Xiang Guo1, Jinyu Ji1, Zhitao Feng2, Xiaoqiang Hou3, Yanan Luo1, Zhigang Mei4. 1. Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei 443002, China. 2. Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei 443002, China; Institute of Rheumatology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei 443003, China. Electronic address: fengzhitao2008@126.com. 3. Institute of Rheumatology, the First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei 443003, China. 4. Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College of China Three Gorges University, Yichang, Hubei 443002, China. Electronic address: meizhigang@ctgu.edu.cn.
Abstract
OBJECTIVE: To explore the potential targets underlying the effect of sinomenine (SIN) on rheumatoid arthritis (RA) by utilizing a network pharmacology approach. METHODS: SIN and its drug targets were identified using network analysis followed by experimental validation. First, the Pharmmapper, UniProt and GeneCards databases were mined for information relevant to the prediction of SIN targets and RA-related targets. Second, the SIN-target gene and SIN-RA target gene networks were created in Cytoscape software followed by the collection of the candidate targets of each component by R software. Eventually, the key targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: Sixty-seven potential targets of SIN and 3797 related targets involved in RA were subjected to network analysis, and the 20 intersection targets indicated the principal pathways linked to RA. Additionally, 16 key targets, which were linked to more than three genes, were determined to be crucial genes. GO analysis showed that 14 biological processes, 5 cellular components and 2 molecular functions were identified, when corrected by a P value ≤ 0.01. Seven related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. CONCLUSION: The present study explored the potential targets and signaling pathways of SIN during the treatment of RA, which may help to illustrate the mechanism (s) involved in the action of SIN and may provide a better understanding of its anti-rheumatoid arthritis effects in terms of inhibiting angiogenesis, synovial hyperplasia, and bone destruction.
OBJECTIVE: To explore the potential targets underlying the effect of sinomenine (SIN) on rheumatoid arthritis (RA) by utilizing a network pharmacology approach. METHODS:SIN and its drug targets were identified using network analysis followed by experimental validation. First, the Pharmmapper, UniProt and GeneCards databases were mined for information relevant to the prediction of SIN targets and RA-related targets. Second, the SIN-target gene and SIN-RA target gene networks were created in Cytoscape software followed by the collection of the candidate targets of each component by R software. Eventually, the key targets and enriched pathways were examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: Sixty-seven potential targets of SIN and 3797 related targets involved in RA were subjected to network analysis, and the 20 intersection targets indicated the principal pathways linked to RA. Additionally, 16 key targets, which were linked to more than three genes, were determined to be crucial genes. GO analysis showed that 14 biological processes, 5 cellular components and 2 molecular functions were identified, when corrected by a P value ≤ 0.01. Seven related signaling pathways were identified by KEGG analysis, when corrected according to a Bonferroni P value ≤ 0.05. CONCLUSION: The present study explored the potential targets and signaling pathways of SIN during the treatment of RA, which may help to illustrate the mechanism (s) involved in the action of SIN and may provide a better understanding of its anti-rheumatoid arthritis effects in terms of inhibiting angiogenesis, synovial hyperplasia, and bone destruction.