The multi-protein targeting potential of bioactive syringin in inflammatory diseases: using molecular modelling and in-silico analysis of regulatory elements.

Inflammation plays a crucial role in the onset or progression of a variety of acute and chronic diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) are the only available FDA-approved therapy. The therapeutic outcome of NSAIDs is still finite due to off-target effects and extreme side effects on other vital organs. Bioactive syringin has been manifested to hold anti-osteoporosis, cardiac hypertrophy, alter autophagy, anti-cancer, neuro-preventive effects, etc. However, its multi-protein targeting potential in inflammation mostly remains unexplored. In the present work, we have checked the multi-protein targeting potential of bioactive glycoside syringin in inflammatory diseases. Based on the binding score of protein-ligand complexes, glycoside syringin scored greater than -7 kcal/mol against 12 inflammatory proteins. Our molecular dynamic simulation study (200 ns) confirmed that bioactive syringin remained inside the binding cavity of inflammatory proteins (JAK1, TYK2, and COX1) in a stable conformation. Further, our co-expression analysis suggests that these genes play an essential role in multiple pathways and are regulated by multiple miRNAs. Our study demonstrates that bioactive glycoside syringin might be a multi-protein targeting potential against inflammatory diseases and could be further investigated utilizing different preclinical approaches.Communicated by Ramaswamy H. Sarma.

Immunomodulatory potential of bioactive glycoside syringin: a network pharmacology and molecular modeling approach.

Many diseases, such as rheumatoid arthritis, neurodegenerative disease, lupus, autoimmune disease, and cancer, are described by chronic inflammation following tissue damage. Anti-inflammatory drugs like non-steroidal anti-inflammatory drugs and other steroids cause many side effects and generally need careful consideration and monitoring during usage. In recent years, a significant interest in plant-derived approaches has been warranted. The bioactive glycoside syringin might be one of the effective immunomodulatory agents. However, its immunomodulatory potential needs to be better known. In this study, we evaluated the immunomodulatory potential of syringin using network pharmacology, molecular docking, and molecular dynamics simulation-based approaches. First, we applied the GeneCards and OMIM databases to acquire the immunomodulatory agents. Then, the STRING database was utilized to get the hub genes. Interaction analysis and molecular docking described strong binding of the active site of immunomodulatory proteins with the bioactive syringin. Molecular dynamics simulations (200 ns) showed a very stable interaction of syringin with the immunomodulatory protein. Further, the optimized structure and molecular electrostatic potential of the syringin were calculated by a density-functional theory utilizing basis levels of B3LYP/6-31. Syringin investigated in this study holds the required drug-likeness characteristics and follows Lipinski's rule of five. However, quantum-chemical estimations show the syringin has potent reactivity, demonstrating a lower energy gap. Furthermore, the gap between ELUMO and EHOMO was low, suggesting the excellent affinity of syringin towards the immunomodulatory proteins. The present study shows that syringin might be an effective immunomodulatory agent and can be further explored using different experimental methods.Communicated by Ramaswamy H. Sarma.