Hominis placenta Suppresses Acute Lung Inflammation by Activating Nrf2

Am J Chin Med. 2018;46(4):801-817. doi: 10.1142/S0192415X18500428. Epub 2018 May 13.

Abstract

Hominis placenta (HP), a dried human placenta, has been known to target liver, lung, or kidney meridians, improving the functions associated with these meridians in traditional Chinese or Asian medicine (TCM). Since recent studies implicate an HP extract in suppressing inflammation, we investigated whether an aqueous HP extract can ameliorate inflammation that occurred in the lungs. When administered with a single intratracheal lipopolysaccharide (LPS), C57BL/6 mice developed an acute neutrophilic lung inflammation along with an increased expression of pro-inflammatory cytokine genes. However, this was diminished by the administration HP extract via an intraperitoneal route 2 h after LPS treatment. Western blot and semi-quantitative RT-PCR analyses revealed that while suppressing the activity of a proinflammatory factor NF-[Formula: see text]B marginally, the HP extract strongly activated an anti-inflammatory factor Nrf2, with concomitant expression of Nrf2-dependent genes. Mechanistically, the HP extract suppressed the ubiquitin-mediated degradation of Nrf2, functioning similarly to a 26S proteasome inhibitor, MG132. Collectively, these results suggest that the HP extract suppresses inflammation in mouse lungs, which is in part related to the HP extract perturbing the ubiquitin-dependent degradation of Nrf2 and thus increasing the function of Nrf2.

Keywords: Anti-Inflammation; Hominis placenta; NF-B; Neutrophilic Inflammation; Nrf2.

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism
  • Female
  • Gene Expression / drug effects
  • HEK293 Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Injections, Intraperitoneal
  • Lipopolysaccharides / adverse effects
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism
  • Neutrophils
  • Placenta*
  • Pneumonia / chemically induced
  • Pneumonia / drug therapy*
  • Pneumonia / metabolism
  • Pregnancy
  • RAW 264.7 Cells
  • Tissue Extracts / administration & dosage
  • Tissue Extracts / pharmacology*
  • Tissue Extracts / therapeutic use*
  • Ubiquitin

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Tissue Extracts
  • Ubiquitin