Glycyrrhetinic acid prevents carbapenem-resistant Klebsiella pneumoniae-induced cell injury by inhibiting mitochondrial dysfunction via Nrf-2 pathway.

Abstract

OBJECTIVES:

Due to the abuse of antibiotics, the high reoccurrence of drug-resistance strains, such as carbapenem-resistant Klebsiella pneumoniae (CRKP), deteriorates CRKP-infected pneumonia in the clinic, suggesting it is necessary to find new alternatives. Glycyrrhetinic acid (GA), an active ingredient of Yinhuapinggan granule, has antioxidant & anti-inflammatory capacity. Little, however, is known about the effects of GA on CRKP-induced epithelial injury.

METHODS:

In this research, we examined the protective effects of GA against pulmonary epithelium damage caused by CRKP infection and potential molecular mechanisms.

RESULTS:

Our results noted GA significantly promoted cell survival and reduced pro-inflammatory cytokines production, during CRKP-induced human pulmonary epithelial cell. Mechanically, GA alleviated mitochondrial-damage-induced apoptosis amid CRKP infection by inhibiting mitochondrial damage. Additionally, we found GA inhibited the expression of pro-apoptotic proteins Cyto-c, the Bax, and Caspase-3 while increasing the expression of anti-apoptotic protein Bcl-2. Further exploration found GA could trigger Nrf-2 expression at both gene and protein levels, activating antioxidative proteins to diminish CRKP-induced oxidative stress.

CONCLUSION:

Together, our results demonstrated that GA was a promising candidate to alleviate CRKP-infected lung injury as well as a synergist to treat CRKP infection with antibiotics.

• Authors: Xiaodan Guan, Liang Jin, Daojun Yu, Yu He, Yida Bao, Huifen Zhou, Haitong Wan
• Journal: Microbial pathogenesis (Microb Pathog) Vol. 177 Pg. 105825 (Apr 2023) ISSN: 1096-1208 [Electronic] England
• PMID: 36244594 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Glycyrrhetinic Acid
• Anti-Bacterial Agents
• Carbapenems

Topics

• Humans
• Klebsiella pneumoniae
• Glycyrrhetinic Acid (pharmacology)
• Klebsiella Infections (drug therapy)
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Carbapenems (pharmacology)
• Carbapenem-Resistant Enterobacteriaceae
• Mitochondria
• Drug Resistance, Bacterial