Protective Effects of Rhamnetin in Carbapenem-Resistant <i>Acinetobacter baumannii</i>-Induced Sepsis Model and the Underlying Mechanism
Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) is a well-known harmful bacterium that causes severe health disorders and dysregulates the host immune response associated with inflammation. Upon examining the suppressive activity of natural flavonoid rhamnetin on various pro-i...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/21/15603 |
| Summary: | Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) is a well-known harmful bacterium that causes severe health disorders and dysregulates the host immune response associated with inflammation. Upon examining the suppressive activity of natural flavonoid rhamnetin on various pro-inflammatory cytokines in a CRAB-induced septic shock mouse model, we found that rhamnetin inhibited the production of IL-1β and IL-18, two pro-inflammatory cytokines associated with pyroptotic cell death, a process dependent on caspase-1. In this study, we investigated the antioxidant and anti-apoptotic activities of rhamnetin and the underlying mechanism of action in a CRAB infection. In the CRAB-induced septic shock mouse model, rhamnetin reduced the level of lipopolysaccharide (LPS) in lung lysates, resulting in the inhibition of TLR4-mediated inflammatory signaling. Notably, rhamnetin reduced intracellular reactive oxygen species (ROS) generation in macrophages and inhibited apoptotic and pyroptotic cell injury induced by CRAB infection. Therefore, rhamnetin inhibited LPS-induced pro-inflammatory mediators, hindering apoptotic and pyroptotic processes and contributing to a recovery effect in CRAB-induced sepsis mice by suppressing oxidative stress. Taken together, our study presents the potential role of rhamnetin in protecting against oxidative damage induced by CRAB infection through a TLR4 and ROS-mediated pyroptotic pathway, showing an alternative mechanism for sepsis prevention. Therefore, rhamnetin is a promising therapeutic candidate for treating CRAB-induced sepsis. |
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| ISSN: | 1661-6596 1422-0067 |