Biofunctional Pectin Derived from Pomelo Peel: Structural Insights and Neuro–Gut Protective Mechanisms in Zebrafish under Bisphenol AF-Induced Neurotoxicity

Abstract

Pomelo ( Citrus maxima cv. Wentan) peel represents a major agricultural byproduct rich in pectin with potential applications in functional foods and biomedical materials. This study aimed to elucidate the structure–activity relationship of pomelo peel pectin extracted at different temperatures (100 to 140 °C) and to evaluate its neuro–gut protective effects using a zebrafish model. Pectins obtained under varying thermal conditions were structurally characterized, and their bioactivities were systematically compared. Among them, pectin extracted at 130 °C (P-130) exhibited higher galacturonic acid content, molecular weight, and hydroxyl group abundance. Functionally, P-130 effectively mitigated bisphenol AF-induced toxicity in zebrafish. It significantly improved developmental outcomes, reduced oxidative stress, and preserved neuronal integrity by promoting axonal growth and up-regulating neurodevelopment-related genes. Notably, P-130 regulated the gut–brain axis by restoring neurotransmitter balance (5-hydroxytryptamine and dopamine), attenuating intestinal inflammation, and modulating gut microbiota composition, particularly by enriching beneficial taxa such as Bacteroidetes. These effects were associated with reduced anxiety-like behavior. Histopathological analyses further confirmed its protective roles in cerebellar and intestinal tissues. This study highlights the critical influence of extraction temperature on pectin structure and identifies P-130 as a promising natural agent against environmental toxicants. The findings provide novel insights into the synergistic mechanisms linking antioxidant activity, neuroprotection, and microbiota regulation, offering a scientific basis for the valorization of pomelo peel in developing plant-derived protective strategies.