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. 2020 Jun;38(1):163-174.
doi: 10.1007/s12640-020-00197-x. Epub 2020 Mar 28.

Hispidulin Inhibits Neuroinflammation in Lipopolysaccharide-Activated BV2 Microglia and Attenuates the Activation of Akt, NF-κB, and STAT3 Pathway

Chung-I Yu  1 , Cheng-I Cheng  2 , Ya-Fei Kang  3 , Po-Chih Chang  4   5   6 , In-Pin Lin  7 , Yu-His Kuo  7 , An-Jie Jhou  7 , Mei-Ying Lin  8 , Chung-Yi Chen  9 , Chien-Hsing Lee  10   11   12
Affiliations

Hispidulin Inhibits Neuroinflammation in Lipopolysaccharide-Activated BV2 Microglia and Attenuates the Activation of Akt, NF-κB, and STAT3 Pathway

Chung-I Yu et al. Neurotox Res. 2020 Jun.

Abstract

Microglia, resident innate immune cells in central nervous system, regulates neuroinflammation and is associated with a variety of neuropathologies. The present study investigated the antineuroinflammatory effects of hispidulin (HPD), a naturally flavone compound, in lipopolysaccharide- (LPS-) stimulated BV2 microglia cells. The expression levels of nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory factors were determined by the Griess method, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). Western blotting was used to measure various transcription factors such as Akt, nuclear factor-kappa B (NF-κB), and signal transducer and activator of transcription 3 (STAT3) activities. Our experimental results demonstrated that HPD increased cell viability and reduced apoptosis in LPS-treated BV2 microglia cells. Moreover, HPD significantly reduced the levels of NO, ROS, inducible nitric oxide synthase (iNOS), cyclooxygenase- (COX-) 2, tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, and prostaglandin E2 (PGE2) in a dose-dependent manner. Phosphorylation of NF-κB/IκB, Akt, and STAT3 proteins expression by HPD was suppressed in LPS-induced BV2 microglial cells. We concluded that HPD may inhibit neuroinflammatory responses by inhibiting NF-κB pathway activation and ROS formation. These results propose that HPD has potential as anti-inflammatory agents against microglia-mediated neuroinflammatory disorders.

Keywords: Akt; Flavone compound; Hispidulin; Microglia-mediated neuroinflammatory disorders; NF-κB/IκB; STAT3.

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