Salem Hoda A, Elsherbiny Nehal, Alzahrani Sharifa, Alshareef Hanan M, Abd Elmageed Zakaria Y, Ajwah Sadeem M, Hamdan Ahmed M E, Abdou Yahia S, Galal Omneya O, El Azazy Marwa K A, Abu-Elfotuh Karema
Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia.
Department of Clinical Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
Pharmaceuticals (Basel). 2022 Aug 17;15(8):1012. doi: 10.3390/ph15081012.
Monosodium glutamate (MSG) is one of the most widely used food additives. However, it has been linked to protein malnutrition (PM) and various forms of toxicities such as metabolic disorders and neurotoxic effects. The current study is the first to explore the association between MSG, PM, and induced brain injury similar to attention-deficit/hyperactivity disorder (ADHD). Moreover, we determined the underlying mechanistic protective pathways of morin hydrate (MH)-a natural flavonoid with reported multiple therapeutic properties. PM was induced by feeding animals with a low protein diet and confirmed by low serum albumin measurement. Subsequently, rat pups were randomized into seven groups of 10 rats each. Group I, III, and VI were normally fed (NF) and groups II, IV, V, and VII were PM fed. Group I served as normal control NF while Group II served as PM control animals. Group III received NF + 0.4 g/kg MSG, Group IV: PM + 0.4 g/kg MSG, Group V: PM + 60 mg/kg MH, Group VI: NF + 0.4 kg/g MSG + 60 mg/kg MH and Group VII: PM + 0.4 kg/kg MSG + 60 mg/kg MH. At the end of the experimental period, animals were subjected to behavioral and biochemical tests. Our results showed that treatment of rats with a combination of MSG + PM-fed exhibited inferior outcomes as evidenced by deteriorated effects on behavioral, neurochemical, and histopathological analyses when compared to rats who had received MSG or PM alone. Interestingly, MH improved animals' behavior, increased brain monoamines, brain-derived neuroprotective factor (BDNF), antioxidant status and protein expression of Nrf2/HO-1. This also was accompanied by a significant decrease in brain MDA, inflammatory markers (NF-kB, TNF-α and IL1β), and suppression of TLR4/NLRP3/caspase-1 axis. Taken together, MSG and/or PM are associated with neuronal dysfunction. Our findings suggest MH as a potential neuroprotective agent against brain insults via targeting Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome signaling pathways.
味精（MSG）是使用最广泛的食品添加剂之一。然而，它与蛋白质营养不良（PM）以及各种形式的毒性有关，如代谢紊乱和神经毒性作用。当前的研究首次探讨了味精、蛋白质营养不良与诱发的类似于注意力缺陷多动障碍（ADHD）的脑损伤之间的关联。此外，我们确定了具有多种治疗特性的天然黄酮类化合物水合桑色素（MH）的潜在机制保护途径。通过给动物喂食低蛋白饮食诱导蛋白质营养不良，并通过测定低血清白蛋白进行确认。随后，将幼鼠随机分为七组，每组10只大鼠。第一组、第三组和第六组正常喂养（NF），第二组、第四组、第五组和第七组为蛋白质营养不良喂养。第一组作为正常对照NF，而第二组作为蛋白质营养不良对照动物。第三组接受NF + 0.4 g/kg味精，第四组：蛋白质营养不良 + 0.4 g/kg味精，第五组：蛋白质营养不良 + 60 mg/kg MH，第六组：NF + 0.4 kg/g味精 + 60 mg/kg MH，第七组：蛋白质营养不良 + 0.4 kg/kg味精 + 60 mg/kg MH。在实验期结束时，对动物进行行为和生化测试。我们的结果表明，与单独接受味精或蛋白质营养不良的大鼠相比，用味精 + 蛋白质营养不良联合处理的大鼠在行为、神经化学和组织病理学分析方面表现出较差的结果，这证明了其恶化的影响。有趣的是，MH改善了动物的行为，增加了脑单胺、脑源性神经保护因子（BDNF）、抗氧化状态以及Nrf2/HO-1的蛋白表达。这还伴随着脑丙二醛、炎症标志物（NF-κB、TNF-α和IL1β）的显著降低，以及TLR4/NLRP3/caspase-1轴的抑制。综上所述，味精和/或蛋白质营养不良与神经元功能障碍有关。我们的研究结果表明，MH作为一种潜在的神经保护剂，可通过靶向Nrf2/HO-1并阻碍TLR4/NLRP3炎性小体信号通路来对抗脑损伤。
