橙皮苷
自噬
氧化应激
神经保护
下调和上调
秀丽隐杆线虫
药理学
化学
生物
细胞生物学
生物化学
医学
细胞凋亡
基因
病理
替代医学
作者
Sandeep Kumar,Parvathaneni Akhila,Kitlangki Suchiang
标识
DOI:10.1016/j.freeradbiomed.2023.10.408
摘要
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 α7nAChR functioning are associated with enhanced amyloid-beta (Aβ) 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-Aβ 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 nerve 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 Aβ-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 Aβ-induced toxicity in C. elegans. Thus, acr-16 mediated autophagy and antioxidation is associated with anti-aging and anti-Aβ effect of hesperidin.
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