The anti-seizure potential of cysteine leukotriene receptor antagonists: A systematic review of animal studies.

BACKGROUND: Emerging literature has suggested the antiepileptic activity of cysteine leukotriene receptor (CysLTR) antagonists in experimental animals of epilepsy. Leukotrienes are substances that cause inflammation and affect brain activity, blood flow, oxidation, and inflammation in the brain. These processes are related to epilepsy and its complications. CysLTR antagonists are drugs that prevent leukotrienes from working. They may be useful for treating epilepsy, especially for people who do not respond to other drugs. Therefore, the current study aims to systematically review the potential anti-seizure effect of CysLTR antagonists in experimental studies. METHOD: We systematically reviewed the online databases using online databases such as Google Scholar, science direct, and PubMed until December 2022 to identify experimental studies assessing the anti-seizure activity of CysLTR antagonists. The Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) was used to evaluate the risk of bias (RoB) of the included studies. RESULTS: Initially we identified 3823 studies. After screening using inclusion and exclusion criteria, 8 studies were finally included in the current study. All included studies, reported that CysLTR antagonists reduced the intensity of seizures in animal models of epilepsy. CONCLUSION: In conclusion, CysLTR antagonists could be a potential therapeutic approach for the treatment of epilepsy. However, further preclinical and clinical studies are required to confirm their efficacy, safety, and mechanism of anti-seizure activity.

Network pharmacology and molecular docking study-based approach to explore mechanism of benzimidazole-based anthelmintics for the treatment of lung cancer.

Emerging studies have reported the potential anticancer activity of benzimidazole-based anthelmintics (BBA) against lung cancer (LC). However, mechanism underlying the anticancer activity of BBA is unclear. Therefore, in the current study, network pharmacology and molecular docking-based approach were used to explore the potential molecular mechanism for the treatment of LC. The potential targets for BBA were obtained from multiple databases including SwissTargetPrediction, Drug Bank, Therapeutic Target Database, and Comparative Toxicogenomics Database while LC targets were collected from DisGeNet gene discovery platform, Integrated Genomic Database of NSCLC, Catalogue of Somatic Mutations in Cancer and Online Mendelian Inheritance in Man database. Protein-protein interaction (PPI) diagram of common targets was constructed using STRING online platform. Topological analysis was performed using Cytoscape and gene enrichment analysis was conducted using FunRich software. Highest degree targets were then confirmed using molecular docking and molecular dynamics simulations. The BBA were prioritized according to their S scores, with ricobendazole ranking highest followed by flubendazole, fenbendazole, mebendazole, triclabendazole, albendazole, oxibendazole, parbendazole, thiabendazole and oxfendazole. The potential targets of BBA identified using topological analysis and molecular docking were found to be CCND1 (cyclin D1), EGFR (Epidermal Growth Factor Receptor), ERBB2 (Erb-B2 Receptor Tyrosine Kinase 2/CD340), PTGS2 (Prostaglandin-endoperoxide synthase 2), and SRC (Proto-oncogene tyrosine-protein kinase). Furthermore, molecular dynamics confirmed that CCND1 and EGFR are the potential targets of ricobendazole for the treatment of LC. BBA can be further explored as a therapeutic strategy for the treatment of lung cancer under in vitro and in vivo studies.Communicated by Ramaswamy H. Sarma.

Network pharmacology and molecular docking analysis on potential molecular targets and mechanism of action of BRAF inhibitors for application in wound healing.

Topical application of BRAF inhibitors has been shown to accelerate wound healing in murine models, which can be extrapolated into clinical applications. The aim of the study was to identify suitable pharmacological targets of BRAF inhibitors and elucidate their mechanisms of action for therapeutic applicability in wound healing, by employing bioinformatics tools including network pharmacology and molecular docking. The potential targets for BRAF inhibitors were obtained from SwissTargetPrediction, DrugBank, CTD, Therapeutic Target Database, and Binding Database. Targets of wound healing were obtained using online databases DisGeNET and OMIM (Online Mendelian Inheritance in Man). Common targets were found by using the online GeneVenn tool. Common targets were then imported to STRING to construct interaction networks. Topological parameters were assessed using Cytoscape and core targets were identified. FunRich was employed to uncover the signaling pathways, cellular components, molecular functions, and biological processes in which the core targets participate. Finally, molecular docking was performed using MOE software. Key targets for the therapeutic application of BRAF inhibitors for wound healing are peroxisome proliferator-activated receptor γ, matrix metalloproteinase 9, AKT serine/threonine kinase 1, mammalian target of rapamycin, and Ki-ras2 Kirsten rat sarcoma viral oncogene homolog. The most potent BRAF inhibitors that can be exploited for their paradoxical activity for wound healing applications are Encorafenib and Dabrafenib. By using network pharmacology and molecular docking, it can be predicted that the paradoxical activity of BRAF inhibitors can be used for their potential application in wound healing.