18β-Glycyrrhetinic acid protectes neonatal rats with hyperoxia exposure
through inhibiting ROS/NF-κB/NLRP3 inflammasome
Abstract
Bronchopulmonary dysplasia (BPD) is a common devastating pulmonary
complication in preterm infants. Oxygen supplementation is a lifesaving
therapeutic measure used for premature infants with pulmonary
insufficiency. However, oxygen toxicity is a significant trigger for
BPD, and oxidative stress-induced inflammatory responses, in turn,
worsens the oxidative toxicity resulting in lung injury and arresting of
lung development. Glycyrrhiza radix is commonly used in the medicine and
food industries. 18β-Glycyrrhetinic acid (18β-GA), a primary active
ingredient of Glycyrrhiza radix, has a powerful anti-oxidative and
anti-inflammatory effects. This study aimed to determine whether 18β-GA
has protective effects 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 weights 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 exposure increased ROS
level and pulmonary inflammation, and activated NF-κB and the NLRP3
inflammasome. 18β-GA treatment decreased ROS level, inhibited the
activation of NF-κB and the NLRP3 inflammasome, decreased pulmonary
inflammation, improved alveolar development, and increased the
bodyweight of neonatal rats with hyperoxia exposure. Our study
demonstrates that 18β-GA protects neonatal rats with hyperoxia exposure
through inhibiting ROS/NF-κB/NLRP3 inflammasome.