Sesame lignans as promising anti-inflammatory agent: Exploring novel therapeutic avenues with in silico and computational approach

Innumerable health-beneficial properties of sesame lignans like sesamol, sesamolin, sesamin and sesaminol make them lucrative agents in the pharmaceutical industry. To specify the mode of action of these phytochemicals, detailed computational physicochemical properties evaluation, and toxicity assessment (using free web servers and databases), as well as binding interactions with physiological inflammatory effectors (such as COX-2, TNF-α , IL-1 β , IL-6) by means of rigid ligand-receptor docking (using software), have been thoroughly investigated. Interestingly, sesame lignans are conformed to have drug-likeness, indicating their efficacy and suitability like established therapeutics. These bioactive lignans possess drug-like attributes and effectively act as ligands in the present in-silico study. The basic pharmacokinetic profile of these compounds has suggested non-polar solvents or delivery systems for them to enhance their bioavailability in physiological systems. However, all the sesame lignans are toxic to the liver cells with a50 % lethal dose in the range of 500-1500 mg/kg. Toxicity study indicated minimum toxicity of lignans to normal cellular milieu, but noticeable cytotoxic effects against several cancerous cell lines suggesting their anti-carcinogenic properties. Finally, the findings of the molecular docking study have depicted a high affinity of these ligands for target proteins, even better than traditional anti-inflammatory drugs-Indomethacin and Ibuprofen. The molecular interactions have represented sesaminol as the most effective and Sesamol as the least potent ligand for target receptor whereas COX-2 seems to be the most vulnerable target. The docking scores varied widely (-4.7 to -11.0 kcal/mol). The present in-silico approach is expected to provide valuable resources for optimizing bioactive molecules as future-generation therapeutics before pre-clinical and clinical studies.