Palmatine alleviates LPS-induced acute lung injury via interfering the interaction of TAK1 and TAB1

Biochem Pharmacol. 2022 Aug:202:115120. doi: 10.1016/j.bcp.2022.115120. Epub 2022 Jun 24.

Abstract

Acute lung injury (ALI) is a severe clinical disease marked by uncontrolled inflammation response which lacks effective medicines. Accumulative evidence has indicated that macrophages are therapeutic targets for treating ALI because of its critical role in the inflammatory response.Palmatine (PAL), an isoquinoline alkaloid extracted from natural plants, exhibits effective anti-inflammatory, anti-tumor, and anti-oxidation activities. Here we reported that PAL alleviated LPS-induced acute lung injury and attenuated inflammatory cell infiltration especially neutrophils. Moreover, PAL also attenuated the production of TNF-α, CXCL-1, CXCL-2 and nitric oxide in bronchoalveolar lavage fluid. In addition, PAL remarkably reduced LPS-induced expression of TNF-α, CXCL-1 and CXCL-2 in bone marrow derived macrophages (BMDMs) and alveolar macrophages (AMs). Treatment with PAL inhibited the phosphorylation and interaction of TAK1/TAB1, which in turn attenuated the p38 MAPK and NF-κB signal pathways in BMDMs. Our results indicated that PAL ameliorated LPS-induced ALI by inhibiting macrophage activation through inhibiting NF-κB and p38 MAPK pathways, suggesting that PAL has anti-inflammation effect on ALI.

Keywords: Acute lung injury; Lipopolysaccharide; Macrophage; Palmatine (PAL); TAK1 and TAB1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury* / chemically induced
  • Acute Lung Injury* / drug therapy
  • Acute Lung Injury* / metabolism
  • Adaptor Proteins, Signal Transducing / metabolism
  • Berberine Alkaloids
  • Cytokines / metabolism
  • Humans
  • Lipopolysaccharides*
  • Lung
  • MAP Kinase Kinase Kinases / metabolism
  • NF-kappa B / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Berberine Alkaloids
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • TAB1 protein, human
  • Tumor Necrosis Factor-alpha
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • palmatine