Evidence map›Paper›PMID 39294398›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2024

Corynoline alleviates hepatic ischemia-reperfusion injury by inhibiting NLRP3 inflammasome activation through enhancing Nrf2/HO-1 signaling.

Xin Ge, Yue Gu, Wendong Wang, Wenzhi Guo, Panliang Wang, Peng Du

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Xin GeDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Yue GuHenan Key Laboratory for Digestive Organ Transplantation, Zhengzhou, Henan Province, China.
Wendong WangDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Wenzhi GuoHenan Key Laboratory for Digestive Organ Transplantation, Zhengzhou, Henan Province, China.
Panliang WangDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. wangpanliang@alumni.sjtu.edu.cn.
Peng DuDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. yzadu1075@163.com.

Funding

Development Programme of Henan Science and Technology Department 222102310201Henan Medical Science and Technology Research Project LHGJ20230188National Natural Science Foundation of China 81900596
6 · The paper itself

Abstract

objectiveCorynoline has displayed pharmacological effects in reducing oxidative stress and inflammatory responses in many disorders. However, its effects on hepatic ischemia-reperfusion (I/R) injury remain unclear. This study aimed to investigate the protective effects of corynoline against hepatic I/R injury and the underlying mechanisms.

methodsRat models with hepatic I/R injury and BRL-3A cell models with hypoxia/reoxygenation (H/R) insult were constructed. Models were pretreated with corynoline and/or other inhibitors for functional and mechanistic examination.

resultsCorynoline pretreatment effectively mitigated hepatic I/R injury verified by reduced serum transaminase levels, improved histological damage scores, and decreased apoptosis rates. Additionally, corynoline pretreatment significantly inhibited I/R-triggered oxidative stress and inflammatory responses, as indicated by enhanced mitochondrial function, reduced levels of ROS and MDA, reduced neutrophil infiltration and suppressed proinflammatory cytokine release. In vitro experiments further showed that corynoline pretreatment increased cellular viability, decreased LDH activity, reduced cellular apoptosis, and inhibited oxidative stress and inflammatory injury in H/R-induced BRL-3A cells. Mechanistically, corynoline significantly increased Nrf2 nuclear translocation and expression levels of its target gene, HO-1. It also blocked NLRP3 inflammasome activation both in vivo and in vitro. Furthermore, pretreatment with Nrf2 inhibitor ML-385 counteracted the protective effect of corynoline on hepatic I/R injury. Ultimately, in vitro studies revealed that the NLRP3 activator nigericin could also nullified the protective effects of corynoline in BRL-3A cells, but had minimal impact on Nrf2 nuclear translocation.

conclusionsCorynoline can exert protective effects against hepatic I/R injury by inhibiting oxidative stress, inflammatory responses, and apoptosis. These effects may be associated with inhibiting ROS-induced NLRP3 inflammasome activation by enhancing Nrf2/HO-1 signaling. These data provide new understanding about the mechanism of corynoline action, suggesting it is a potential drug applied for the treatment and prevention of hepatic I/R injury.

Indexed as

InflammasomesLiverNF-E2-Related Factor 2NLR Family, Pyrin Domain-Containing 3 ProteinRats, Sprague-DawleyReperfusion InjurySignal TransductionAnimalsApoptosisBerberine AlkaloidsCell LineHeme Oxygenase (Decyclizing)MaleOxidative StressRatsBerberine AlkaloidscorynolineHeme Oxygenase (Decyclizing)Hmox1 protein, ratInflammasomesNfe2l2 protein, ratNF-E2-Related Factor 2NLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, ratCorynolineIschemia–reperfusion injuryLiverNLRP3 inflammasomeNrf2

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.