Alpinetin inhibits lipopolysaccharide-induced acute kidney injury in mice

Int Immunopharmacol. 2015 Oct;28(2):1003-8. doi: 10.1016/j.intimp.2015.08.002. Epub 2015 Aug 28.

Abstract

Alpinetin, a novel plant flavonoid isolated from Alpinia katsumadai Hayata, has been demonstrated to have anti-inflammatory and antioxidant effects. However, the effects of alpinetin on lipopolysaccharide (LPS)-induced acute kidney injury have not been reported. In the present study, we investigated the protective effects and the underlying mechanism of alpinetin against LPS-induced acute kidney injury in mice. The results showed that alpinetin inhibited LPS-induced kidney histopathologic changes, blood urea nitrogen (BUN) and creatinine levels. Alpinetin also inhibited LPS-induced ROS, MDA, and inflammatory cytokines TNF-α, IL-6 and IL-1β production in kidney tissues. Meanwhile, Western blot analysis showed that alpinetin suppressed LPS-induced TLR4 expression and NF-κB activation in kidney tissues. In addition, alpinetin was found to up-regulate the expression of Nrf2 and HO-1 in a dose-dependent manner. In conclusion, alpinetin protected LPS-induced kidney injury through activating Nrf2 and inhibiting TLR4 expression.

Keywords: Acute kidney injury; Alpinetin; LPS; NF-κB; Nrf2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / drug therapy*
  • Alpinia*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Antioxidants / administration & dosage*
  • Flavanones / administration & dosage*
  • Gene Expression Regulation / drug effects
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Interleukin-1beta / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / pathology
  • Lipopolysaccharides / immunology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Flavanones
  • Interleukin-1beta
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • alpinetin
  • Heme Oxygenase-1
  • Hmox1 protein, mouse