Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in aged populations. Aberrant amyloid-beta accumulation is a common pathological feature in AD patients. Dysfunction of autophagy and impairment of &#
x3b1;7nAChR functioning are associated with enhanced amyloid-beta (A&#
x3b2;) accumulation in AD patients. Hesperidin, a flavone glycoside found primarily in citrus species, is known to have anti-inflammatory, antioxidant, and neuroprotective effects. However, the underlying molecular mechanisms of hesperidin as an antiaging and anti-A&#
x3b2; phytochemical were unclear. In this study, we found that hesperidin upregulates the
acr-16 expression level in C. elegans as evidenced by increased GFP-tagged ACR-16 and GFP-tagged
pmyo-3:ACR-16 expression in muscle and ventral cord. Further, hesperidin upregulates the autophagy genes in wild-type N2, evident by increased GFP-tagged LGG-1 foci. However, hesperidin failed to upregulate the autophagy genes level in
acr-16 mutant worms that suggests autophagy activation is mediated through
acr-16. In addition, hesperidin showed antiaging and anti-oxidative effects, as evidenced by positive changes in different markers necessary for health span and lifespan. Additionally, hesperidin could upregulate
acr-16 and autophagy genes (
lgg-1 &
bec-1) and ameliorates A&#
x3b2;-induced toxicity as observed with reduce ROS accumulation, paralysis rate, and enhanced lifespan even in worms AD model CL4176 and CL2006 strain. Our finding suggests that hesperidin significantly enhances oxidative stress resistance, prolongs the lifespan, and protects against A&#
x3b2;-induced toxicity in C. elegans.
acr-16 mediated autophagy and antioxidation is associated with anti-aging and anti-A&#
x3b2; effect of hesperidin.