Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways
Jo Sun-Hyo, 김미은, 조준휘, 이유정, 이재원, 박용덕, 이준식,
소속 상세정보
( Jo Sun-Hyo )
Chosun University College of Natural Sciences Department of Life Science
김미은 ( Kim Mi-Eun )
Chosun University College of Natural Sciences Department of Life Science
조준휘 ( Cho Jun-Hwi )
Chosun University College of Natural Sciences Department of Life Science
이유정 ( Lee Yu-Jeong )
Pusan National University College of Pharmacy Department of Pharmacy
이재원 ( Lee Jae-Won )
Pusan National University College of Pharmacy Department of Pharmacy
박용덕 ( Park Yong-Duk )
Kyung Hee University School of Dentistry Department of Preventive and Social Dentistry
이준식 ( Lee Jun-Sik )
Chosun University College of Natural Sciences Department of Life Science
Abstract
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.
키워드
Hesperetin; Neuroinflammation; Inflammatory cytokines; IL-1; IL-6; MAPK; Microglia
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