Silla Alessia, Punzo Angela, Caliceti Cristiana, Barbalace Maria Cristina, Hrelia Silvana, Malaguti Marco
Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna, 40126 Bologna, Italy.
Department for Life Quality Studies, Alma Mater Studiorum, University of Bologna, 47921 Rimini, Italy.
Antioxidants (Basel). 2025 May 11;14(5):581. doi: 10.3390/antiox14050581.
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.
在正常情况下，神经炎症会诱导小胶质细胞和星形胶质细胞活化以维持脑内稳态。然而，过度或长期的神经炎症会对脑组织造成有害损伤。许多因素可引发慢性神经炎症，最终导致神经退行性变。在此背景下，鉴于迫切需要新的天然方法来减轻神经炎症损伤，人们将目光转向了诸如农业副产品等非传统来源。柑橘类水果在全球广泛食用，会产生大量废弃物，包括果皮、种子和果肉。这些副产品传统上被视为农业废弃物，如今却被认为是生物活性化合物的宝贵来源，包括黄酮类化合物、类胡萝卜素、萜类化合物和柠檬苦素类化合物。其中，柑橘多酚——尤其是橙皮苷、柚皮素和圣草次苷等黄烷酮类化合物——已成为神经炎症通路的有效调节剂，它们通过与细胞抗氧化系统、促炎信号级联反应、神经血管完整性和肠-脑轴动态变化的多方面相互作用发挥作用。本综述旨在描述柑橘废弃物中存在的关键分子，并综合临床前和临床证据，以阐明神经退行性疾病中神经炎症的生化机制。
