Protective Effects of 18β-Glycyrrhetinic Acid on Neonatal Rats with Hyperoxia Exposure

Inflammation. 2022 Jun;45(3):1224-1238. doi: 10.1007/s10753-021-01616-7. Epub 2022 Jan 6.

Abstract

Bronchopulmonary dysplasia (BPD) is a common devastating pulmonary complication in preterm infants. Supplemental oxygen is a lifesaving therapeutic measure used for premature infants with pulmonary insufficiency. However, oxygen toxicity is a significant trigger for BPD. Oxidative stress disrupts lung development, accompanied by increased pro-inflammatory cytokines and chemokines expression and immune cells infiltration in lung tissue. Licorice, a typical traditional herbal medicine, is commonly used in the medicine and food industries. 18β-Glycyrrhetinic acid (18β-GA), a primary active ingredient of licorice, has powerful anti-oxidative and anti-inflammatory effects. This study aimed to determine whether 18β-GA has a protective effect on neonatal rats with hyperoxia exposure. Newborn Sprague-Dawley rats were kept in either 21% (normoxia) or 80% O2 (hyperoxia) continuously from postnatal day (PN) 1 to 14. 18β-GA was injected intragastrically at 50 or 100 mg/kg body weight once a day from PN 1 to 14. We examined the body weight and alveolar development and measured ROS level and the markers of pulmonary inflammation. Mature-IL-1β and NF-κB pathway proteins, and the NLRP3 inflammasome, were assessed; concurrently, caspase-1 activity was measured. Our results indicated that hyperoxia resulted in alveolar simplification and decreased bodyweight of neonatal rats. Hyperoxia increased ROS level and pulmonary inflammation and activated NF-κB and the NLRP3 inflammasome. 18β-GA treatment inhibited the activation of NF-κB and the NLRP3 inflammasome, decreased ROS level and pulmonary inflammation, improved alveolar development, and increased the bodyweight of neonatal rats with hyperoxia exposure. Our study demonstrates that 18β-GA has a protective effect on neonatal rats with hyperoxia exposure.

Keywords: 18β-Glycyrrhetinic acid; Alveolarization; Bronchopulmonary dysplasia; Inflammation; NF-κB pathway; NLRP3 inflammasome; Reactive oxygen species.

MeSH terms

  • Animals
  • Animals, Newborn
  • Body Weight
  • Bronchopulmonary Dysplasia* / drug therapy
  • Bronchopulmonary Dysplasia* / prevention & control
  • Glycyrrhetinic Acid / analogs & derivatives
  • Humans
  • Hyperoxia* / complications
  • Infant, Newborn
  • Infant, Premature
  • Inflammasomes / metabolism
  • Lung / metabolism
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Oxygen / pharmacology
  • Pneumonia*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / pharmacology

Substances

  • Inflammasomes
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Reactive Oxygen Species
  • 18alpha-glycyrrhetinic acid
  • Glycyrrhetinic Acid
  • Oxygen