Flavonoids from Shiliangcha (<i>Chimonanthus salicifolius</i>) Alleviate Brain Aging in <scp>d</scp>-Galactose-Induced Senescent Mice through Gut Microbiota

The leaves of Shiliangcha (an alternative tea, <i>Chimonanthus salicifolius</i>), a perennial bush cultivated in Lishui, Zhejiang, have been used for thousands of years by the She ethnic group as an herb and tea. <i>Chimonanthus salicifolius</i> flavonoids (CsFE) have exhibited remarkable antiaging properties. Therefore, we established a d-galactose (d_Gal)-induced aging mouse model to investigate the effect of CsFE on the central nervous system (CNS) of aging hosts. Supplementation with CsFE effectively alleviated symptoms of aging in mice, including weight loss, declining learning and memory capacity, blood-brain barrier (BBB) integrity, release of pro-inflammatory cytokines, oxidative stress, neuroinflammation, and microglia activation. Additionally, CsFE alleviated cognitive deficits by interfering with synaptic plasticity-associated protein levels, altering neuronal excitability, and affecting intracellular neurotransmitters glutamate (Glu) and γ-aminobutyric acid (GABA) release. Furthermore, CsFE supplementation modulated gut microbiota composition by enriching probiotics <i>Akkermansia</i>, <i>Muribaculaceae</i>, <i>Lactobacillus</i>, and <i>Lachnospiraceae</i>, promoting the production of short-chain fatty acids (SCFAs). Therefore, this study suggested that CsFE has the potential to resist brain aging through intervention of the microbiota-gut-brain axis (GBA), which provides a theoretical basis for the development of natural drugs and dietary supplements for antiaging.