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Archives of Pharmacal Research

, Volume 42, Issue 8, pp 695–703 | Cite as

Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways

  • Sun Hyo Jo
  • Mi Eun Kim
  • Jun Hwi Cho
  • Yujeong Lee
  • Jaewon Lee
  • Yong-Duk Park
  • Jun Sik LeeEmail author
Research Article

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.

Keywords

Hesperetin Neuroinflammation Inflammatory cytokines IL-1 IL-6 MAPK Microglia 

Notes

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

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Copyright information

© The Pharmaceutical Society of Korea 2019

Authors and Affiliations

  1. 1.Department of Life Science, Immunology Research Lab, BK21-plus Research Team for Bioactive Control Technology, College of Natural SciencesChosun UniversityGwangjuRepublic of Korea
  2. 2.Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging InterventionPusan National UniversityBusanRepublic of Korea
  3. 3.Department of Preventive and Society Dentistry, School of Dentistry, Djkunghee HospitalKyung Hee UniversitySeoulRepublic of Korea

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