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

Abstract

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.

The Ameliorative Effect of Apigenin or Silymarin as Add-On Therapy to Risperidone on Valproic Acid Induced Autism in Albino Rats: Implication of Oxidative Stress, Apoptosis and Autophagy

“…Groups treated with risperidone or apigenin or silymarin showed significant increases in alternation score. This impact is agreed with preceding research (22)(23)(24) that observed that risperidone, apigenin and silymarin enhanced the behavior in T-maze.…”

Mechanism of Yixishu lotion in the treatment of vaginitis based on network pharmacology combined with experimental validation: an experimental research study

“…Mitogen-activated protein kinase (MAPK) is a kind of intracellular serine/threonine protein kinase that plays a key role in cell proliferation, inflammation, immunity, oxidative stress, etc. 19 , 20 . As a key molecule of the p38MAPK signaling pathway, MAPK14 is closely related to the decline of immunity, inflammation, and oxidative stress caused by body dysfunction 20 , 21 .…”

“… 19 , 20 . As a key molecule of the p38MAPK signaling pathway, MAPK14 is closely related to the decline of immunity, inflammation, and oxidative stress caused by body dysfunction 20 , 21 . Fibroblast growth factor 2 (FGF2) plays an important role in regulating the inflammatory response in inflammatory diseases 22 .…”

Pharmaceutical prospects of Silymarin for the treatment of neurological patients: an updated insight

“…These disorders are linked with the increased probability of developing other major NDs ( Jacob et al, 2010 ; Byers and Yaffe, 2011 ). Silymarin has been found to have a vital role in the treatment of such psychiatric disorders through different mechanisms ( Grant and Odlaug, 2015 ; Khoshnoodi et al, 2015 ; Thakare et al, 2017 , 2018 ; El-Elimat et al, 2018; Kosari-Nasab et al, 2018 ; Yön et al, 2019 ; Tabaa et al, 2022 ). In the forced swim and tail suspension tests, silymarin administration significantly decreased the immobility period in mice, indicating that it may have antidepressant effects ( Bansal et al, 2013 ; Khoshnoodi et al, 2015 ; Thakare et al, 2016 ).…”

“…Silibinin upregulates the expression of BDNF/TrkB and inhibits hippocampal neurons’ autophagy, hence ameliorating cognitive decline during neurological disorders ( Song et al, 2017 ). Tabaa et al (2022) have also shown the modulation of endogenous dynorphin (Dyn)/glial cell line-derived neurotrophic factor (GDNF) and mitogen-activated protein kinase (MAPK) pathway by Silymarin during neurological disorders. This study found that Silymarin increases interleukin 10 (IL-10), GDNF and Dyn levels, decreases IFN-γ, TNFα, and IL-1β levels, and down-regulated the MAPK pathway.…”