This study systematically explored the underlying mechanism of Rhizoma Coptidis against type 2 diabetes mellitus (T2DM) by using network pharmacology and molecular docking and experimental validation. We retrieved and screened active compounds of Rhizoma Coptidis and corresponding T2DM-related targets across multiple databases. PPI networks of the genes were constructed using STRING, and the core targets were screened via topological analysis. GO and KEGG enrichment analyses were performed by using DAVID. Finally, molecular docking and experimental studies were performed after bioinformatic analysis for verification. There were 14 active compounds and 19 core targets of Rhizoma Coptidis-T2DM, of which quercetin was identified as the main compound and IL6, VEGFA and TNF were the most significant core targets. GO and KEGG enrichment analyses showed that Rhizoma Coptidis ameliorated T2DM by regulating multiple biological processes and pathways. Docking studies indicated that IL6, VEGFA and TNF could stably bind with all active compounds of Rhizoma Coptidis. The results of our experiments revealed that Rhizoma Coptidis could inhibit the expression of IL6 and TNFα and enhance islet cell viability. This study suggests anti-inflammatory therapeutic effects of Rhizoma Coptidis on T2DM, thereby providing a scientific basis and new insight for further research on the antidiabetic effect of Rhizoma Coptidis.
Although data mining methods are extensively used in the rule analysis of famous old traditional Chinese medicine (TCM) experts’ prescriptions for the treatment of hypertension, most of them only mine the association between herbs and herbs, ignoring the importance of symptoms in the disease. This study collected 439 cases of hypertension treated by famous old TCM experts from the FangNet platform. Using the structure network algorithm, the symptom-herb network was constructed, which redefined the importance of herb in disease. Based on the network, 21 driver herbs, 76 herb pairs, and 41 symptom-herb associations were mined. Finally, the basic prescription composed of Gouteng (Uncariae Ramulus cum Uncis), Huanglian (Coptidis Rhizoma), Chuanxiong (Chuanxiong Rhizoma), Gegen (Puerariae Lobatae Radix), Danggui (Angelicae Sinensis Radix), and Huangqin (Scutellariae Radix) was found. These herbs are the most significant among all herbs, and they have a potential correlation with each other. To further verify the rationality of the data mining results, we adopted the network pharmacology method. Network pharmacological analysis shows that the five core targets in the basic prescription include IL6, VEGFA, TNF, TP53, and EGF, which link 10 significant active compounds and 7 important KEGG pathways. It was predicted that anti-inflammatory, antioxidant, vascular endothelial protection, emotion regulation, and ion channel intervention might be the main mechanisms of the basic prescription against hypertension. This study reveals the prescription rule of famous old TCM experts for treating hypertension from a new perspective, which provides a new approach to inherit the academic experience of famous old TCM experts and develop new drugs.
Ulcerative colitis (UC) is among the common autoimmune disease worldwide. Circular RNAs (CircRNAs) are members of the noncoding RNA family (NcRNAs), in addition to its role in numerous biological processes, they are also linked to a vast range of diseases, including UC. Although previous studies looking at many circRNAs, we are still unclear about the physiological and pathological roles of the circRNAs-associated competing endogenous RNA (ceRNA) network in UC. Based on this, we constructed a circRNA–miRNA–mRNA network based on the ceRNA theory by analyzing from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) database. Genes with higher degrees than others in the ceRNA network were selected as central nodes in constructing the corresponding core subnetworks. In order to fully comprehend the biological function of the ceRNA network, we entered all differentially expressed mRNAs (DEmRNAs) which from the ceRNA network into the Database for Annotation and Integrated Discovery (DAVID) for GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses and the STRING for PPI: protein-protein interaction (PPI) network analysis, genes with the degree value > 5 were defined as the hub genes in the regulatory network. In a nutshell, the ceRNA network was composed of 403 circRNA nodes, 5 miRNA nodes, 138 mRNA nodes and 559 edges. 3 core ceRNA subnetworks centered on hsa-miR-342-3p, hsa-miR-199a-5p and hsa-miR-142-3p were reconstructed. The results elucidated that enrichment of 167 GO categories and 14 KEGG pathway terms. The core PPI network was made up of 15 core targets, of which CD44, HIF1A and MMP2 were the most significant core targets. Overall, this study offered a comprehensive and detailed analysis of the fundamental roles that the ceRNA network played in UC, the hub nodes derived from this research may also serve as diagnostic markers and therapeutic targets.
Ulcerative colitis (UC) is a common autoimmune disease worldwide. Circular RNA (circRNA) is a type of noncoding ribonucleic acids (ncRNAs). In addition to their roles in numerous biological processes, circRNAs are also linked to a vast range of diseases including UC. Although previous studies have examined many circRNAs, the physiological and pathological roles of the circRNA-associated competing endogenous RNA (ceRNA) network in UC remain unclear. Thus, we constructed a circRNA-miRNA-mRNA network based on the ceRNA hypothesis by analyzing data from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI-GEO) database. Genes with higher degree values than others in the ceRNA network were selected as central nodes when constructing the corresponding core subnetworks. To fully understand the biological function of the ceRNA network, we entered all differentially expressed mRNAs (DEmRNAs) from the ceRNA network into the Database for Annotation and Integrated Discovery (DAVID), which was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We further entered DEmRNAs into the STRING database for protein-protein interaction (PPI) network analysis. The results elucidated that the ceRNA network comprised 403 circRNA nodes, 5 miRNA nodes, 138 mRNA nodes, and 559 edges. Three core ceRNA subnetworks centered on hsa-miR-342-3p, hsa-miR-199a-5p, and hsa-miR-142-3p were reconstructed in this study. GO and KEGG enrichment analyses identified 167 enriched GO categories and 14 enriched KEGG pathway terms. The core PPI network was composed of 15 core targets, of which CD44, HIF1A, and MMP2 were the most significant. In summary, 3 hub miRNAs (hsa-miR-342-3p, hsa-miR-199a-5p, hsa-miR-142-3p) and 3 hub genes (CD44, HIF1A, and MMP2) might play an important role in the development of UC. These hub nodes, first proposed here, might also be used as potential diagnostic markers and therapeutic targets.
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