Chlorogenic Acid Ameliorates High-Fat and High-Fructose Diet-Induced Cognitive Impairment via Mediating the Microbiota–Gut–Brain Axis

Abstract

Chlorogenic acid (CGA) displays cognition-improving properties, but the underlying mechanisms remain unclear. Herein, CGA supplementation (150 mg/kg body weight) for 14 weeks significantly prevented obesity and insulin resistance, cognitive–behavioral disturbances, and synaptic dysfunction induced by a high-fat and high-fructose diet (HFFD). Moreover, CGA supplementation enhanced the expression of genes enriched in the neuroactive ligand–receptor interaction pathway and reduced inflammatory factor expressions. Furthermore, CGA treatment increased gut microbiota diversity and the level of bacterial genera producing SCFAs. CGA also decreased the concentration of energy metabolism substrates, while it increased phosphorylcholine. Finally, we observed a significant correlation among synaptic transmission genes, gut microbiota, and neurotransmission in the CGA supplementation group by targeted multiomics analysis. Together, our results supported that the alteration of gut microbiota and metabolite composition is the underlying mechanism of CGA improving cognitive function. CGA is also a promising intervention strategy to prevent HFFD-induced cognitive impairment.

Asiatic acid alleviates metabolism disorders in ob/ob mice: mechanistic insights

“…A homeostasis model was then used to evaluate insulin resistance (HOMA-IR) using the formula HOMA-IR = (FBG × FINS)/22.5, and insulin sensitivity was determined using the formula insulin sensitivity = ln[1/(FBG × FINS)], where FBG is the fasting blood glucose level and FINS is the fasting serum insulin level. 13…”

“…A homeostasis model was then used to evaluate insulin resistance (HOMA-IR) using the formula HOMA-IR = (FBG × FINS)/22.5, and insulin sensitivity was determined using the formula insulin sensitivity = ln[1/(FBG × FINS)], where FBG is the fasting blood glucose level and FINS is the fasting serum insulin level. 13 2.5.3 Histopathological analysis. Fresh liver tissue samples were fixed in 4% paraformaldehyde for more than 24 h, dehydrated with absolute ethanol based on a standard ethanol gradient, embedded in paraffin, and sectioned into 4 μm tissue sections.…”

Preclinical Studies of Natural Products Targeting the Gut Microbiota: Beneficial Effects on Diabetes

“…Meanwhile, it regulated the abundance of norank_f_Ruminococcaceae , Monoglobus , and Candidatus_Saccharimonas at the genus level. Interestingly, chlorogenic acid might enhance energy metabolism and synaptic transmission in the brain of high-fat and high-fructose diet (HFFD)-induced mice by modulating the gut microbiota and metabolites, suggesting that the gut-brain axis played an important role in diabetes-related cognitive impairment …”

“…Interestingly, chlorogenic acid might enhance energy metabolism and synaptic transmission in the brain of high-fat and highfructose diet (HFFD)-induced mice by modulating the gut microbiota and metabolites, suggesting that the gut-brain axis played an important role in diabetes-related cognitive impairment. 111 To note, only a small fraction of the natural polyphenols are absorbed in the small intestine, while the rest are not absorbed until metabolized by microbes in the colon. 112 Therefore, the microbial metabolites of polyphenols may be the material basis for their pharmacological effects.…”

Hypertension of liver-yang hyperactivity syndrome induced by a high salt diet by altering components of the gut microbiota associated with the glutamate/GABA-glutamine cycle

“…The gut microbiota has been recognized as an important and independent metabolic organ. The gut microbiota and its metabolites are considered key regulators of brain–gut function ( 11 ) and have attracted widespread attention owing to associations with chronic diseases ( 12 ). Diet affects the composition of the gut microbiota and dysbiosis of gut microbiota has been found in both patients with hypertension and preclinical models ( 13 – 16 ).…”