The study of polyphenols’ effects on health has been gaining attention lately. In addition to reacting with important enzymes, altering the cell metabolism, these substances can present either positive or negative metabolic alterations depending on their consumption levels. Naringenin, a citrus flavonoid, already presents diverse metabolic effects. The objective of this work was to evaluate the effect of maternal naringenin supplementation during pregnancy on the tricarboxylic acid cycle activity in offspring’s cerebellum. Adult female Wistar rats were divided into two groups: (1) vehicle (1 ml/kg by oral administration (p.o.)) or (2) naringenin (50 mg/kg p.o.). The offspring were euthanised at 7th day of life, and the cerebellum was dissected to analyse citrate synthase, isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH) and malate dehydrogenase (MDH) activities. Molecular docking used SwissDock web server and FORECASTER Suite, and the proposed binding pose image was created on UCSF Chimera. Data were analysed by Student’s t test. Naringenin supplementation during pregnancy significantly inhibited IDH, α-KGDH and MDH activities in offspring’s cerebellum. A similar reduction was observed in vitro, using purified α-KGDH and MDH, subjected to pre-incubation with naringenin. Docking simulations demonstrated that naringenin possibly interacts with dehydrogenases in the substrate and cofactor binding sites, inhibiting their function. Naringenin administration during pregnancy may affect cerebellar development and must be evaluated with caution by pregnant women and their physicians.

中文翻译：

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柚皮素抑制三羧酸循环脱氢酶：实验和分子模型证据

多酚对健康影响的研究近来备受关注。除了与重要的酶发生反应，改变细胞代谢外，这些物质还可以根据其消耗水平呈现正或负的代谢变化。柚皮素是一种柑橘类黄酮类化合物，已经呈现出多种代谢作用。这项工作的目的是评估母体在怀孕期间补充柚皮素对后代小脑三羧酸循环活性的影响。成年雌性 Wistar 大鼠分为两组：（1）载体（1 ml/kg 口服给药（po））或（2）柚皮素（50 mg/kg po）。后代在第 7 天被安乐死，解剖小脑以分析柠檬酸合酶、异柠檬酸脱氢酶 (IDH)、α-酮戊二酸脱氢酶（α-KGDH) 和苹果酸脱氢酶 (MDH) 活性。分子对接使用 SwissDock 网络服务器和 FORECASTER Suite，提出的绑定姿势图像是在 UCSF Chimera 上创建的。数据由学生分析吨测试。怀孕期间补充柚皮素可显着抑制 IDH，α-后代小脑中的KGDH和MDH活动。观察到类似的减少体外, 使用纯化的α-KGDH 和 MDH，与柚皮素预孵育。对接模拟表明，柚皮素可能与底物和辅因子结合位点中的脱氢酶相互作用，从而抑制它们的功能。妊娠期间服用柚皮素可能会影响小脑发育，孕妇及其医生必须谨慎评估。