SHIWANI CHAHAL, NITU SAINI, POOJA RIDHAL, RENU KUMARI AND PRIYANKA SIWACH*
Department of Biotechnology, Chaudhary Devi Lal University, Sirsa-125 055 (Haryana), India *(e-mail: priyankasiwach@cdlu.ac.in; Mobile: 94669 15002)
(Received: July 15, 2024; Accepted: September 3, 2024)
ABSTRACT
Overproduction of TNF-α, a key initiator in the inflammatory signalling cascade, can lead to several diseases. Most of commercially available TNF- inhibitors have significant risks. To find safe alternatives, the present study was undertaken to investigate the anti-inflammatory potential of flavonoids and phenolic compounds from Terminalia arjuna, an important medicinal plant from Indian sub-continent. Fifteen ligands were selected against TNF-α (PDB ID: 2AZ5), with its co-crystal ligand (307) used as a positive control. Thirteen ligands that adhered to Lipinski’s rule of five, with 0/1 violations, were subjected to ADMET profiling. Of these, eight ligands with high GI absorption rates and minimal or non-toxic behaviour were taken forward for molecular docking studies. Post-docking analysis, conducted with AutoDock 4.2 and BIOVIA Discovery Studio, revealed that (-)-Epicatechin (-6.8 kcal/mol) exhibited the most stable binding affinity, with a greater number of hydrogen bonds within the active region of the target protein compared to the positive control (-5.6 kcal/mol). These findings suggest the potential of (-)-Epicatechin as an effective TNF-α inhibitor paving the way for further research and development in anti-inflammatory therapies.
Key words: Terminalia arjuna, TNF-α, inflammation, ADMET, molecular docking