Journal of Integrative and Translational Biomedicine · Sep 7, 2026
Analysis of Senolytics Sophoretin and Dasatinib across Alzheimer's disease and Annulus Fibrosus Degeneration
By Satbhai AS, Kotharkar E
Background: Flavonoid sophoretin (quercetin) exhibits multi-target biological activity, including senolytic-adjunct that complements the effects of senolytic dasatinib. This study evaluates sophoretin inhibitory and molecular binding with cholinesterase, network interactions, and effects in degenerative biological systems. Methods: In vitro inhibition of cholinesterase was assessed by Ellman's method, and in silico molecular docking was performed using AutoDock Vina. Putative molecular targets of sophoretin were predicted using SwissTargetPrediction and intersected with Alzheimer's-associated proteins to identify overlapping targets, which were mapped for protein–protein network interaction and subjected to enrichment analysis. Effects of sophoretin were evaluated using annulus fibrosus tissue treated with a dasatinib–sophoretin cocktail, as a degeneration-sensitive peripheral model. Results: Sophoretin showed concentration-dependent inhibition of cholinesterase, with lower potency than donepezil at low-to-intermediate concentrations but comparable inhibition. Binding affinities were nearly equivalent to donepezil, with sophoretin interaction profile distinguished by a greater contribution of hydrogen bonds/polar contacts, contrasting with donepezil predominantly hydrophobic binding mode. Network analysis identified 25 overlapping targets between sophoretin and Alzheimer's-associated proteins, with significant enrichment in MAPK and PI3K-Akt signaling, amyloid response, and apoptosis regulation. Gene expression analysis of annulus fibrosus tissue following combination treatment revealed 170 differentially expressed genes, indicating broad and bidirectional transcriptional reprogramming. Conclusion: Sophoretin exhibits multi-scale biological activity with Alzheimer's-relevant protein networks and systemic transcriptional responsiveness in a degeneration-sensitive tissue model. These findings support the characterization of sophoretin as a multi-modal bioactive compound with potential relevance across Alzheimer's-associated and broader degenerative pathways, warranting further in vivo validation.