Tricetin, a Dietary Flavonoid, Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer’s Disease by Regulating the PI3K/Akt/mTOR Signaling Pathway

Alzheimer's disease (AD), the most prevalent neurodegenerative disorder among older adults, significantly impairs behavioral and cognitive functions, posing a severe threat to patients' health and quality of life. The Tricetin (TRN), a natural flavonoid found in wheat, pomegranate, and eucalyptus honey, has demonstrated anti-inflammatory, antitumor, and neuroprotective properties. However, its role in the context of AD has not been previously explored. This study investigated the antineuroinflammatory and autophagic protective effects of TRN in lipopolysaccharide (LPS)-induced BV2 cells and _D-galactose/sodium nitrite/aluminum chloride (_D-gal/NaNO₂/AlCl₃)-induced AD mice. The RNA sequencing examined the underlying mechanisms by which TRN ameliorates AD-related pathologies. Our research findings revealed that TRN significantly improved memory and mobility in AD mice, reduced Aβ deposition, and inhibited Tau protein phosphorylation. Furthermore, TRN regulated enzyme activities and reduced pathological markers associated with AD. Moreover, it modulated inflammatory mediators, inhibited the nuclear translocation of NF-κB in LPS-induced BV2 cells, and exerted anti-inflammatory and autophagic protective effects via the PI3K/Akt/mTOR signaling pathway. In conclusion, TRN demonstrated robust neuroprotective effects in vitro and in vivo AD models by regulating the PI3K/Akt/mTOR signaling pathway. These findings highlight its potential as a promising therapeutic agent for treating AD.