Pharmacology & Environmental Toxicology, Environmental Studies & Research Institute (ESRI), University of Sadat City, Minofia Governorate, Sadat city, Egypt.
Biochemistry, Environmental Studies & Research Institute (ESRI), University of Sadat City, Sadat City, Egypt.
Inflammopharmacology. 2022 Jun;30(3):961-980. doi: 10.1007/s10787-022-00961-9. Epub 2022 Apr 2.
Neuroinflammation, a major component of many CNS disorders, has been suggested to be associated with diacetyl (DA) exposure. DA is commonly used as a food flavoring additive and condiment. Lately, silymarin (Sily) has shown protective and therapeutic effects on neuronal inflammation. The study aimed to explore the role of Sily in protecting and/or treating DA-induced neuroinflammation. Neuroinflammation was induced in rats by administering DA (25 mg/kg) orally. Results revealed that Sily (50 mg/kg) obviously maintained cognitive and behavioral functions, alleviated brain antioxidant status, and inhibited microglial activation. Sily enhanced IL-10, GDNF and Dyn levels, reduced IFN-γ, TNFα, and IL-1β levels, and down-regulated the MAPK pathway. Immunohistochemical investigation of EGFR and GFAP declared that Sily could conserve neurons from inflammatory damage. However, with continuing DA exposure during Sily treatment, oxidative stress and neuroinflammation were less mitigated. These findings point to a novel mechanism involving the Dyn/GDNF and MAPK pathway through which Sily might prevent and treat DA-induced neuroinflammation.
神经炎症是许多中枢神经系统疾病的主要组成部分，据认为与二乙酰（DA）暴露有关。DA 通常用作食品调味添加剂和调味料。最近，水飞蓟素（Sily）已显示出对神经元炎症的保护和治疗作用。本研究旨在探讨 Sily 在保护和/或治疗 DA 诱导的神经炎症中的作用。通过口服给予 DA（25mg/kg）在大鼠中诱导神经炎症。结果表明，Sily（50mg/kg）明显维持认知和行为功能，减轻大脑抗氧化状态，并抑制小胶质细胞激活。Sily 增加了 IL-10、GDNF 和 Dyn 的水平，降低了 IFN-γ、TNFα 和 IL-1β 的水平，并下调了 MAPK 途径。EGFR 和 GFAP 的免疫组织化学研究表明，Sily 可以保护神经元免受炎症损伤。然而，在 Sily 治疗期间持续暴露于 DA 时，氧化应激和神经炎症的缓解程度较低。这些发现表明了一种涉及 Dyn/GDNF 和 MAPK 途径的新机制，通过该机制，Sily 可能预防和治疗 DA 诱导的神经炎症。
