基于数据挖掘、网络药理学和对接分析,探索沙特阿拉伯植物抗癫痫的多基因调控分子机制。
Exploring the multi-gene regulatory molecular mechanism of Saudi Arabian flora against epilepsy based on data mining, network pharmacology and docking analysis.
发表日期:2023 Sep
作者:
Faez Falah Alshehri, Fuad M Alzahrani, Abdulaziz Alkhoshaiban, Zafer Saad Al Shehri
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
癫痫是一种慢性神经系统疾病,以反复发作的癫痫样发作为特征,显著影响沙特阿拉伯各年龄段的人口。全球癫痫的患病率约为每千人6.38,而阿拉伯地区的活动癫痫患病率中位数为每千人4.4。然而,超过75%的患者没有接受治疗。因此,开发疗效和安全性更高的治疗策略对于改善癫痫患者的生存率至关重要。本研究结合网络药理学和生物信息学方法,探索沙特阿拉伯本土植物,包括草莓茄(Solanum incanum)、刺灵豆(Abrus precatorius)、印度人参(Withania somnifera)和苦楝(Azadirachta indica)在癫痫治疗中的潜在分子机制。在初步阶段,从科学文献和开放源数据库中收集了与本土植物的活性成分以及这些植物和癫痫的相关靶基因有关的数据。然后对这些数据进行分析,以确定植物和卵巢癌之间的共同靶标。基于这些共同靶标,利用STRING数据库构建了蛋白质相互作用(PPI)网络,然后将其整合到Cytoscape软件中,以根据其连接程度鉴定中心基因。最后,通过Cytoscape绘制了描绘化合物和重叠基因之间关联的相互作用网络,以研究这些活性成分在卵巢癌中的潜在网络药理学意义。在此基础上,构建了化合物-靶蛋白-通路网络,揭示了abrectorin、genistin、(+)-catechin、precatorine、(+)-ascorbic acid、licoflavanone、skrofulein、stigmasterone、5,7-Dihydroxy-4'-methoxy-8,3'-di-C-prenylflavanone这些化合物可能可用作靶向TNF和TP53蛋白的抗癫痫治疗药物。此外,分子对接实验证实了这些化合物与靶蛋白的结合亲和力,表明预测化合物在结合位点具有较强的稳定性。本研究为进一步的深入研究奠定了理论和实验基础,并为活性化合物在抗癫痫药物开发中的战略应用建立了实际方法。© 2023作者
Epilepsy is a chronic neurological disorder marked by recurrent seizures, significantly affecting the population in Saudi Arabia across all age demographics. The global prevalence of active epilepsy is around 6.38/1,000 persons and in the Arabian region, the median prevalence of active epilepsy is 4.4/1,000 persons. However, over 75% of individuals are untreated. Consequently, the development of therapeutic strategies with increased efficacy and safety profiles is essential to improve the survival rate among epilepsy patients. The current study integrates network pharmacology along with Bioinformatics approaches to explore the potential molecular mechanisms of local flora of Saudi Arabia including Solanum incanum, Abrus precatorius, Withania somnifera, and Azadirachta indica in epilepsy treatment. In the preliminary phase, data related to the bioactive components of the local plants and the associated target genes of both these plants and epilepsy were gathered from scientific literature and open-source databases. This data was then analyzed to identify common targets between the plants and ovarian cancer. Based on these common targets, a protein-protein interaction (PPI) network was constructed utilizing the STRING database, which was subsequently incorporated into the Cytoscape software for identification of hub genes based on their degree of connectivity. Lastly, an interplay network depicting the associations between the compounds and the overlapping genes was formulated via Cytoscape, to study the potential network pharmacology implications of these active compounds in relation to ovarian cancer. Following that, a compound-target protein-pathway network was constructed which uncovered that namely abrectorin, genistin, (+)-catechin, precatorine, (+)-ascorbic acid, licoflavanone, skrofulein, stigmasterone, 5,7-Dihydroxy-4'-methoxy-8,3'-di-C-prenylflavanone could potentially be used as antagonists for the therapeutic management of epilepsy by targeting TNF and TP53 proteins. Furthermore, the implementation of molecular docking reinforces the binding affinity of the compound, indicating a robust stability of the forecasted compounds at the docked site. This research lays both a theoretical and experimental groundwork for more profound investigations and establishes a practical method for the strategic employment of active compounds in the development of anti-epileptic therapeutics.© 2023 The Authors.