β-Sitosterol as a nutrient-derived steroidal scaffold in ageing and neurodegenerative disorders: Molecular mechanisms and systems biology insights

Ageing is a major driver of neurodegenerative and neurobehavioral disorders, characterized by interconnected processes such as neuroinflammation, oxidative stress, mitochondrial dysfunction. β-Sitosterol (BS), a diet-derived phytosterol with a steroidal scaffold structurally analogous to cholesterol, has emerged as a multitarget bioactive capable of modulating these ageing-associated pathways. Using a systems biology and network pharmacology framework, this review highlights BS interactions with key molecular targets, including glucocorticoid and estrogen receptors, AKT1, MAPK1, and inflammatory mediators. Mechanistically, it integrates endocrine, neuroimmune, and synaptic signaling while influencing AMPK-SIRT1 pathways and the gut-brain axis.