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

• Published in: Archives of pharmacal research Vol. 42; no. 8; pp. 695 - 703
• Main Authors: Jo, Sun Hyo, Kim, Mi Eun, Cho, Jun Hwi, Lee, Yujeong, Lee, Jaewon, Park, Yong-Duk, Lee, Jun Sik
• Format: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.08.2019; 대한약학회
• Subjects: Animals; anti-inflammatory activity; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; antioxidant activity; astrocytes; brain; Cell Line; citrus fruits; Cytokines - antagonists & inhibitors; Cytokines - metabolism; Dose-Response Relationship, Drug; hesperetin; hesperidin; Hesperidin - chemistry; Hesperidin - pharmacology; inducible nitric oxide synthase; Inflammation - drug therapy; Inflammation - metabolism; Inflammation - pathology; interleukin-6; lipopolysaccharides; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Medicine; Mice; Microglia - drug effects; Microglia - metabolism; Microglia - pathology; mitogen-activated protein kinase; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Molecular Structure; neurodegenerative diseases; nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Pharmacology/Toxicology; Pharmacy; phosphorylation; Research Article; secretion; Structure-Activity Relationship; 약학; Hesperetin; Inflammatory cytokines; IL-1; Neuroinflammation; MAPK; IL-6; Microglia
• ISSN: 0253-6269; 1976-3786; 1976-3786
• DOI: 10.1007/s12272-019-01174-5

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.