The anti-aging and anti-Alzheimer's disease potential of kinsenoside prepared from Anoectochilus roxburghii

Anoectochilus roxburghii is a high-value plant resource for nutraceutical efficacy and medicinal applications, among which kinsenoside is recognized as the main bioactive glycoside. However, the anti-aging and anti-Alzheimer's disease (AD) activities of kinsenoside have long been neglected. The objective of this study was to investigate the influences of kinsenoside on aging and amyloid-β (Aβ) proteotoxicity and underlying molecular mechanisms in Caenorhabditis elegans (C. elegans). Kinsenoside (50 μM) could significantly prolong the mean lifespan of C. elegans by 26.3 %. Moreover, it improved the physiological functions, stress resistance and in vivo antioxidant activities of C. elegans. Further studies indicated that kinsenoside upregulated the mRNA expression levels of aging-associated genes including sir-2.1, hsp-16.2, sek-1, skn-1, sod-3, hsf-1, gst-4. The genetic studies and molecular docking studies supported that SKN-1 and HSF-1 transcription factors were requirements for the kinsenoside-mediated longevity. Furthermore, kinsenoside could exert a protective effect on Aβ-induced proteotoxicity by regulating stress-responsive and autophagy-related genes in C. elegans CL4176. The results sheds light on the bioactive properties and pharmaceutical potential of kinsenoside including anti-aging and anti-AD, broadening the prospects of kinsenoside for industrial applications.