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Published on: January 4, 2019
Chlorogenic acid inhibits macrophage PANoptosis induced by cefotaxime-resistant Escherichia coli
Chunxiu Lu1, Liang Jin1,2, Huifen Zhou1
1School of Life Sciences, Zhejiang Chinese Medical University, No. 548, Binwen Road, Binjiang District, Hangzhou, 310053, Zhejiang, People's Republic of China.
Abstract:
Antibiotics are commonly used in clinical practice to treat bacterial infections. Due to the abuse of antibiotics, the emergence of drug-resistant strains, such as cefotaxime sodium-resistant Escherichia coli (CSR-EC), has aggravated the treatment of diseases caused by bacterial infections in the clinic. Therefore, discovering new drug candidates with unique mechanisms of action is imperative. Chlorogenic acid (CGA) is an active component of Yinhua Pinggan Granule, which has antioxidant and anti-inflammatory effects. We chose the CGA to explore its effects on PANoptosis in cultured macrophages infected with CSR-EC. In this study, we explored the protective impact of CGA on macrophage cell damage generated by CSR-EC infection and the potential molecular mechanistic consequences of post-infection therapy with CGA on the PANoptosis pathway. Our findings demonstrated that during CSR-EC-induced macrophage infection, CGA dramatically increased cell survival. CGA can inhibit pro-inflammatory cytokine expression of IL-1β, IL-18, TNF-α, and IL-6. CGA decreased ROS generation and increased Nrf-2 expression at the gene and protein levels to lessen the cell damage and death brought on by CSR-EC infection. Additionally, we discovered that the proteins Caspase-3, Caspase-7, Caspase-8, Caspase-1, GSDMD, NLRP-3, RIPK-3, and MLKL were all inhibited by CGA. In summary, our research suggests that CGA is a contender for reducing lesions brought on by CSR-EC infections and that it can work in concert with antibiotics to treat CSR-EC infections clinically. However, further research on its mechanism of action is still needed.
Insights
Chlorogenic acid (CGA) protects macrophages from cefotaxime sodium-resistant Escherichia coli (CSR-EC) infection by inhibiting PANoptosis and reducing inflammation. CGA shows potential as a therapeutic agent against drug-resistant bacterial infections.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Antibiotic resistance, exemplified by cefotaxime sodium-resistant Escherichia coli (CSR-EC), poses a significant clinical challenge.
- Discovering novel therapeutic agents with unique mechanisms is crucial for combating resistant bacterial infections.
- Chlorogenic acid (CGA), known for antioxidant and anti-inflammatory properties, is investigated for its potential in treating bacterial infections.
Purpose of the Study:
- To investigate the protective effects of Chlorogenic acid (CGA) against CSR-EC-induced damage in cultured macrophages.
- To elucidate the molecular mechanisms underlying CGA's action, particularly its impact on the PANoptosis pathway.
Main Methods:
- Macrophage cell cultures were infected with CSR-EC.
- The effects of CGA treatment on cell survival, pro-inflammatory cytokine expression (IL-1β, IL-18, TNF-α, IL-6), reactive oxygen species (ROS) generation, and Nrf-2 expression were assessed.
- The impact of CGA on key proteins in the PANoptosis pathway (Caspase-3, -7, -8, -1, GSDMD, NLRP-3, RIPK-3, MLKL) was evaluated.
Main Results:
- CGA significantly enhanced macrophage survival during CSR-EC infection.
- CGA suppressed the expression of pro-inflammatory cytokines and reduced ROS generation.
- CGA upregulated Nrf-2 expression and inhibited key proteins involved in the PANoptosis pathway.
Conclusions:
- Chlorogenic acid (CGA) demonstrates significant protective effects against CSR-EC-induced macrophage damage by modulating the PANoptosis pathway.
- CGA's anti-inflammatory and antioxidant properties contribute to its therapeutic potential.
- CGA may serve as a valuable adjunct therapy in treating infections caused by drug-resistant bacteria like CSR-EC.
