In Silico Prediction of the Bioactive Profile and Metabolites of Satureja nepeta in Diseases Related to the Excessive Production of Interleukin-6

Abstract

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 Satureja 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 Satureja nepeta in the potential control of inflammatory response mediated by IL-6 cytokine. A list of 9 previously characterized natural compounds of S. nepeta 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 S. nepeta 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 S. nepeta 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.

Datura stramonium Flowers as a Potential Natural Resource of Bioactive Molecules: Identification of Anti-Inflammatory Agents and Molecular Docking Analysis

“…This interaction involved one conventional hydrogen bond, one Van der Waals interaction and one Pi-sigma bond in the active site ( Figure 6 ). IL-6, also known as interferon β2, is a key cytokine in the regulation of inflammation and is produced in response to infections [ 53 ]. It is also involved in the pathogenesis of rheumatoid arthritis [ 54 ].…”

“…It was previously shown that quercetin, catechin, and gallic acid from Satureja nepeta extract exhibited a strong affinity with IL-6R with binding energy values of −7.1, −6.1, and −5.3 kcal/mol, respectively. It was suggested that the interaction with the active site of IL-6R could be a suitable mechanism for the inhibition of IL-6 by S. nepeta polyphenols [ 53 ]. It was recently noticed that genistein showed an excellent binding energy (−10.59 kcal/mol) with IL-6/IL-6Rα of the STAT3 pathway and could therefore inhibit the IL-6/STAT3 pathway by blocking the interaction of IL-6 with IL-6R [ 55 ].…”

Potentiality of Resveratrol in Mitigating Exercise-Induced Inflammation - A Bioinformatic Study on Interleukin-6 (IL-6) in Athletes

“…In response to this emerging challenge, the scientific community has turned to innovative approaches, particularly bioinformatic applications, to unravel the complex interplay between exercise, IL-6, and inflammation. Bioinformatics leverages computational tools and techniques to analyze vast amounts of biological data, facilitating a deeper understanding of molecular pathways and interactions [29,30]. Researchers are now using bioinformatics to explore the intricate mechanisms through which heavy exercise influences IL-6 levels and subsequent inflammatory responses [29,31].…”

“…Bioinformatics leverages computational tools and techniques to analyze vast amounts of biological data, facilitating a deeper understanding of molecular pathways and interactions [29,30]. Researchers are now using bioinformatics to explore the intricate mechanisms through which heavy exercise influences IL-6 levels and subsequent inflammatory responses [29,31]. This multidisciplinary approach enables the identification of potential targets for intervention, paving the way for the development of anti-inflammatory drugs tailored to mitigate the negative consequences of intense physical activity.…”

Phenolic Compounds of Therapeutic Interest in Neuroprotection

“…On the other hand, Adbelkarim et al [59] performed an in-silico analysis of phenolic compounds derived from Moroccan Satureja nepeta, such as quercetin, catechin, and gallic acid, which have a high affinity for the IL-6 receptor, an interleukin that is related to inflammation, apoptosis, and cell differentiation. In addition, it has been shown to have an important role in neurodegenerative diseases [60][61][62].…”