Network pharmacology: curing causal mechanisms instead of treating symptoms

Nogales, Cristian; Mamdouh, Zeinab M.; List, Markus; Kiel, Christina; Casas, Ana I.; Schmidt, Harald

doi:10.1016/j.tips.2021.11.004

Cited by 459 publications

(289 citation statements)

References 114 publications

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“…The active compounds and target genes of traditional herbs have been widely explored by using network pharmacology methods, and it provides a new thought in the research of traditional medicine [ 21 ]. However, some new problems are also emerging, such as mixed research, decentralized and irregular data, and lack of scientific validation [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Study on Mechanism of Yiqi Yangyin Jiedu Recipe Inhibiting Triple Negative Breast Cancer Growth: A Network Pharmacology and In Vitro Verification

Sun

Zhang

et al. 2022

Journal of Oncology

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Background. The present study explores the potential mechanism of Yiqi yangyin jiedu Recipe (YQYYJDR) on triple negative breast cancer via adopting network pharmacology and experimental validation. Materials and Methods. The potential active compounds and target genes of YQYYJDR were screened out from TCMSP database with OB ≥ 30 % and DL index ≥ 0.18 . The potential pathways and function enrichment were identified from Metascape website. MDA-MB-231 and MDA-MB-468 cells were tested for cell viability, invasion, and apoptosis by in vitro and in vivo experiments. Results. A total of 153 bioactive compounds and 281 target genes of YQYYJDR were retrieved from TCMSP database. The top 5 enrichment pathways of YQYYJDR target genes include pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, proteoglycans in cancer, IL-17 signaling pathway, and platinum drug resistance. 65 target genes were included in the pathway of cancer. Biological function enrichment analysis of 65 genes showed YQYYJDR inhibited tumor growth mainly through apoptotic pathway. In vitro experiments showed that YQYYJDR could inhibit the proliferation and invasion of MDA-MB-231 and MDA-MB-468 cells, arrest cells in S stage, and induce cell apoptosis. YQYYJDR upregulated BAX, caspase3, and cleaved caspase3 expression and downregulated BCL2 expression. In vivo experiments showed that YQYYJDR could inhibit tumor growth. Conclusions. In this study, network pharmacology and experiment were used to explore the mechanism of YQYYJDR on triple negative breast cancer. In vitro and in vivo experiments showed that YQYYJDR could inhibit the growth of triple negative breast cancer and induce cell apoptosis. Apoptosis pathway plays a significant role in the treatment of triple negative breast cancer.

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Section: Discussionmentioning

confidence: 99%

Study on Mechanism of Yiqi Yangyin Jiedu Recipe Inhibiting Triple Negative Breast Cancer Growth: A Network Pharmacology and In Vitro Verification

Sun

Zhang

et al. 2022

Journal of Oncology

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“…The paradigm of precision medicine offers an alternative to the traditional "one-fits-all" approach by exploiting the wealth of molecular and clinical data to stratify patients into clinically relevant subgroups with shared molecular disease mechanisms and, hence, offering the potential for mechanism-based treatment strategies [3,4].…”

Section: Introductionmentioning

confidence: 99%

spongEffects: ceRNA modules offer patient-specific insights into the miRNA regulatory landscape

Boniolo

Hoffmann

Roggendorf

et al. 2022

Preprint

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Cancer is one of the leading causes of death worldwide. Despite significant improvements in prevention and treatment, mortality remains high for many cancer types. Hence, innovative methods that use molecular data to stratify patients and identify biomarkers are needed. Promising biomarkers can also be inferred from competing endogenous RNA (ceRNA) networks that capture the gene-miRNA-gene regulatory landscape. Thus far, the role of these biomarkers could only be studied globally but not in a sample-specific manner. To mitigate this, we introduce spongEffects, a novel method that infers subnetworks (or modules) from ceRNA networks and calculates patient- or sample-specific scores related to their regulatory activity. Notably, these module scores can be inferred from gene expression data alone and can thus be applied to cohorts where miRNA expression information is lacking. We show how spongEffects can be used for downstream machine learning tasks such as tumor classification and for identifying subtype-specific regulatory interactions. In a concrete example of breast cancer subtype classification, we prioritize modules impacting the biology of the different subtypes. In summary, spongEffects can perform classification tasks and prioritize ceRNA modules as biomarkers, hence offering insights into the miRNA regulatory landscape from gene expression data alone.

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“…Network pharmacology is an innovative approach that integrates various omics data to visualize the pharmacological action of any drug or formulation from a multi‐component, multi‐target, and multi‐pathway perspective (Nogales et al, 2022; Silverman et al, 2020). This study first analyzed the effect of ethanol solution extract of Withania somnifera (WSEE) on primary cultured neurons to study its effect on neuronal growth, early development, and synaptogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Network pharmacology is an innovative approach that integrates various omics data to visualize the pharmacological action of any drug or formulation from a multi-component, multi-target, and multipathway perspective (Nogales et al, 2022;Silverman et al, 2020).…”

mentioning

confidence: 99%

Unveiling the effect ofWithania somniferaon neuronal cytoarchitecture and synaptogenesis: A combinedin vitroand network pharmacology approach

Mitra

Munni

Dash

et al. 2022

Phytotherapy Research

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Withania somnifera (WS), is known for its remarkable contribution in herbal medicine and Ayurveda, which is therapeutically applied to improve memory and anxiety in patients. However, the pharmacological details of this plant on memory boosting yet remained undefined. This study provides mechanistic insights on the effect of ethanol solution extract of the whole plant of WS (WSEE) on neuritogenesis by combining in vitro and in silico network pharmacology approaches. WSEE promoted significant neuronal growth through early differentiation, axodendritic arborization, and synaptogenesis on primary hippocampal neurons. The network pharmacological study confirmed that the neuritogenic activity is potentially mediated by modulating the neurotrophin signaling pathway, where NRTK1 (TrkA) was revealed as the primary target of WS secondary metabolites. This neurotrophic activity of WSEE was significantly stifled by the presence of TrkA inhibitor, which further confirms the TrkA‐dependent activity of WSEE. In addition, a molecular docking study suggested steroidal lactones present in the WS might act as nerve growth factor (NGF)‐mimetics, activating TrkA by binding to the NGF‐binding domain. As a whole, the findings of the study suggest a significant role of WSEE on neuritogenesis and its potential to function as a therapeutic agent and in drug designing for the prevention and treatment of memory‐related neurological disorders.

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Network pharmacology: curing causal mechanisms instead of treating symptoms

Cited by 459 publications

References 114 publications

Study on Mechanism of Yiqi Yangyin Jiedu Recipe Inhibiting Triple Negative Breast Cancer Growth: A Network Pharmacology and In Vitro Verification

Study on Mechanism of Yiqi Yangyin Jiedu Recipe Inhibiting Triple Negative Breast Cancer Growth: A Network Pharmacology and In Vitro Verification

spongEffects: ceRNA modules offer patient-specific insights into the miRNA regulatory landscape

Unveiling the effect ofWithania somniferaon neuronal cytoarchitecture and synaptogenesis: A combinedin vitroand network pharmacology approach

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