6-Gingerol via overexpression of miR-322-5p impede lipopolysaccharide-caused inflammatory response in RAW264.7 cells

Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec;396(12):3797-3807. doi: 10.1007/s00210-023-02543-0. Epub 2023 Jun 22.

Abstract

Acute lung injury (ALI) and sepsis are complicated syndromes that are often left untreated in critically ill patients. 6-Gingerol is a phenolic phytochemical compound that is found in fresh ginger, has pharmacological effects against inflammation. This study explored the roles of 6-gingerol in a mouse model of acute lung injury caused by lipopolysaccharide (LPS) and RAW-264.7 cells inflammation. The LPS-induced animal model underwent histopathological examinations, and RAW-264.7 cells viability was determined by Cell counting Kit-8 (CCk-8) assay. Additionally, qRT-PCR, Immunofluorescence, Western blot, and ELISA were used in vivo and in vitro to identify inflammatory factors and proteins associated with NF-κB and MAPK signaling pathways. In a histological examination 6-gingerol exhibited protective effects. Moreover, 6-gingerol elevated cell viability and downregulated inflammatory factors Interlukin-1β (IL-1β), Interlukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α) in LPS-treated RAW-264.7 cells. Furthermore, 6-gingerol decreased phosphorylation of P65, P38 and the level of JNK in NF-κB and MAPK pathways. Importantly, 6-gingerol increased transcript abundance of miR-322-5p which suppressed by LPS and miR-322-5p downregulation negated the protective functions of 6-gingerol. The protective activity of 6-gingerol was mediated by miR-322-5p up-regulation.

Keywords: 6-Gingerol; Acute lung injury; Lipopolysaccharides; MAPK; NF-κB; miR-322-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury* / pathology
  • Animals
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Lipopolysaccharides / toxicity
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NF-kappa B / metabolism
  • RAW 264.7 Cells
  • Signal Transduction

Substances

  • NF-kappa B
  • Lipopolysaccharides
  • gingerol
  • MicroRNAs
  • MIRN322 microRNA, mouse