Abstract
BackgroundSolanum 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.MethodsBased 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.ResultsSeven 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.ConclusionsS. 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.
Highlights
Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC)
To explore the potential primary active ingredients, we evaluated each candidate’s druggability based on its corresponding oral bioavailability (OB) and drug likeness (DL) values predicted in TCMSP database
The network pharmacology approach provides a predicative novel strategy for seeking evidence for the action mechanisms of herbal medicines based on a holistic perspective
Summary
Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). 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. Despite the increased use of multimodality therapy with neoadjuvant chemotherapy followed by radical cystectomy or bladder sparing approaches [4,5,6], the longterm survival rates of patients with muscle-invasive BC have remained largely unchanged for decades [7, 8], and approximately 50% of cases progress to incurable metastatic BC [3, 9]. Five CPIs, including three programmed cell death ligand-1 (PD-L1) inhibitors, namely atezolizumab, avelumab, and durvalumab, and two anti-PD-1 antibodies, nivolumab and pembrolizumab, have been approved by the Food and Drug Administration as systemic therapeutic agents for patients with metastatic and muscle-invasive BCs [3, 10]. CPIs revolutionized the treatment of BC, only approximately 20% of patients respond to immunotherapy, and the overall prognosis remains dismal [3]
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