Countering oxysterol-driven neurodegeneration: diosgenin as a privileged steroidal scaffold for novel Alzheimer’s disease therapeutics

Abstract

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β accumulation, tau pathology, oxidative stress, neuroinflammation, and lipid dysregulation. The limited success of single-target therapeutics has shifted attention toward multi-target phytotherapeutics with pleiotropic neuroprotective properties. Diosgenin, a steroidal sapogenin structurally related to cholesterol-derived oxysterols, has emerged as a promising candidate owing to its antioxidant, anti-inflammatory, and neurorestorative activities. This mini-review highlights diosgenin as a structural antagonist to 7-ketocholesterol (7-KC), emphasizing its ability to modulate oxidative stress, amyloidogenesis, neuronal survival, and membrane stability. Additionally, translational strategies including semi-synthetic modification and nanocarrier-mediated brain delivery are discussed as future therapeutic avenues for AD management.

Keywords: Alzheimer’s disease, diosgenin, 7-ketocholesterol, neuroprotection, steroidal sapogenins