Jatrorrhizine alleviates cytokine storm secondary lung injury via regulating CD39‐dominant purinergic braking and downstream NLRP3 inflammasome

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Hauptverfasser: Yuejia Lan, Huan Wang, Lijia Jing, Rui Li, Jiayi Sun, Xianli Meng, Jiasi Wu
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Veröffentlicht: Wiley 2025
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author Yuejia Lan
Huan Wang
Lijia Jing
Rui Li
Jiayi Sun
Xianli Meng
Jiasi Wu
author_facet Yuejia Lan
Huan Wang
Lijia Jing
Rui Li
Jiayi Sun
Xianli Meng
Jiasi Wu
Yuejia Lan
Huan Wang
Lijia Jing
Rui Li
Jiayi Sun
Xianli Meng
Jiasi Wu
collection Wiley Open Access
contents Jatrorrhizine alleviates cytokine storm secondary lung injury via regulating CD39‐dominant purinergic braking and downstream NLRP3 inflammasome Yuejia Lan Huan Wang Lijia Jing Rui Li Jiayi Sun Xianli Meng Jiasi Wu Phytotherapy Research AbstractCytokine storm secondary lung injury (CSSLI) is a form of acute lung injury (ALI) comparable to that caused by sepsis for which there are no effective therapeutic strategies. Coptis chinensis Franch. and Scutellaria baicalensis Georgi. are two botanical medicines that exhibit anti‐inflammatory properties. This study aimed to investigate the underlying therapeutic mechanism of the combination (CCSB) treatment in mice with ALI. A high dosage of lipopolysaccharide (LPS) was administered intraperitoneally to C57BL/6 mice to establish an ALI model. The AMP‐Glo™ assay was applied to screen for the component with the most potent CD39‐promoting enzyme activity from CCSB constituents migrating to the bloodstream. The PMA‐differentiated THP‐1 and RAW264.7 macrophage cell lines were stimulated with LPS and adenosine triphosphate, followed by treatment with Jatrorrhizine (JH). The administration of CCSB demonstrated a notable improvement in lung injury through the modulation of the CD39‐P2X7 purinergic pathway and subsequent regulation of the NLRP3 inflammasome. The restrained CD39 and A2b were reversed by JH, leading to the suppression of the P2X7‐NLRP3 signaling pathway. In addition, the utilization of a CD39 inhibitor (POM‐1) attenuated the inhibitory effect of JH on the NLRP3 signaling pathway. CCSB successfully rescued CSSLI, along with its small‐molecule component JH, which demonstrated the ability to inhibit the NLRP3 signaling pathway and pyroptosis, at least partially through regulating the CD39 enzyme. 10.1002/ptr.8062 http://onlinelibrary.wiley.com/termsAndConditions#vor
doi_str_mv 10.1002/ptr.8062
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id wiley_oa_10_1002_ptr_8062
institution Wiley Open Access
license_str_mv http://onlinelibrary.wiley.com/termsAndConditions#vor
publishDate 2025
publisher Wiley
record_format wiley_oa
spellingShingle Jatrorrhizine alleviates cytokine storm secondary lung injury via regulating CD39‐dominant purinergic braking and downstream NLRP3 inflammasome
Yuejia Lan
Huan Wang
Lijia Jing
Rui Li
Jiayi Sun
Xianli Meng
Jiasi Wu
Phytotherapy Research
Jatrorrhizine alleviates cytokine storm secondary lung injury via regulating CD39‐dominant purinergic braking and downstream NLRP3 inflammasome Yuejia Lan Huan Wang Lijia Jing Rui Li Jiayi Sun Xianli Meng Jiasi Wu Phytotherapy Research AbstractCytokine storm secondary lung injury (CSSLI) is a form of acute lung injury (ALI) comparable to that caused by sepsis for which there are no effective therapeutic strategies. Coptis chinensis Franch. and Scutellaria baicalensis Georgi. are two botanical medicines that exhibit anti‐inflammatory properties. This study aimed to investigate the underlying therapeutic mechanism of the combination (CCSB) treatment in mice with ALI. A high dosage of lipopolysaccharide (LPS) was administered intraperitoneally to C57BL/6 mice to establish an ALI model. The AMP‐Glo™ assay was applied to screen for the component with the most potent CD39‐promoting enzyme activity from CCSB constituents migrating to the bloodstream. The PMA‐differentiated THP‐1 and RAW264.7 macrophage cell lines were stimulated with LPS and adenosine triphosphate, followed by treatment with Jatrorrhizine (JH). The administration of CCSB demonstrated a notable improvement in lung injury through the modulation of the CD39‐P2X7 purinergic pathway and subsequent regulation of the NLRP3 inflammasome. The restrained CD39 and A2b were reversed by JH, leading to the suppression of the P2X7‐NLRP3 signaling pathway. In addition, the utilization of a CD39 inhibitor (POM‐1) attenuated the inhibitory effect of JH on the NLRP3 signaling pathway. CCSB successfully rescued CSSLI, along with its small‐molecule component JH, which demonstrated the ability to inhibit the NLRP3 signaling pathway and pyroptosis, at least partially through regulating the CD39 enzyme. 10.1002/ptr.8062 http://onlinelibrary.wiley.com/termsAndConditions#vor
title Jatrorrhizine alleviates cytokine storm secondary lung injury via regulating CD39‐dominant purinergic braking and downstream NLRP3 inflammasome
topic Phytotherapy Research
url https://onlinelibrary.wiley.com/doi/10.1002/ptr.8062