Phyllanthus emblica L. polysaccharides attenuate anxiety disorder-like behavior in high-fat diet-fed mice

Abstract

Obesity, primarily driven by the widespread adoption of Western dietary patterns and sedentary lifestyles, has been associated with a spectrum of metabolic and neuropsychiatric disorders. Accumulating evidence suggests that a high-fat diet (HFD) contributes not only to metabolic dysfunction but also to neuroinflammatory processes and mood disturbances such as anxiety and depression. The mechanisms through which polysaccharides extracted from Phyllanthus emblica L. (PEP), an α-acidic pyran heteropolysaccharide (1.226 × 10 3 kDa) rich in galactose and galacturonic acid, exert beneficial effects on behavior have not been fully elucidated. In this study, we investigated the potential of PEP to attenuate HFD-induced anxiety-and depressionlike behaviors in mice. Behavioral analyses revealed significant improvements in both exploratory and stress-related behaviors following PEP administration. At the molecular level, PEP markedly reduced the expression of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and MCP-1, while concurrently enhancing the expression of anti-inflammatory mediators, including IL-4 and IL-10. Furthermore, PEP modulated the TLR4/MyD88/NF-κB signaling cascade and exerted bidirectional regulation on the AMPK/mTOR axis, upregulating AMPK while inhibiting mTOR expression, suggesting promotion of autophagic activity. These findings indicate that PEP confers neuroprotective effects by dampening neuroinflammation and improving behavioral outcomes. Collectively, our results support the potential application of PEP as a natural preventive agent for the management of diet-induced mood disorders.