Network‐based Approaches in Pharmacology

Boezio, Baptiste; Audouze, Karine; Ducrot, Pierre; Taboureau, Olivier

doi:10.1002/minf.201700048

Cited by 281 publications

(178 citation statements)

References 72 publications

(101 reference statements)

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“…The epileptic network is characterized by pathologic, seizure‐generating "foci" embedded in a web of structural and functional connections, resulting in a complex relationship between foci and the surrounding network that drives seizure dynamics . Based on this concept, which also applies to other brain diseases, developing new therapies that act on individual drug targets may be less effective than multitargeted drugs or drug combinations, that is, “network pharmacology” …”

Section: Combination Treatmentmentioning

confidence: 99%

“…268 Based on this concept, which also applies to other brain diseases, developing new therapies that act on individual drug targets may be less effective than multitargeted drugs or drug combinations, that is, "network pharmacology". [271][272][273][274] We recently proposed network pharmacology as a novel strategy for antiepileptogenesis, that is, drug administration during the latent period following an epileptogenic brain insult with the aim of preventing or modifying development of epilepsy. 273,275 Rather than creating new multitargeted drugs, we suggested repurposing clinically established drugs to form rationally chosen drug cocktails for antiepileptogenesis.…”

Section: Combination Treatmentmentioning

confidence: 99%

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Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?

et al. 2020

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Prevention of epilepsy is a great unmet need. Acute central nervous system (CNS) insults such as traumatic brain injury (TBI), cerebrovascular accidents (CVA), and CNS infections account for 15%‐20% of all epilepsy. Following TBI and CVA, there is a latency of days to years before epilepsy develops. This allows treatment to prevent or modify postinjury epilepsy. No such treatment exists. In animal models of acquired epilepsy, a number of medications in clinical use for diverse indications have been shown to have antiepileptogenic or disease‐modifying effects, including medications with excellent side effect profiles. These include atorvastatin, ceftriaxone, losartan, isoflurane, N‐acetylcysteine, and the antiseizure medications levetiracetam, brivaracetam, topiramate, gabapentin, pregabalin, vigabatrin, and eslicarbazepine acetate. In addition, there are preclinical antiepileptogenic data for anakinra, rapamycin, fingolimod, and erythropoietin, although these medications have potential for more serious side effects. However, except for vigabatrin, there have been almost no translation studies to prevent or modify epilepsy using these potentially “repurposable” medications. We may be missing an opportunity to develop preventive treatment for epilepsy by not evaluating these medications clinically. One reason for the lack of translation studies is that the preclinical data for most of these medications are disparate in terms of types of injury, models within different injury type, dosing, injury–treatment initiation latencies, treatment duration, and epilepsy outcome evaluation mode and duration. This makes it difficult to compare the relative strength of antiepileptogenic evidence across the molecules, and difficult to determine which drug(s) would be the best to evaluate clinically. Furthermore, most preclinical antiepileptogenic studies lack information needed for translation, such as dose–blood level relationship, brain target engagement, and dose‐response, and many use treatment parameters that cannot be applied clinically, for example, treatment initiation before or at the time of injury and dosing higher than tolerated human equivalent dosing. Here, we review animal and human antiepileptogenic evidence for these medications. We highlight the gaps in our knowledge for each molecule that need to be filled in order to consider clinical translation, and we suggest a platform of preclinical antiepileptogenesis evaluation of potentially repurposable molecules or their combinations going forward.

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Section: Combination Treatmentmentioning

confidence: 99%

Section: Combination Treatmentmentioning

confidence: 99%

Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?

et al. 2020

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“…The result of network pharmacology is a highly resilient network system with topological interaction (19,29). Therefore, computational prediction with a PPI network and topology analyses reveals the potential interactions among compounds and multiple signaling transduction molecules underlying a disease phenotype (30). According to the algorithm value, 15 key targets associated with RCC were identified in the current study.…”

Section: Discussionmentioning

confidence: 99%

Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway

Zhu

Na²,

Huang³

et al. 2020

Exp Ther Med

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Renal cell carcinoma (RCC) is one of the most common urological malignancies occurring in adult human kidneys worldwide. Recent research on antitumor drugs has focused on plant extracts, a class of compounds that play critical roles in cancer treatment. The present study aimed to investigate the potential antitumor effect of ginkgolic acid (GA) in RCC. Transwell invasion assay, cell counting kit-8 assay and flow cytometry were used to measure cell migration, cell viability and apoptosis, respectively. A network pharmacology approach was applied to identify pathway information, combining molecular docking techniques to screen for key target information. In the present study, GA inhibited the viability and proliferation of RCC cells (786-O and A498), both in vitro and in vivo, via G 1 arrest. GA also reduced RCC cell invasion and migration. In addition, the epidermal growth factor receptor (EGFR) was identified as a critical target protein of GA, which significantly inactivated EGFR signaling in RCC (P<0.05). Collectively, the present study provided evidence that GA exerts its anticancer function by directly targeting the EGFR signaling pathway, revealing the potential of GA therapy for RCC.

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“…Network pharmacology assists in the identification of drug targets, mimics signal pathways for drug and disease interactions, improves clinical outcomes, and reduces laboratory costs. [18] Herb and plant ingredients have positive prospects for the treatment of complex diseases such as ischemic stroke because of the few side effects and multiple targets. [19] We used network pharmacology-related methods to elucidate the therapeutic targets and mechanistic pathways of bezoar for ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Pharmacological Mechanism of Bezoar on Cerebral Ischemic Stroke using a Network Pharmacology Approach

Wang

et al. 2020

Preprint

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Background: Ischemic stroke is a common clinical disease limited by its time window for treatment. In addition to its high mortality rate, only one treatment currently exists for ischemic stroke. Nonetheless, traditional Chinese medicine is often used as a reatment for the disease. Bezoar is a multi-functional drug that has been demonstrated to be effective for the treatment of ischemic stroke. However, its mechanism of action is yet to be fully elucidated. Based on network pharmacology, we explored the potential mechanism of action of bezoar. Symmap and literature data mining methods were used to obtain the target of bezoar. The mechanism of bezoar for the treatment of ischemic 3 stroke was identified and ischemic stroke-related targets were retrieved using DrugBank, Online Mendelian Inheritance in Man, and Therapeutic Target Database. Protein-protein interaction networks were constructed using the Cytoscape plugin, BisoGenet, and analysed by topological methods. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment were carried out via the Database for Annotation, Visualization, and Integrated Discovery server. We obtained 48 potential targets and 3 signalling pathways, including mitogen-activated protein kinase, hypoxia-inducible factor-1, and tumour necrosis factor signalling pathways. The mechanism of action of bezoar on ischemic stroke involves multiple targets and signalling pathways. Our research provides a network pharmacology framework for future Chinese medicinal research.

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Network‐based Approaches in Pharmacology

Cited by 281 publications

References 72 publications

Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?

Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?

Ginkgolic acid inhibits the growth of renal cell carcinoma cells via inactivation of the EGFR signaling pathway

Exploring the Pharmacological Mechanism of Bezoar on Cerebral Ischemic Stroke using a Network Pharmacology Approach

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