Yang Dong1,2, Lin Hao1,2, Kun Fang3, Xiao-Xiao Han4, Hui Yu5, Jian-Jun Zhang6, Long-Jun Cai6, Tao Fan1, Wen-da Zhang1, Kun Pang1, Wei-Ming Ma1, Xi-Tao Wang1, Cong-Hui Han7,8,9. 1. Department of Urology, XuZhou Central Hospital Affiliated to Nanjing University of Chinese Medicine, Jiefang South Road, No. 199, Jiangsu, Xuzhou, China. 2. Department of Clinical Medicine, Xuzhou Medical University, Xuzhou, China. 3. Xuzhou Clinical Medical College of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Xuzhou, China. 4. Center of Reproductive Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China. 5. Yantai Hospital of Traditional Chinese Medicine, Yantai, China. 6. Department of Urology, Suqian People's Hospital of Nanjing Drum-Tower Hospital Group, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China. 7. Department of Urology, XuZhou Central Hospital Affiliated to Nanjing University of Chinese Medicine, Jiefang South Road, No. 199, Jiangsu, Xuzhou, China. 201706014207bjk@ncist.edu.cn. 8. Department of Clinical Medicine, Xuzhou Medical University, Xuzhou, China. 201706014207bjk@ncist.edu.cn. 9. Department of Biotechnology, College of Life Sciences, Jiangsu Normal University, Xuzhou, China. 201706014207bjk@ncist.edu.cn.
Abstract
BACKGROUND: Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). However, there are no previous pharmacological studies on the protective mechanisms of this activity of the plant. Thus, this study aimed to perform a systematic analysis and to predict the potential action mechanisms underlying S. nigrum activity in BC based on network pharmacology. METHODS: Based on network pharmacology, the active ingredients of S. nigrum and the corresponding targets were identified using the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform database, and BC-related genes were screened using GeneCards and the Online Mendelian Inheritance in Man database. In addition, ingredient-target (I-T) and protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and then the pathways directly related to BC were integrated manually to reveal the pharmacological mechanism underlying S. nigrum-medicated therapeutic effects in BC. RESULTS: Seven active herbal ingredients from 39 components of S. nigrum were identified, which shared 77 common target genes related to BC. I-T network analysis revealed that quercetin was associated with all targets and that NCOA2 was targeted by four ingredients. Besides, interleukin 6 had the highest degree value in the PPI network, indicating a hub role. A subsequent gene enrichment analysis yielded 86 significant GO terms and 89 significant pathways, implying that S. nigrum had therapeutic benefits in BC through multi-pathway effects, including the HIF-1, TNF, P53, MAPK, PI3K/Akt, apoptosis and bladder cancer pathway. CONCLUSIONS: S. nigrum may mediate pharmacological effects in BC through multi-target and various signaling pathways. Further validation is required experimentally. Network pharmacology approach provides a predicative novel strategy to reveal the holistic mechanism of action of herbs.
BACKGROUND:Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). However, there are no previous pharmacological studies on the protective mechanisms of this activity of the plant. Thus, this study aimed to perform a systematic analysis and to predict the potential action mechanisms underlying S. nigrum activity in BC based on network pharmacology. METHODS: Based on network pharmacology, the active ingredients of S. nigrum and the corresponding targets were identified using the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform database, and BC-related genes were screened using GeneCards and the Online Mendelian Inheritance in Man database. In addition, ingredient-target (I-T) and protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and then the pathways directly related to BC were integrated manually to reveal the pharmacological mechanism underlying S. nigrum-medicated therapeutic effects in BC. RESULTS: Seven active herbal ingredients from 39 components of S. nigrum were identified, which shared 77 common target genes related to BC. I-T network analysis revealed that quercetin was associated with all targets and that NCOA2 was targeted by four ingredients. Besides, interleukin 6 had the highest degree value in the PPI network, indicating a hub role. A subsequent gene enrichment analysis yielded 86 significant GO terms and 89 significant pathways, implying that S. nigrum had therapeutic benefits in BC through multi-pathway effects, including the HIF-1, TNF, P53, MAPK, PI3K/Akt, apoptosis and bladder cancer pathway. CONCLUSIONS:S. nigrum may mediate pharmacological effects in BC through multi-target and various signaling pathways. Further validation is required experimentally. Network pharmacology approach provides a predicative novel strategy to reveal the holistic mechanism of action of herbs.
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