Regulation of Interleukin 2, Proto-Oncogene c-Fos and Poly (ADP-Ribose) Glycohydrolase Genomic Expression by Rosmarinic Acid in Attenuation of Diabetes and Associated Complications

Abstract

Background: Exploration of multi-targeted and therapeutic approaches is critically needed to obviate the therapeutic berries for the treatment of acute or chronic diseases. Interleukin 2 (IL2), Proto-oncogene c-Fos (FOS) and poly (ADP-ribose) glycohydrolase (PARG) are considerable bioregulators in diabetes and associated complications via blocking pancreatic β cells destruction, increasing insulin sensitivity and rate of glycolysis, electron transport, and adenosine triphosphate (ATP) formation. Taking these factors into consideration, the present study is associated to explore the multi-mechanistic and therapeutic effects of rosmarinic acid for applications of diabetes and associated complications. Methods: Network biology and poly-pharmacology studies were conducted for the evaluation of the therapeutic effect of rosmarinic acid in the alleviation of diabetes and associated complication. Gene ontology analysis was performed to determine the pathophysiological targets genes and rosmarinic acid in diabetes. In-silico docking analysis was performed to determine the molecular interaction and binding ability of proteins with rosmarinic acid to explore its biomolecular approaches involved in diabetes. Results: The outcome of the study showed that rosmarinic acid exhibits a multi-targeted and therapeutic effect in the alleviation of diabetes via regulation of hyperinsulinism, insulin resistance, lipoatrophic diabetes mellitus, lipoatrophy, liver failure, liver cirrhosis, oxidative and inflammatory stress, etc., it regulates the expression of genes such as IL2, lymphocyte-specific protein tyrosine kinase (LCK), an inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB), FOS, C-C motif chemokine receptor 3 (CCR3), Protein C Receptor (PROCR) and PARG that are involved in the pathogenesis of diabetes and associated complication. In-silico docking outcomes revealed that rosmarinic acid is the most potent active therapeutic agent that significantly interacts with IL2 protein and may regulate interleukins-associated inflammatory damage. Conclusions: It can be demonstrated that rosmarinic acid reduces oxidative and inflammatory damage, hyperinsulinism, insulin resistance, lipoatrophic diabetes mellitus, lipoatrophy, etc., via regulation of IL2, FOS and PARG genomic expression and attenuates diabetes and associated complications.