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The therapeutic effects of Jaceosidin on lipopolysaccharide-induced acute lung injury in mice

J Pharmacol Sci. 2019 Jul;140(3):228-235. doi: 10.1016/j.jphs.2019.07.004. Epub 2019 Jul 18.

Abstract

Acute lung injury (ALI) results from various factors including uncontrolled pulmonary inflammation, oxidative damage and the over-activated complement with high mortality rates. Jaceosidin was a flavonoid compound with significant anti-complement activity. We aimed to investigate the therapeutic effects of Jaceosidin on ALI induced by lipopolysaccharide (LPS). Mice were orally administrated with Jaceosidin (15, 30 and 60 mg/kg) after LPS challenge. 24 h after LPS challenge, Jaceosidin could significantly decrease the lung wet-to-dry weight (W/D) ratio and the protein concentration in bronchoalveolar lavage fluid (BALF). Jaceosidin could down-regulate the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), together with up-regulation the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in BALF. Jaceosidin could significantly decrease the levels of myeloperoxidase (MPO), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB), COX-2 mRNA and NF-κB p65 mRNA together with increasing the activity of catalase (CAT). Additionally, Jaceosidin attenuated lung histopathological changes, inhibited the expressions of COX-2 and NF-κB p65 and reduced complement deposition with decreasing the levels of complement 3 (C3) and complement 3c (C3c) in serum. These data suggest that Jaceocidin may dampen the inflammatory response and decrease the levels of complement together with the antioxidant activity following LPS-induced ALI.

Keywords: Acute lung injury; Complement; Inflammatory mediators; Jaceosidin; Oxyradicals.

MeSH terms

  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cyclooxygenase 2 / metabolism
  • Flavonoids / pharmacology*
  • Interleukin-10 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism
  • Peroxidase / metabolism
  • Plant Extracts / pharmacology
  • Pneumonia / drug therapy
  • Pneumonia / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Flavonoids
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • jaceosidin
  • Peroxidase
  • Cyclooxygenase 2