Aqueous Extract of Lycium ruthenicum Murray Attenuates Neuroinflammation in C57BL/6J Mice Induced by High-Fat and High-Fructose Diet Through Regulating Gut Microbiota and Bile Acid Metabolism

The aqueous extract of <i>Lycium ruthenicum</i> Murray (LRE) could attenuate neuroinflammation in mice induced by a high-fat and high-fructose diet (HFFD). Moreover, LRE could adjust bile acid (BA) metabolism and the gut microbiota. Behavioral tests revealed that LRE prevented HFFD-induced cognitive deficits. The treatment of LRE resulted in a decreased expression of inflammation-related mRNA of TNF-α, IL-6, and IL-1β in the cerebral cortex and hippocampus. Furthermore, LRE ameliorated gut microbiota disorder caused by HFFD by markedly elevating the relative abundances of <i>Streptococcus</i> and probiotics such as <i>Lactococcus</i>. Concurrently, it reduced the relative abundances of <i>Helicobacter</i> and <i>Clostridium_XIVa.</i> The levels of tauroursodeoxycholic acid, known for its neuroprotective property, and taurocholic acid, recognized as an anti-inflammatory agent, were significantly enhanced in the hippocampus and cerebral cortex due to the treatment with LRE. In a word, LRE might have the potential to alleviate HFFD-induced cognitive dysfunction by modulating intestinal microbiota and promoting the synthesis of neuroprotective BAs.