Chrysin promotes resolution of LPS-induced neuroinflammation by modulating glial reactivity and inflammatory response

Neuroinflammation, mainly driven by activated microglia and astrocytes, plays a key role in the pathogenesis of several neurodegenerative disorders [1]. Chrysin, a natural flavonoid found in fruits, vegetables and mushrooms [2] has been reported to exert anti-inflammatory and neuroprotective effects [3]. In this study we investigated the impact of chrysin on lipopolysaccharide (LPS)-induced in vivo mouse model of prolonged inflammatory response, focusing on two different brain areas, namely caudate-putamen (CP) and hippocampus (HIP). The effects of chrysin at 72h on cytokine expression, particularly of the anti-inflammatory cytokine IL-10 and pro-inflammatory IL-6 cytokine, Toll like receptor 4 (TLR4) and phosphoinositide 3-kinase (PIK3) were evaluated by qPCR. In addition, confocal microscopy was performed using the microglial marker IBA1 and the astrocytic marker GFAP. As a result, LPS induced a marked neuroinflammatory response in both brain regions, characterized by increased IL-6 expression, modulation of innate immune signalling path- ways including TLR4 and PIK3, and marked activation of microglia and astrocytes as shown by the IBA1 and GFAP staining. Chrysin alone induced a significant up- regulation of IL-10, suggesting that it promotes a strong anti-inflammatory immunoregulatory environment. Notably, chrysin pretreatment in LPS-chrysin mice sig- nificantly attenuated LPS-induced neuroinflammation and reshaped late inflammatory state. Overall, these findings demonstrate that chrysin counteracts LPS- induced neuroinflammation reducing microglial and astrocytic activation and creating an immunomodulatory environment, shaping the resolutive phase of inflammation. These findings support the potential role of chrysin as an important neuroprotective compound in neuroinflammatory dysfunctions.