18β-Glycyrrhetinic Acid Alleviates P. multocida-Induced Vascular Endothelial Inflammation by PARP1-Mediated NF-κB and HMGB1 Signalling Suppression in PIEC Cells
Qirong Lu,1,* Wantong Han,1,* Defeng Wen,1,* Pu Guo,1 Yu Liu,1 Zhongyuan Wu,1 Shulin Fu,1 Chun Ye,1 Xu Wang,2 Yinsheng Qiu1 1Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, 4...
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Dove Medical Press
2023-06-01
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Series: | Infection and Drug Resistance |
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author | Lu Q Han W Wen D Guo P Liu Y Wu Z Fu S Ye C Wang X Qiu Y |
author_facet | Lu Q Han W Wen D Guo P Liu Y Wu Z Fu S Ye C Wang X Qiu Y |
author_sort | Lu Q |
collection | DOAJ |
description | Qirong Lu,1,* Wantong Han,1,* Defeng Wen,1,* Pu Guo,1 Yu Liu,1 Zhongyuan Wu,1 Shulin Fu,1 Chun Ye,1 Xu Wang,2 Yinsheng Qiu1 1Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, 430023, People’s Republic of China; 2National Reference Laboratory of Veterinary Drug Residues (HZAU) and Ministry of Agriculture Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pu Guo; Yinsheng Qiu, Wuhan Polytechnic University, Wuhan, Hubei, 430023, People’s Republic of China, Email guopu@whpu.edu.cn; qiuyinsheng6405@whpu.edu.cnBackground: At present, the treatment and prevention of Pasteurella multocida infections in pigs mainly rely on antibiotics and vaccines, but inflammatory injury cannot be eliminated. The compound 18β-glycyrrhetinic acid (GA), a pentacyclic triterpenoid extracted from Glycyrrhiza glabra L. root (liquorice) and with a chemical structure similar to that of steroidal hormones, has become a research focus because of its anti-inflammatory, antiulcer, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and neuroprotective effects, but its potential for the treatment of vascular endothelial inflammatory injury by P. multocida infections has not been evaluated. This study aimed to investigate the effects and mechanisms of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections.Materials and Methods: Putative targets of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were identified using network pharmacological screening and molecular docking simulation. The cell viability of PIEC cells was investigated via the CCK-8 assay. The mechanism of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were investigated using cell transfection and western blot.Results: Through network pharmacological screening and molecular docking simulation, this study found that PARP1 may be a core target for GA to exert anti-inflammatory effects. Mechanistically, GA alleviates P. multocida-induced vascular endothelial inflammation by PARP1-mediated NF-κB and HMGB1 signalling suppression.Conclusion: These findings, for the first time, demonstrate the potential therapeutic relationship among GA, PARP1 and inflammatory injury, providing a candidate drug, therapeutic targets and explanation for treating vascular endothelial inflammatory injury caused by P. multocida infection.Keywords: network pharmacology, GA, PARP1, inflammatory injury, P. multocida infection |
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spelling | doaj.art-282033bbab7e4eebb05b310125f84cb32023-07-02T19:49:17ZengDove Medical PressInfection and Drug Resistance1178-69732023-06-01Volume 16420142128479818β-Glycyrrhetinic Acid Alleviates P. multocida-Induced Vascular Endothelial Inflammation by PARP1-Mediated NF-κB and HMGB1 Signalling Suppression in PIEC CellsLu QHan WWen DGuo PLiu YWu ZFu SYe CWang XQiu YQirong Lu,1,* Wantong Han,1,* Defeng Wen,1,* Pu Guo,1 Yu Liu,1 Zhongyuan Wu,1 Shulin Fu,1 Chun Ye,1 Xu Wang,2 Yinsheng Qiu1 1Hubei Key Laboratory of Animal Nutrition and Feed Science, School of Animal Science and Nutritional Engineering, Wuhan Polytechnic University, Wuhan, 430023, People’s Republic of China; 2National Reference Laboratory of Veterinary Drug Residues (HZAU) and Ministry of Agriculture Key Laboratory for the Detection of Veterinary Drug Residues in Foods, Huazhong Agricultural University, Wuhan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pu Guo; Yinsheng Qiu, Wuhan Polytechnic University, Wuhan, Hubei, 430023, People’s Republic of China, Email guopu@whpu.edu.cn; qiuyinsheng6405@whpu.edu.cnBackground: At present, the treatment and prevention of Pasteurella multocida infections in pigs mainly rely on antibiotics and vaccines, but inflammatory injury cannot be eliminated. The compound 18β-glycyrrhetinic acid (GA), a pentacyclic triterpenoid extracted from Glycyrrhiza glabra L. root (liquorice) and with a chemical structure similar to that of steroidal hormones, has become a research focus because of its anti-inflammatory, antiulcer, antimicrobial, antioxidant, immunomodulatory, hepatoprotective and neuroprotective effects, but its potential for the treatment of vascular endothelial inflammatory injury by P. multocida infections has not been evaluated. This study aimed to investigate the effects and mechanisms of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections.Materials and Methods: Putative targets of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were identified using network pharmacological screening and molecular docking simulation. The cell viability of PIEC cells was investigated via the CCK-8 assay. The mechanism of GA intervention in the treatment of vascular endothelial inflammatory injury by P. multocida infections were investigated using cell transfection and western blot.Results: Through network pharmacological screening and molecular docking simulation, this study found that PARP1 may be a core target for GA to exert anti-inflammatory effects. Mechanistically, GA alleviates P. multocida-induced vascular endothelial inflammation by PARP1-mediated NF-κB and HMGB1 signalling suppression.Conclusion: These findings, for the first time, demonstrate the potential therapeutic relationship among GA, PARP1 and inflammatory injury, providing a candidate drug, therapeutic targets and explanation for treating vascular endothelial inflammatory injury caused by P. multocida infection.Keywords: network pharmacology, GA, PARP1, inflammatory injury, P. multocida infectionhttps://www.dovepress.com/18-glycyrrhetinic-acid-alleviates-p-multocida-induced-vascular-endothe-peer-reviewed-fulltext-article-IDRnetwork pharmacologygaparp1inflammatory injuryp. multocida infection |
spellingShingle | Lu Q Han W Wen D Guo P Liu Y Wu Z Fu S Ye C Wang X Qiu Y 18β-Glycyrrhetinic Acid Alleviates P. multocida-Induced Vascular Endothelial Inflammation by PARP1-Mediated NF-κB and HMGB1 Signalling Suppression in PIEC Cells Infection and Drug Resistance network pharmacology ga parp1 inflammatory injury p. multocida infection |
title | 18β-Glycyrrhetinic Acid Alleviates P. multocida-Induced Vascular Endothelial Inflammation by PARP1-Mediated NF-κB and HMGB1 Signalling Suppression in PIEC Cells |
title_full | 18β-Glycyrrhetinic Acid Alleviates P. multocida-Induced Vascular Endothelial Inflammation by PARP1-Mediated NF-κB and HMGB1 Signalling Suppression in PIEC Cells |
title_fullStr | 18β-Glycyrrhetinic Acid Alleviates P. multocida-Induced Vascular Endothelial Inflammation by PARP1-Mediated NF-κB and HMGB1 Signalling Suppression in PIEC Cells |
title_full_unstemmed | 18β-Glycyrrhetinic Acid Alleviates P. multocida-Induced Vascular Endothelial Inflammation by PARP1-Mediated NF-κB and HMGB1 Signalling Suppression in PIEC Cells |
title_short | 18β-Glycyrrhetinic Acid Alleviates P. multocida-Induced Vascular Endothelial Inflammation by PARP1-Mediated NF-κB and HMGB1 Signalling Suppression in PIEC Cells |
title_sort | 18 beta glycyrrhetinic acid alleviates p multocida induced vascular endothelial inflammation by parp1 mediated nf kappa b and hmgb1 signalling suppression in piec cells |
topic | network pharmacology ga parp1 inflammatory injury p. multocida infection |
url | https://www.dovepress.com/18-glycyrrhetinic-acid-alleviates-p-multocida-induced-vascular-endothe-peer-reviewed-fulltext-article-IDR |
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