Icariin modulates carrageenan-induced acute inflammation through HO-1/Nrf2 and NF-kB signaling pathways

Biomed Pharmacother. 2019 Dec:120:109567. doi: 10.1016/j.biopha.2019.109567. Epub 2019 Oct 25.

Abstract

Cellular inflammation has been recognized as the leading factor in numerous diseases, causing either cell death, organ-specific damage, or genesis of different cancers. Icariin, a flavonol glucoside, extracted from Herba Epimedii, offers various pharmacological activities, including reducing inflammation and an antioxidant effect. We aimed to evaluate the anti-inflammatory mechanisms of icariin focussing on both HO-1/Nrf2 and NF-kB pathways. Acute inflammation was induced in rats via carrageenan in this study. Icariin was injected in a dose of 50 mg/kg. Icariin significantly reduced paw swelling in carrageenan-injected animals. It also ameliorated carrageenan-induced paw histopathological alterations. Icariin significantly increased paw enzymatic and non-enzymatic antioxidants. It decreased paw lipid peroxidation. Icariin decreased paw levels of inflammatory cytokines and NF-kB. The immunohistochemical analysis showed that icariin significantly increased Nrf2 gene expression while decreasing NF-kB and COX-2 gene expression. RT-PCR analysis revealed that icariin injection significantly increased both Nrf2 and HO-1 expression of mRNA. The results of this study collectively show that icariin improved carrageenan-induced paw edema by modulating HO-1/Nrf2 and NF-ĸB signaling.

Keywords: Carrageenan; HO-1; Icariin; Inflammatory cytokines; NF-kB; Nrf2.

MeSH terms

  • Acute Disease
  • Animals
  • Biomarkers / metabolism
  • Carrageenan
  • Edema / drug therapy
  • Edema / pathology
  • Flavonoids / pharmacology*
  • Flavonoids / therapeutic use
  • Heme Oxygenase-1 / metabolism*
  • Indomethacin / pharmacology
  • Indomethacin / therapeutic use
  • Inflammation / metabolism*
  • Inflammation / pathology*
  • Male
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism*
  • Oxidative Stress / drug effects
  • Rats, Wistar
  • Signal Transduction* / drug effects

Substances

  • Biomarkers
  • Flavonoids
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Carrageenan
  • Heme Oxygenase-1
  • icariin
  • Indomethacin