Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways
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Online ISSN 1976-3786 Print ISSN 0253-6269
RESEARCH ARTICLE
Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways Sun Hyo Jo1 • Mi Eun Kim1 • Jun Hwi Cho1 • Yujeong Lee2 • Jaewon Lee2 Yong-Duk Park3 • Jun Sik Lee1
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Received: 24 January 2019 / Accepted: 16 July 2019 The Pharmaceutical Society of Korea 2019
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 antineuroinflammatory 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 LPSstimulated BV-2 microglial cells. Hesperetin also significantly reduced secretion of inflammatory cytokines including interleukin (IL)-1b 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.
Sun Hyo Jo, Mi Eun Kim, and Jun Hwi Cho have contributed equally. & Jun Sik Lee [email protected] 1
Department of Life Science, Immunology Research Lab, BK21-plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, Dong-gu, Gwangju 61452, Republic of Korea
2
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 46241, Republic of Korea
3
Department of Preventive and Society Dentistry, School of Dentistry, Djkunghee Hospital, Kyung Hee University, Seoul 02447, Republic of Korea
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. Keywords Hesperetin Neuroinflammation Inflammatory cytokines IL-1 IL-6 MAPK Microglia
Introduction The increasing prevalence of neurological and brain-related diseases is an important issue in an aging society (Mecocci et al. 2018). These conditions are associated with neuroinflammation. Neurodegenerative disease is defined by progressive dysfunction of the nervous system and includes Parkinson’s disease (PD) and Alzheimer’s disease (AD) (Reale et al. 2010; Pennisi et al. 2017; Tiwari and Pal 2017). The neuroinflammatory response defends against exogenous antigens, but chronic neuroinflammation is involved in various neurodegenerative disorders. In the central nervous s
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