to verify the key targets. The results showed that a total of 21 constituents migrating to blood of Zuojin Pills were identified, which were mainly alkaloids. A total of 155 common targets of the constituents and the disease and 67 core targets were screened out. KEGG enrichment and PPI network analysis showed that Zuojin Pills may play a role in the treatment of depression through AMPK/SIRT1, NLRP3, insulin and other targets and pathways. Furthermore, the results of animal experiments showed that Zuojin Pills could significantly improve the depression behaviors of depression, reduce the levels of IL-1β, IL-6 and TNF-α in hippocampus and serum, activate AMPK/SIRT1 signaling, and reduce the protein expression of NLRP3. In conclusion, Zuojin Pills may play a role in the treatment of depression by activating AMPK/SIRT1 signaling pathway, and inhibiting NLRP3 activation and neuroinflammation in the hippocampus of mice.
Sujets)
Animaux , Souris , Pharmacologie des réseaux , AMP-Activated Protein Kinases , Chromatographie en phase liquide à haute performance , Protéine-3 de la famille des NLR contenant un domaine pyrine , Sirtuine-1 , Médicaments issus de plantes chinoises/pharmacologie , Simulation de docking moléculaireRésumé
This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.
Sujets)
Rats , Animaux , Rat Sprague-Dawley , Dépression/traitement médicamenteux , AMP-Activated Protein Kinases/métabolisme , Protéomique , Hippocampe , Stress psychologique/métabolisme , Sphingolipides/métabolisme , Modèles animaux de maladie humaine , Médicaments issus de plantes chinoisesRésumé
@#Objective To evaluate the methodological quality of clinical practice guidelines of rehabilitation using Appraisal of Guidelines for Research and Evaluation (AGREE) II.Methods Clinical practice guidelines of rehabilitation were searched in databases such as PubMed, EMBASE, Wanfang database, CNKI, China Biology Medicine disc and related websites from medlive.cn, National Institute for Health and Care Excellence, National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, World Health Organization, and Guidelines International Network from establishment to January 11, 2020. Two researchers reviewed literatures and assessed the methodological quality of the guidelines independently by using AGREE II; any disagreements needed to be discussed in a consensus meeting.Results A total of 84 guidelines were included in the study, with 67 foreign guidelines and 17 domestic guidelines. The average score rate for all the guidelines was 48.1%, in which 49.9% for the foreign guidelines and 40.7% for the domestic guidelines. In the six areas of AGREE II, the average score rate of the foreign guidelines was higher than that of domestic ones (|Z| > 2.034, P < 0.05), expect applicability; the average score rate of clarity and independence improved with the launch of AGREE Ⅱ ( Z > 2.130, P < 0.05). The average scores rate ranged from high to low followed as range and purpose (41.6%), clarity (39.9%), participants (24.5%), rigor (23.2%), independence (15.5%) and applicability (12.9%). Conclusion Clinical practice guidelines of rehabilitation is mainly of low quality by AGREE II. Guideline developers need to work after AGREE Ⅱ standard in the future.