Bergapten attenuates hemorrhagic shock induced multi-organ injury by inhibiting NLRP3 inflammasome activation and pyroptosis.

Autor: Rao T; Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou, China., Yang W; Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou, China., Ma X; Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou, China., Jiang X; Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou, China., Jiang S; Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou, China. Electronic address: jansoean@zju.edu.cn., Xu S; Department of Emergency Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Key Laboratory of The Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province, Hangzhou, China; Zhejiang Provincial Clinical Research Center for Emergency and Critical Care Medicine, Hangzhou, China. Electronic address: 2201027@zju.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Oct 25; Vol. 140, pp. 112839. Date of Electronic Publication: 2024 Aug 09.
DOI: 10.1016/j.intimp.2024.112839
Abstrakt: Objectives: Treatment of hemorrhagic shock (HS) induced multi-organ injury remains a challenge. Bergapten (BeG) is a bioactive coumarin-derived compound, and previous articles have suggested that BeG may serve as a prospective therapeutic modality for HS. This study was designed to investigate the efficacy of BeG in the treatment of HS and its underlying mechanisms.
Methods: In this research, we established a rat model of HS, following which we assessed the protective effects of BeG on HS induced multi-organ injury. Subsequently, we scrutinized the activation of NLRP3 inflammasomes and pyroptosis in damaged organs. Additionally, we conducted examinations of AMPK and the downstream mitophagy pathway in damaged organs. Finally, we established a hypoxia/reoxygenation (H/R) model in HK-2 cells to simulate the in vitro HS process. Following AMPK inhibition with compound C, we evaluated the levels of mitophagy and cellular pyroptosis in BeG-treated HK-2 cells subjected to H/R.
Results: BeG treatment alleviated HS induced multi-organ injury. Subsequent analyses indicated that the therapeutic effects of BeG were related to the attenuation of NLRP3 inflammasome activation and pyroptosis. Additionally, we found BeG treatment stimulated the phosphorylation of AMPK, thereby enhancing mitophagy. Lastly, we found that the inhibition of AMPK in vitro attenuates BeG's enhancement of mitophagy and its suppression of pyroptosis.
Conclusion: Our research indicates that BeG has the potential to alleviate multi-organ injury induced by HS. The protective effect of BeG is likely associated with its promotion of mitophagy through AMPK activation, thereby inhibiting NLRP3 inflammasome-mediated pyroptosis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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