Hesperetin inhibits neuroinflammation on microglia by suppressing inflammatory cytokines and MAPK pathways.
Sun Hyo JoMi Eun KimJun Hwi ChoYujeong LeeJaewon LeeYong-Duk ParkJun Sik LeePublished in: Archives of pharmacal research (2019)
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.
Keyphrases
- inflammatory response
- lps induced
- lipopolysaccharide induced
- nitric oxide
- induced apoptosis
- anti inflammatory
- neuropathic pain
- toll like receptor
- nitric oxide synthase
- signaling pathway
- cell cycle arrest
- oxidative stress
- traumatic brain injury
- transcription factor
- spinal cord
- cognitive impairment
- pi k akt
- endoplasmic reticulum stress
- poor prognosis
- cell proliferation
- cerebral ischemia
- cell death
- spinal cord injury
- immune response
- blood brain barrier