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.
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Abbreviations
- LPS:
-
lipopolysaccharide
- HPD:
-
hispidulin
- ROS:
-
reactive oxygen species
- COX-2:
-
cyclooxygenase-2
- ELISA:
-
enzyme-linked immunosorbent assay
- FBS:
-
fetal bovine serum
- IL-1β:
-
interleukin-1β
- IL6:
-
interleukin-6
- TNF-α:
-
tumor necrosis factor
- iNOS:
-
inducible NO synthase
- NF-κB:
-
nuclear factor-κB
- NO:
-
nitric oxide
- PGE2:
-
prostaglandin E2
- STAT3:
-
signal transducer and activator of transcription 3
- MTT:
-
3-(4, 5-dimethylthiazol- 2-yl)- 2, 5-diphenyl tetrazolium bromide
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Funding
This study was funded by grants from the Tainan Sin-Lau Medical Foundation, the Presbyterian Church in Taiwan (SLH-107-09), the Ministry of Science and Technology of Taiwan (MOST 108-2320-B-037-018), the Chi-Mei Medical Center Liouying Research Grant (CLFHR10735; CLFHR10733), and the Kaohsiung Medical University Research Foundation (KMU-Q108014; KMU-Q108023).
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Yu, CI., Cheng, CI., Kang, YF. et al. Hispidulin Inhibits Neuroinflammation in Lipopolysaccharide-Activated BV2 Microglia and Attenuates the Activation of Akt, NF-κB, and STAT3 Pathway. Neurotox Res 38, 163–174 (2020). https://doi.org/10.1007/s12640-020-00197-x
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DOI: https://doi.org/10.1007/s12640-020-00197-x