Silymarin constrains diacetyl-prompted oxidative stress and neuroinflammation in rats: involvements of Dyn/GDNF and MAPK signaling pathway

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-gamma, TNF alpha, and IL-1 beta 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.

Automated summary

This study reveals the protective and therapeutic effects of silymarin (Sily) on diacetyl (DA)-induced neuroinflammation. Sily is found to maintain cognitive and behavioral functions, alleviate brain antioxidant status, and inhibit microglial activation. It positively regulates cytokine levels and down-regulates the MAPK pathway, thus protecting neurons from inflammatory damage.