Targeting neuroinflammation: Anti-alzheimer’s mechanism of Cassia fistula via in silico approaches

Alzheimer's disease (AD) is a primary factor in neurodegeneration and dementia, with more research linking it to chronic neuroinflammation caused by the excessive activation of intracellular signaling pathways. This study investigates the anti-inflammatory properties of Cassia fistula phytoconstituents on two significant neuroinflammatory targets, SRC kinase and STAT3, using in-silico methodologies. Eleven chemicals identified by LC-MS profiling of methanolic extracts were analyzed using molecular docking utilizing AutoDock Vina v1.2.0. Fucosterol has the highest binding affinity for SRC (-10.3 kcal/mol) and STAT3 (-6.6 kcal/mol). We used Schrödinger's Desmond module to conduct a 100 ns molecular dynamics simulation to assess the stability and interactions of the fucosterol-SRC complex with other molecules. The molecule demonstrated stability in the simulation, exhibiting consistent hydrogen bonding and hydrophobic interactions. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) free energy simulations indicated favorable binding energetics. A DFT analysis demonstrated the electrical characteristics of fucosterol, highlighting a minimal HOMO-LUMO energy gap and an electrophilic potential. Principal Component Analysis (PCA) of the molecular dynamic’s trajectory demonstrated minimal conformational variations, suggesting structural stability of the bound complex. This comprehensive computational investigation reveals fucosterol derived from Cassia fistula as a prospective natural inhibitor of neuroinflammatory signaling in Alzheimer's disease.