Licochalcone A Inhibits Prostaglandin E2 by Targeting the MAPK Pathway in LPS Activated Primary Microglia
2023
Harsharan Singh Bhatia | Matthias Apweiler | Lu Sun | Julian Baron | Ashwini Tirkey | Bernd L. Fiebich
Neuroinflammation and oxidative stress are conditions leading to neurological and neuropsychiatric disorders. Natural compounds exerting anti-inflammatory and anti-oxidative effects, such as Licochalcone A, a bioactive flavonoid present in a traditional Chinese herb (licorice), might be beneficial for the treatment of those disorders. Therefore, this study aimed to investigate the anti-inflammatory and anti-oxidative effects of Licochalcone A in LPS-activated primary rat microglia. Licochalcone A dose-dependently prevented LPS-induced PGE2 release by inhibiting the arachidonic acid (AA)/cylcooxygenase (COX) pathway decreasing phospholipase A2, COX-1, and COX-2 protein levels. Furthermore, LPS-induced levels of the cytokines IL-6 and TNF&alpha: were reduced by Licochalcone A, which also inhibited the phosphorylation and, thus, activation of the mitogen-activated protein kinases (MAPK) p38 MAPK and Erk 1/2. With the reduction of 8-iso-PGF2&alpha:, a sensitive marker for oxidative stress, anti-oxidative effects of Licochalcone A were demonstrated. Our data demonstrate that Licochalcone A can affect microglial activation by interfering in important inflammatory pathways. These in vitro findings further demonstrate the potential value of Licochalcone A as a therapeutic option for the prevention of microglial dysfunction related to neuroinflammatory diseases. Future research should continue to investigate the effects of Licochalcone A in different disease models with a focus on its anti-oxidative and anti-neuroinflammatory properties.
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