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Loureirin B improves H/R-induced hepatic ischemia–reperfusion injury by downregulating ALOX5 to regulate mitochondrial homeostasis

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Abstract

This study was conceived to explore the role and the mechanism of Loureirin B (LB) in hepatic IRI. The viability of LB-treated AML-12 cells was assessed using CCK-8 assay and inflammatory cytokines were detected using ELISA. The activities of ROS and oxidative stress markers MDA, SOD, and GSH-Px were detected using DCFH-DA and corresponding assay kits. The cell apoptosis and caspase3 activity were estimated with flow cytometry and caspase3 assay kits. The expressions of arachidonate 5-lipoxygenase (ALOX5) and apoptosis- and mitochondrial dynamics–related proteins were detected using western blot. The interaction between LB and ALOX5 was analyzed with molecular docking. The transfection efficacy of oe-ALOX5 was examined with RT-qPCR and western blot. Mitochondrial membrane potential was detected with JC-1 staining and immunofluorescence (IF) assay was employed to estimate mitochondrial fusion and fission. The present work found that LB revived the viability, inhibited inflammatory response, suppressed oxidative stress, repressed the apoptosis, and maintained mitochondrial homeostasis in H/R-induced AML-12 cells, which were all reversed by ALOX5 overexpression. Collectively, LB regulated mitochondrial homeostasis by downregulating ALOX5, thereby improving hepatic IRI.

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Authors and Affiliations

  1. Third Department of Internal Medicine, Yiwu Second People’s Hospital, No. 1, Jiangbei Road, Fotang Town, Yiwu, 322000, Zhejiang, China

    Zhaolong Yu

  2. Department of Emergency Medicine, Yiwu Second People’s Hospital, Yiwu, Zhejiang, China

    Shunying Xie

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  1. Zhaolong Yu
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ZLY wrote the main manuscript text and SYX prepared figures 1-6. Both authors reviewed the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Zhaolong Yu.

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Yu, Z., Xie, S. Loureirin B improves H/R-induced hepatic ischemia–reperfusion injury by downregulating ALOX5 to regulate mitochondrial homeostasis. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03079-7

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