Design, synthesis and biological evaluation of hesperetin derivatives as potent anti-inflammatory agent

Fitoterapia. 2017 Sep:121:212-222. doi: 10.1016/j.fitote.2017.07.016. Epub 2017 Aug 1.

Abstract

A flavonoid hesperetin is reported to have a variety of biological activities, including anticancer, antiviral, antioxidant, neuroprotective and anti-inflammatory properties. Thirty-one novel hesperetin derivatives were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells and CCl4-induced acute liver injury model. Among these compounds, 5b displayed the excellent anti-inflammatory activity on decreasing NO, IL-6 and TNF-α both in vitro and vivo. In addition, 5b could also reduce the release of NO, IL-6 and TNF-α production by LPS stimulated RAW 264.7 cell through MAPK and NF-κB signaling pathway in a concentration dependent manner. From in vivo study, it was also observed that 5b attenuated liver histopathologic changes in mouse models.

Keywords: Acute liver injury; Anti-inflammatory; Hesperetin; MAPK and NF-κB; Synthesis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / pharmacology*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Hesperidin / chemical synthesis
  • Hesperidin / pharmacology*
  • Interleukin-6 / metabolism
  • Liver / drug effects
  • MAP Kinase Signaling System / drug effects
  • Macrophages / drug effects
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • RAW 264.7 Cells
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Interleukin-6
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • Nitric Oxide
  • Hesperidin
  • hesperetin