Glycyrrhetinic acid protects against Multidrug-resistant Acinetobacter baumannii-induced lung epithelial cells injury by regulating inflammation and oxidative stress

Abstract

Glycyrrhetinic acid (GA) is a bio-effective component of Licorice. The GA is a monomer and the ingredient is an Oleanane-type pentacyclic triterpenes that has been used as a remedy for years. Due to the abuse of antibiotics, people pay attention to the emergence of Multidrug-resistant Acinetobacter baumannii (MDR-AB). As a conditional pathogen, MDR-AB causes severe infection, endangering human lives. Our previous studies found GA played an important role in Yinhua Pinggan, a Chinese medicine. However, whether GA could protect lung epithelium from MDR-AB-induced cell injury was elusive. Herein, we investigated the effects of GA on MDR-AB-infected A549 cells. The results showed GA had slightly antibacterial activity to MDR-AB in the GA (high concentration) but no impact on drug resistance genes. Notwithstanding, GA could reverse MDR-AB-induced cell apoptosis, hampered adhesion and invasion of MDR-AB to cells, and inhibit pro-inflammatory cytokines expression of IL-1β, IL-6, and TNF. Besides, MDR-AB-induced reactive oxygen species, pro-oxidative protein malonaldehyde, and myeloperoxidase of cells were decreased by GA, while antioxidative proteins were recovered, showing antioxidative capacity of GA might play a critical role. The expressions of toll-like receptor (TLRs) - 1, 2, 4, 5, 6, and 9 were increased by MDR-AB infection, while GA reversed the tendency. Interestingly, GA inhibited MDR-AB induced myeloiddifferentiationfactor88 expression (MYD88), one downstream con-factors of TLRs, but no affection on Interferon regulatory Factor 3 (IRF3), the other one, indicating GA inhibited MDR-AB induced cell injury by impact TLR/MYD88 pathway to attenuate inflammation. Altogether, our results demonstrated that GA protects against MDR-AB-induced cell injury through its antioxidative and anti-inflammatory properties, which deserve further study in the future.

Exploring Beta-Lactamase Inhibitory Potential of Common Medicinal Plants

“…Guan et al (2023) has reported that Glycyrrhetinic acid not only shows anti-inflammatory activities but is also able to inhibit the growth of carbapenem-resistant K. pneumoniae. Other studies have also confirmed that Glycyrrhetinic acid can provide protection against Acinetobacter baumannii and P. aeruginosa induced nosocomial infections (Carruthers et al, 2020;Guo et al, 2023).…”

Protective Effects of Rhamnetin in Carbapenem-Resistant Acinetobacter baumannii-Induced Sepsis Model and the Underlying Mechanism

“…Various reports have shown that LPS, an endotoxin produced by Gram-negative bacteria, exerts severe oxidative stress on macrophages owing to excessive ROS production, which activates the inflammatory signaling cascade. Recently, it was discovered that MDR A. baumannii invasion causes lung epithelial cell injury owing to oxidative stress triggered by ROS generation [39]. Therefore, we suspected that the macrophage cell damage caused by CRAB infection may be due to ROS production.…”

Polydatin prevent lung epithelial cell from Carbapenem-resistant Klebsiella pneumoniae injury by inhibiting biofilm formation and oxidative stress

“…1 A) 9 – 11 . PD is also an important component of traditional Chinese medicine compounds, Yinhuapinggan (YHPG) granules used to treat respiratory infections 12 – 16 . YHPG was composed of six herbs, which had the effect of clearing heat and detoxifying 17 .…”