Cassia glauca is reported for anti-diabetic action and is also used as an ethnomedicine.

Sinapic acid is a hydroxycinnamic acid widespread in the plant kingdom, known to be a potent anti-oxidant used for the treatment of cancer, infections, oxidative stress, and inflammation. However, the mode of action for its chemotherapeutic properties has yet not been unleashed. Hence, we aimed to identify potential targets to propose a possible molecular mechanism for sinapic acid against breast cancer. We utilized multiple system biology tools and databases like DisGeNET, DIGEP-Pred, Cytoscape, STRING, AutoDock 4.2, AutoDock vina, Schrodinger, and gromacs to predict a probable molecular mechanism for sinapic acid against breast cancer. Targets for the disease breast cancer, were identified via DisGeNET database which were further matched with proteins predicted to be modulated by sinapic acid. In addition, KEGG pathway analysis was used to identify pathways; a protein-pathway network was constructed via Cytoscape. Molecular docking was performed using three different algorithms followed by molecular dynamic simulations and MMPBSA analysis. Moreover, cluster analysis and gene ontology (GO) analysis were performed. A total of 6776 targets were identified for breast cancer; 95.38% of genes predicted to be modulated by sinapic acid were common with genes of breast cancer. The ‘Pathways in cancer’ was predicted to be modulated by most umber of proteins. Further,PRKCA,CASP8, andCTNNB1were predicted to be the top 3 hub genes. In addition, molecular docking studies revealedCYP3A4,CYP1A1, andSIRT1to be the lead proteins identified from AutoDock 4.2, AutoDock Vina, and Schrodinger suite Glide respectively. Molecular dynamic simulation and MMPBSA were performed for the complex of sinapic acid with above mentioned proteins which revealed a stable complex throughout simulation. The predictions revealed that the mechanism of sinapic acid in breast cancer may be due to regulation of multiple proteins likeCTNNB1,PRKCA,CASP8,SIRT1, and cytochrome enzymes (CYP1A1&CYP3A4); the majorly regulated pathway was predicted to be ‘Pathways in cancer’. This indicates the rationale for sinapic acid to be used in the treatment of breast cancer. However, these are predictions and need to be validated and looked upon in-depth to confirm the exact mechanism of sinapic acid in the treatment of breast cancer; this is future scope as well as a drawback of the current study.

Previously, barosmin has been demonstrated to possess anti-diabetic action. However, its effect to inhibit α-amylase and α-glucosidase, including glucose utilization efficacy, has yet to be revealed. Hence, the current study attempted to assess the efficiency of barosmin in inhibiting the α-amylase, α -glucosidase, and dipeptidyl peptidase 4 enzymes, including glucose uptake efficacy. Molecular docking and simulation were performed using AutoDock Vina and Gromacs respectively followed by gene ontology analysis using the database for annotation, visualization, and integrated discovery. Further, in vitro enzyme inhibitory activities and glucose uptake assay were performed in L6 cell lines. Density functional theory analysis detailed mechanistic insights into the crucial interaction sites of barosmin of which the electron-dense region was prone to nucleophilic attack (O-atoms) whereas hydroxyl groups (-OH) showed affinity for electrophilic attacks. Barosmin showed good binding affinity with α-amylase (-9.2 kcal/mol), α-glucosidase (-10.7 kcal/mol), and dipeptidyl peptidase 4 (-10.0 kcal/mol). Barosmin formed stable nonbonded contacts with active site residues of aforementioned enzymes throughout 200 ns molecular dynamics simulation. Further, it regulated pathway concerned with glucose homeostasis i.e. tumor necrosis factor signaling pathway. In addition, barosmin showed α-amylase (IC₅₀= 95.77 ± 23.33 µg/mL), α-glucosidase (IC₅₀= 68.13 ± 2.95 µg/mL), and dipeptidyl peptidase 4 (IC₅₀= 13.27 ± 1.99 µg/mL) inhibitory activities including glucose uptake efficacy in L6 cell lines (EC₅₀= 12.46 ± 0.90 µg/mL) in the presence of insulin. This study presents the efficacy of the barosmin to inhibit α-amylase and α-glucosidase and glucose uptake efficacy in L6 cell lines via the use of multiple system biology tools and in vitro techniques.Communicated by Ramaswamy H. Sarma.