Exploring the neuroprotective potential of saponins through the gut microbiota-brain axis: a narrative review of emerging mechanisms and research directions.

Abstract

Neurodegenerative diseases are defined as progressive and irreversible disorders involving the degeneration of neurons in the brain, giving rise to both cognitive deterioration and motor dysfunction. Diseases such as Alzheimer's, Parkinson's, and Huntington's pose major public health challenges, particularly in aging populations, and are driven by complex mechanisms including oxidative stress, neuroinflammation, and abnormal protein aggregation. Recent evidence suggests that alterations in gut microbiota composition are closely linked to the onset and progression of these disorders. Saponins have been reported to modulate gut microbiota composition and preclinical studies indicate that certain saponins may exert neuroprotective actions in specific models of neurodegeneration. This review summarizes and interprets the emerging, preliminary role of saponins in modulating pathways implicated in neurodegeneration, with a particular focus on their capacity to influence the gut microbiota-brain axis. Specifically, we summarize scientific evidence on how the structural features of saponins shape gut microbial composition and activity, thereby influencing their potential to modulate the development and progression of neurodegenerative disorders. Microbial metabolites, neuroinflammatory cascades, and redox balance represent key pathways potentially influenced by saponins in preclinical contexts, 2 central drivers of neurodegenerative progression. This review also highlights the preliminary nature of current evidence on these potential mechanisms and discusses major knowledge gaps, including saponin toxicity and the need for clinical studies before meaningful translation.