Background:Studies have indicated that Sinomenii Caulis (SC) has several physiological activities, such as anti-inflammatory, anti-cancer, immunosuppression, and so on. SC is currently widely used in the treatment of rheumatoid arthritis, skin disease, and other diseases. However, the mechanism of SC in the treatment of ulcerative colitis (UC) remains unclear.Aims:To predict the active components of SC and determine the mechanism of SC on UC.Methods:Active components and targets of SC were screened and obtained by TCMSP, PharmMapper, and CTD databases. The target genes of UC were searched from GEO (GSE9452), and DisGeNET databases. Based on the String database, Cytoscape 3.7.2 software, and David 6.7 database, we analyzed the relationship between SC active components and UC potential targets or pathways. Finally, identification of SC targets in anti-UC by molecular docking. GROMACS software was used to perform molecular dynamics simulations of protein and compound complexes and to perform free energy calculations.Results:Six main active components, 61 potential anti-UC gene targets, and the top 5 targets with degree value are IL6, TNF, IL1β, CASP3, and SRC. According to GO enrichment analysis, the vascular endothelial growth factor receptor and vascular endothelial growth factor stimulus may be relevant biological processes implicated in the treatment of UC by SC. The KEGG pathway analysis result was mainly associated with the IL-17, AGE-RAGE, and TNF signaling pathways. Based on molecular docking results, beta-sitosterol, 16-epi-Isositsirikine, Sinomenine, and Stepholidine are strongly bound to the main targets. Molecular dynamics simulation results showed that IL1B/beta-sitosterol and TNF/16-epi-Isositsirikine binding was more stable.Conclusion:SC can play a therapeutic role in UC through multiple components, targets, and pathways. The specific mechanism of action needs to be further explored.

2023-01-01·Journal of Theoretical Biology

Application of a count data model to evaluate the anti-metastatic efficacy of QAP14 in 4T1 breast cancer allografts

Article

作者: Guo, Yuchen ; Yong, Ling ; Zhou, Tianyan ; Jian, Weizhe ; Han, Mengyi ; Yao, Qingyu ; Xue, Junsheng

Dopamine D1 receptor (D1DR) is proved to be a promising target to prevent tumor metastasis, and our previous studies showed that QAP14, a potent anti-cancer agent, exerted inhibitory effect on lung metastasis via D1DR activation. Therefore, the purpose of the study was to establish count data models to quantitatively characterize the disease progression of lung metastasis and assess the anti-metastatic effect of QAP14. Data of metastatic progression were collected in 4T1 tumor-bearing mice. Generalized Poisson distribution best described the variability of metastasis counts among the individuals. An empirical PK/PD model was developed to establish mathematical relationships between steady plasma concentrations of QAP14 and metastasis growth dynamics. The latency period of metastasis was estimated to be 12 days after tumor implantation. Our model structure also fitted well to other D1DR agonists (fenoldopam and l-stepholidine) which had inhibitory impact on breast cancer lung metastasis likewise. QAP14 40 mg/kg showed the best inhibitory efficacy, for it provided the longest prolongation of metastasis-free periods compared with fenoldopam or l-stepholidine. This study provides a quantitative method to describe the lung metastasis progression of 4T1 allografts, as well as an alternative PD model structure to evaluate anti-metastatic efficacy.

2022-01-01·Contrast Media & Molecular Imaging4区 · 医学

Mechanism of Jujube (Ziziphus jujuba Mill.) Fruit in the Appetite Regulation Based on Network Pharmacology and Molecular Docking Method

4区 · 医学

ArticleOA

作者: Yue, Rensong ; Shen, Tao ; Zhu, Yu ; Huang, Ju

Objective. To investigate the mechanism of jujube (Ziziphus jujuba Mill.) in appetite regulation based on network pharmacology. Methods. The active components and action targets of jujube were retrieved through the TCMSP and TCMID databases. GeneCards, DisGeNet, Therapeutic Target Database, and OMIM were used to screen the related targets for appetite, appetite suppression, and appetite regulation, and the intersection target of the two was selected. A protein‐protein interaction (PPI) network was constructed. Important protein nodes and subnets were predicted based on the cytoHubba plug‐in, and the hub gene was screened. Additionally, GO and KEGG pathway analyses were performed to obtain potential biological processes and signaling pathways of key targets. And the active ingredient‐target‐action pathway diagram was constructed. Results. A total of 16 active components were screened from jujube, including 131 action targets related to appetite and appetite regulation. Three key targets (MAOA, MMP2, and HSPB1) were screened out by MCODE analysis. KEGG enrichment analysis was mainly enriched in neuroactive ligand‐receptor interaction, serotonin‐containing synapse, gap junction, cAMP signaling pathway, and dopaminergic synapse. Molecular docking results showed that the components coclaurine, (−)‐catenin, (+)‐stepholidine, berberine, cianidanol, coclaurine, and moupinamide in jujube had strong binding activity to the main targets (ESR1, ADRA2C, and MMP2). Conclusion. Based on network pharmacology, the appetite modulating effects of jujube on multiple components, targets, and channels were explored, and the main active components of jujube were predicted to act on multiple signaling pathways to regulate appetite. The molecular docking results showed that the components in jujube had strong binding activity to the main targets, which provided new ideas and methods to further investigate the mechanisms of appetite regulation by jujube.

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适应症	国家/地区	公司	日期
注意缺陷障碍伴多动	中国	云南红河制药科技发展有限公司	1995-01-01
头痛	中国	云南红河制药科技发展有限公司	1995-01-01
偏头痛	中国	云南红河制药科技发展有限公司	1995-01-01
Tourette 综合征	中国	云南红河制药科技发展有限公司	1995-01-01