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KMID : 0043320190420080695
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Archives of Pharmacal Research
2019 Volume.42 No. 8 p.695 ~ p.703
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Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways
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Jo Sun-Hyo
Kim Mi-Eun
Cho Jun-Hwi
Lee Yu-Jeong
Lee Jae-Won
Park Yong-Duk
Lee Jun-Sik
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Abstract
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Neuroinflammation is a specific or nonspecific immunological reaction in the central nervous system that is induced by microglia activation. Appropriate regulation of activated microglial cells is therefore important for inhibiting neuroinflammation. Hesperetin is a natural flavanone and an aglycone of hesperidin that is found in citrus fruits. Hesperetin reportedly possesses anti-inflammatory, anti-cancer, and antioxidant effects. However, the anti-neuroinflammatory effects of hesperetin on microglia are still unknown. Here, we investigated the anti-neuroinflammatory effects of hesperetin on lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We found that hesperetin strongly inhibited nitric oxide production and expression of inducible nitric oxide synthase in LPS-stimulated BV-2 microglial cells. Hesperetin also significantly reduced secretion of inflammatory cytokines including interleukin (IL)-1β and IL-6. Furthermore, hesperetin down-regulated the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase, exerting anti-inflammatory effects. Hesperetin suppressed astrocyte and microglia activation in the LPS-challenged mouse brain. Collectively, our findings indicate that hesperetin inhibits microglia-mediated neuroinflammation and could be a prophylactic treatment for neurodegenerative diseases.
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KEYWORD
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Hesperetin, Neuroinflammation, Inflammatory cytokines, IL-1, IL-6, MAPK, Microglia
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