Preventive Effect of Indian Gooseberry (Phyllanthus emblica L.) Fruit Extract on Cognitive Decline in High-Fat Diet (HFD)-Fed Rats.

SCOPE: Methylglyoxal (MG)-derived advanced glycation end products (AGEs) directly bind to the receptor for advanced glycation end products (RAGE), subsequently exacerbating obesity and obesity-induced cognitive decline. Indian gooseberry (Phyllanthus emblica L.) fruit has antiobesity properties. However, the underlying mechanism by which Indian gooseberry fruit prevents obesity-induced cognitive decline remains unclear. METHODS AND RESULTS: This study aims to investigate the preventive effect of a water extract of Indian gooseberry fruit (WEIG) and its bioactive compound gallic acid (GA) on the obesity-induced cognitive decline through MG suppression and gut microbiota modulation in high-fat diet (HFD)-fed rats. Trapping MG, WEIG, and GA significantly ameliorate fat accumulation in adipose tissue and learning and memory deficits. Mechanistically, WEIG and GA administration effectively reduces brain MG and AGE levels and subsequently reduces insulin resistance, inflammatory cytokines, MDA production, and Alzheimer's disease-related proteins, but increases both antioxidant enzyme activities and anti-inflammatory cytokine with inhibiting RAGE, MAPK, and NF-κB levels in HFD-fed rats. Additionally, WEIG and GA supplementation increases the relative abundances of Bacteroidetes, Gammaproteobacteria, and Parasutterella, which negatively correlate with MG, inflammatory cytokine, and Alzheimer's disease-related protein expressions. CONCLUSION: This novel finding provides a possible mechanism by which WEIG prevents obesity-induced cognitive decline through the gut-brain axis.