Geniposide effectively safeguards HT22 cells against Aβ-induced damage by activating mitophagy via the PINK1/Parkin signaling pathway

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the significant involvement of amyloid-beta (A beta) peptide in its pathogenesis. Geniposide, derived from the versatile medicinal of Gardenia jasminoides , is one of the active compounds studied extensively. The objective was to explore the impact of geniposide on A beta 25-35-induced damage in HT22 cells, specifically focusing on its modulation of PINK1/Parkinmediated mitophagy. In our investigation, geniposide exhibited remarkable restorative effects by enhancing cell viability and preserving the mitochondrial membrane potential. Moreover, it effectively reduced and mitigated the oxidative stress and apoptosis rates induced by A beta 25-35 . Notably, geniposide exhibited the capacity to enhance autophagic flux, upregulate LC3II and Beclin-1 expression, and downregulate the expression of p62. Furthermore, geniposide positively influenced the expression of PINK1 and Parkin proteins, with molecular docking substantiating a strong interaction between geniposide and PINK1/Parkin proteins. Intriguingly, the beneficial outcomes of geniposide on alleviating the pronounced apoptosis rates, the overproduction of reactive oxygen species, and diminished the PINK1 and Parkin expression induced by A beta 25-35 were compromised by the mitophagy inhibitor cyclosporine A (CsA). Collectively, these findings suggested that geniposide potentially shields HT22 cells against neurodegenerative damage triggered by A beta 25-35 through the activation of mitophagy. The insights contribute valuable references to the defensive consequences against neurological damage of geniposide, thereby highlighting its potential as a therapeutic intervention in AD.