Ezaouine Adbelkarim, Salam Mohamed Rida, Nouadi Badreddine, Anachad Oumaima, Messal Mariame El, Chegdani Fatima, Bennis Faïza
Immunology and Biodiversity laboratory, Faculty of Sciences Aïn Chock, Hassan II University of Casablanca, Casablanca, Morocco.
Bioinform Biol Insights. 2022 Aug 4;16:11779322221115665. doi: 10.1177/11779322221115665. eCollection 2022.
Inflammatory bowel diseases are caused by an abnormal reaction of the immune system, which becomes hyperactive because the mechanisms responsible for regulating it get out of control. For an effective immune response, many proinflammatory cytokines are secreted, particularly interleukin-6 (IL-6) keystone cytokine inflammation. Many synthetic and natural compounds targeting IL-6 have been studied. The genus of the Lamiaceae family is generally known for its many virtues, in particular anti-inflammatory properties. However, the mechanism of action is unclear. This study aims to predict the impact of characterized bioactive molecules of Moroccan in the potential control of inflammatory response mediated by IL-6 cytokine. A list of 9 previously characterized natural compounds of was compiled, and a list of 6 potential protein targets involved in intestinal inflammation was made. The 2 lists of natural compound-target proteins were analyzed by the STITCH software (http://stitch.embl.de/) to develop protein-compound and protein-protein interaction networks (PPINs). An ontological enrichment (GO) analysis was performed by the Clue GO plugin to evaluate the PPIN generated by STITCH; finally, the molecular docking to predict the mode underlying the anti-inflammatory effects. STITCH results revealed direct and indirect interactions of chemical compounds with a key protein target IL-6. The array results by ClueGO showed that most compounds involved in the regulation of several biological processes related to IL-6 such as inflammation apoptosis, cell differentiation, and metabolic regulation. The targets directly related to IL-6 have been used for molecular docking. Quercetin, catechin, and gallic acid have a strong affinity with the IL-6 receptor (respectively -7.1; -6.1; -5.3). This study strongly suggests that the bioactive compounds of could constitute a new therapeutic alternative in the treatment of diseases related to IL-6. However, to validate the results obtained in this work, it is necessary to explore the mechanism of action of potential bioactive molecules by experimentation.
炎症性肠病是由免疫系统的异常反应引起的，免疫系统会变得过度活跃，因为负责调节它的机制失控了。为了产生有效的免疫反应，会分泌许多促炎细胞因子，特别是白细胞介素-6（IL-6）这种关键的细胞因子。许多针对IL-6的合成和天然化合物都已被研究。唇形科植物通常因其诸多优点而闻名，尤其是具有抗炎特性。然而，其作用机制尚不清楚。本研究旨在预测摩洛哥唇形科植物中已鉴定的生物活性分子对由IL-6细胞因子介导的炎症反应的潜在控制作用。编制了一份9种先前已鉴定的唇形科植物天然化合物的清单，并列出了6个参与肠道炎症的潜在蛋白质靶点。通过STITCH软件（http://stitch.embl.de/）分析天然化合物-靶蛋白的这两个清单，以构建蛋白质-化合物和蛋白质-蛋白质相互作用网络（PPINs）。通过Clue GO插件进行本体富集（GO）分析，以评估由STITCH生成的PPIN；最后，进行分子对接以预测抗炎作用的潜在模式。STITCH结果揭示了化学化合物与关键蛋白靶点IL-6的直接和间接相互作用。ClueGO的阵列结果表明，大多数化合物参与了与IL-6相关的几个生物学过程的调节，如炎症凋亡、细胞分化和代谢调节。与IL-6直接相关的靶点已用于分子对接。槲皮素、儿茶素和没食子酸与IL-6受体具有很强的亲和力（分别为-7.1；-6.1；-5.3）。本研究强烈表明，唇形科植物的生物活性化合物可能构成治疗与IL-6相关疾病的新治疗选择。然而，为了验证本研究中获得的结果，有必要通过实验探索潜在生物活性分子的作用机制。
