RESUMO
BACKGROUND: PPAR-γ has an integrative role in the management of insulin resistance; ligands of this receptor have emerged as potent insulin sensitizers and may modulate proteins involved in the pathogenesis of diabetes mellitus. Hence the present study is aimed to identify PPAR-γ modulators from the plant Cassia glauca and predict the ontology enrichment analysis utilizing various in-silico tools. METHODS: ChEBI database was used to mine the phytoconstituents present in the plant C. glauca, SwissTargetPrediction database was used to identify the targets, and scrutinizing of phytoconstituents modulating PPAR-γ was performed. Autodock4.0 was used to dock phytoconstituent ligands with the target PPAR-γ. Multiple open-source databases and in-silico tools were utilized to predict the drug-likeness characters and predict side effects of the phytoconstituents modulating PPAR-γ and STRING database was used to construct a network between the modulated genes. RESULTS: Twenty-four phytoconstituents were identified from the plant Cassia glauca from which four were found to modulate PPAR-γ, sennoside was predicted to have the greatest drug-likeness score and a significantly less side effect whereas diphenyl sulfone was predicted to show hepatotoxicity with the greatest pharmacological activity of 0.815. [epicatechin-(4beta- > 8)]5-epicatechin showed the lowest binding affinity with target PPAR-γ i.e. -8.6 kcal/mol and possessing a positive drug-likeness score with no side effect data. CONCLUSION: Bioctives were found free from probable side effects leaving out diphenyl sulfone having a prediction of hepatotoxicity, the anti-diabetic property of the plant may be due to the presence of [epicatechin-(4beta- > 8)]5-epicatechin which needs further validation by in-vitro and in-vivo protocols.
RESUMO
BACKGROUND: The present study aimed to evaluate in vitro α-amylase and α-glucosidase inhibitory activity of various extracts of Cassia glauca, predict the binding affinity of multiple phytoconstituents with both enzymes via in silico molecular docking and identify the probably modulated pathways by the lead hit. METHODS: Different extracts of Cassia glauca i.e. acetone, ethanol, and aqueous extracts were evaluated for α-amylase and α-glucosidase inhibitory activity using in vitro method in which starch and 4-Nitrophenyl ß-D-glucopyranoside were used as substrate respectively. Similarly, the docking study was performed using autodock4 to predict the binding affinity of phytoconstituents with α-amylase and α-glucosidase. After docking, ten different poses were obtained for the ligand molecule. Among them, the pose of ligand molecule with the lowest binding energy was visualized in Discovery Studio 2019. RESULTS AND CONCLUSION: Among the multiple extracts, the aqueous extract showed the highest α-amylase (IC50:652.10 ± 20.09) and α-glucosidase (IC50:482.46 ± 8.70) inhibitory activity. Similarly, cassiaoccidentalin B was predicted to have the highest binding affinity with both enzymes. The potency of aqueous extract to inhibit α-amylase and α-glucosidase could be due to multiple water-soluble compounds like saponins, flavonoids, and glycosides.
