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.
Keywords: Carbapenem-resistant Klebsiella pneumoniae; Glycyrrhetinic acid; Inflammation; Nrf-2; Oxidative stress.
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