The Role of Antioxidant Compounds from Citrus Waste in Modulating Neuroinflammation: A Sustainable Solution.

In normal conditions, neuroinflammation induces microglia and astrocyte activation to maintain brain homeostasis. However, excessive or prolonged neuroinflammation can inflict harmful damage on brain tissue. Numerous factors can trigger chronic neuroinflammation, ultimately leading to neurodegeneration. In this context, considering the pressing need for novel, natural approaches to mitigate neuroinflammatory damage, attention has turned to unconventional sources such as agricultural by-products. Citrus fruits are widely consumed globally, producing substantial waste, including peels, seeds, and pulp. Traditionally regarded as agricultural waste, these by-products are now recognized as valuable reservoirs of bioactive compounds, including flavonoids, carotenoids, terpenoids, and limonoids. Among these, citrus polyphenols-particularly flavanones like hesperidin, naringenin, and eriocitrin-have emerged as potent modulators of neuroinflammatory pathways through their multifaceted interactions with cellular antioxidant systems, pro-inflammatory signaling cascades, neurovascular integrity, and gut-brain axis dynamics. This review aims to characterize the key molecules present in citrus waste and synthesizes preclinical and clinical evidence to elucidate the biochemical mechanisms underlying neuroinflammation in neurodegenerative disorders.