Reduning injection ameliorates paraquat-induced acute lung injury by regulating AMPK/MAPK/NF-κB signaling

J Cell Biochem. 2019 Aug;120(8):12713-12723. doi: 10.1002/jcb.28540. Epub 2019 Mar 12.

Abstract

Reduning injection (RDN), a patented Chinese medicine, is broadly used for common cold and lung infection in clinic, but the mechanism underlying its effects on inflammation-related pulmonary injury remains unclear. Paraquat (PQ, bolus 15 mg/kg dose, ip) was administered for acute lung injury induction in mice, which were orally administered dexamethasone (2 mg/kg) or RDN (50 and 100 mg/kg/day) for 5 days. After treatment, plasma and lung tissue samples from the euthanized animals were obtained and analyzed by histological, biochemical and immunoblot assays. Histological observation demonstrated RDN alleviated PQ-induced lung damage. Meanwhile, RDN suppressed myeloperoxidase (MPO) activity, reduced the wet/dry (W/D) ratio and decreased the amounts of total leukocytes and neutrophils. Treatment also markedly decreased the amounts of malondialdehyde, MPO, and inflammatory cytokines while increasing superoxide dismutase activity in comparison with the PQ group. In immunoblot, RDN blocked the phosphorylation levels of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), JNK, ERK, p38, inhibitor of nuclear factor κB kinase and nuclear factor-κB (NF-κB) in lung tissue specimens in PQ-challenged animals, which was further verified in vitro. The above data indicated protective effects for RDN in PQ-induced lung damage, possibly through inhibition of the AMPK/MAPK/NF-κB pathway.

Keywords: AMPK; MAPK; NF-κB; Reduning injection; paraquat; pulmonary injury.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • AMP-Activated Protein Kinases / metabolism
  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Administration, Oral
  • Animals
  • Dexamethasone / administration & dosage*
  • Dexamethasone / pharmacology
  • Disease Models, Animal
  • Drugs, Chinese Herbal / administration & dosage*
  • Drugs, Chinese Herbal / pharmacology
  • Gene Expression Regulation / drug effects
  • Humans
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Paraquat / administration & dosage
  • Paraquat / adverse effects*
  • Peroxidase / metabolism
  • Phosphorylation
  • Signal Transduction / drug effects*

Substances

  • Drugs, Chinese Herbal
  • NF-kappa B
  • reduning
  • Dexamethasone
  • Peroxidase
  • Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • Paraquat