Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling Pathway
Background: Liquiritin (LIQ) is a traditional Chinese medicine that has been reported to regulate inflammation, oxidative stress and cell apoptosis. However, the beneficial effects of LIQ in lipopolysaccharides (LPS)-induced septic cardiomyopathy (SCM) has not been reported. The primary goal of this...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.648688/full |
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| author | Shan-Qi Mou Shan-Qi Mou Shan-Qi Mou Zi-Ying Zhou Zi-Ying Zhou Zi-Ying Zhou Hong Feng Nan Zhang Nan Zhang Nan Zhang Zheng Lin Zheng Lin Zheng Lin Xiahenazi Aiyasiding Xiahenazi Aiyasiding Xiahenazi Aiyasiding Wen-Jing Li Wen-Jing Li Wen-Jing Li Wen Ding Wen Ding Wen Ding Hai-Han Liao Hai-Han Liao Hai-Han Liao Zhou-Yan Bian Zhou-Yan Bian Zhou-Yan Bian Qi-Zhu Tang Qi-Zhu Tang Qi-Zhu Tang |
| author_facet | Shan-Qi Mou Shan-Qi Mou Shan-Qi Mou Zi-Ying Zhou Zi-Ying Zhou Zi-Ying Zhou Hong Feng Nan Zhang Nan Zhang Nan Zhang Zheng Lin Zheng Lin Zheng Lin Xiahenazi Aiyasiding Xiahenazi Aiyasiding Xiahenazi Aiyasiding Wen-Jing Li Wen-Jing Li Wen-Jing Li Wen Ding Wen Ding Wen Ding Hai-Han Liao Hai-Han Liao Hai-Han Liao Zhou-Yan Bian Zhou-Yan Bian Zhou-Yan Bian Qi-Zhu Tang Qi-Zhu Tang Qi-Zhu Tang |
| author_sort | Shan-Qi Mou |
| collection | DOAJ |
| description | Background: Liquiritin (LIQ) is a traditional Chinese medicine that has been reported to regulate inflammation, oxidative stress and cell apoptosis. However, the beneficial effects of LIQ in lipopolysaccharides (LPS)-induced septic cardiomyopathy (SCM) has not been reported. The primary goal of this study was to investigate the effects of LIQ in LPS-induced SCM model.Methods: Mice were pre-treated with LIQ for 7 days before they were injected with LPS (10 mg/kg) for inducing SCM model. Echocardiographic analysis was used to evaluate cardiac function after 12 h of LPS injection. Thereafter, mice were sacrificed to collect hearts for molecular and histopathologic assays by RT-PCR, western-blots, immunohistochemical and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining analysis respectively. AMPKα2 knockout (AMPKα2−/−) mice were used to elucidate the mechanism of LIQ Neonatal rat cardiomyocytes (NRCMs) treated with or without LPS were used to further investigate the roles and mechanisms of LIQ in vitro experiments.Results: LIQ administration attenuated LPS-induced mouse cardiac dysfunction and reduced mortality, based upon the restoration of EF, FS, LVEDs, heart rate, dp/dt max and dp/dt min deteriorated by LPS treatment. LIQ treatment also reduced mRNA expression of TNFα, IL-6 and IL-1β, inhibited inflammatory cell migration, suppressed cardiac oxidative stress and apoptosis, and improved metabolism. Mechanistically, LIQ enhanced the phosphorylation of AMP-activated protein kinase α2 (AMPKα2) and decreased the phosphorylation of mTORC1, IκBα and NFκB/p65. Importantly, the beneficial roles of LIQ were not observed in AMPKα2 knockout model, nor were they observed in vitro model after inhibiting AMPK activity with an AMPK inhibitor.Conclusion: We have demonstrated that LIQ exerts its protective effects in an SCM model induced by LPS administration. LIQ reduced inflammation, oxidative stress, apoptosis and metabolic alterations via regulating AMPKα2 dependent signaling pathway. Thus, LIQ might be a potential treatment or adjuvant for SCM treatment. |
| first_indexed | 2024-12-20T00:15:26Z |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T00:15:26Z |
| publishDate | 2021-05-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-5efc968362fc4781b12131305384243a2022-12-21T20:00:23ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.648688648688Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling PathwayShan-Qi Mou0Shan-Qi Mou1Shan-Qi Mou2Zi-Ying Zhou3Zi-Ying Zhou4Zi-Ying Zhou5Hong Feng6Nan Zhang7Nan Zhang8Nan Zhang9Zheng Lin10Zheng Lin11Zheng Lin12Xiahenazi Aiyasiding13Xiahenazi Aiyasiding14Xiahenazi Aiyasiding15Wen-Jing Li16Wen-Jing Li17Wen-Jing Li18Wen Ding19Wen Ding20Wen Ding21Hai-Han Liao22Hai-Han Liao23Hai-Han Liao24Zhou-Yan Bian25Zhou-Yan Bian26Zhou-Yan Bian27Qi-Zhu Tang28Qi-Zhu Tang29Qi-Zhu Tang30Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaDepartment of Geriatrics, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, ChinaBackground: Liquiritin (LIQ) is a traditional Chinese medicine that has been reported to regulate inflammation, oxidative stress and cell apoptosis. However, the beneficial effects of LIQ in lipopolysaccharides (LPS)-induced septic cardiomyopathy (SCM) has not been reported. The primary goal of this study was to investigate the effects of LIQ in LPS-induced SCM model.Methods: Mice were pre-treated with LIQ for 7 days before they were injected with LPS (10 mg/kg) for inducing SCM model. Echocardiographic analysis was used to evaluate cardiac function after 12 h of LPS injection. Thereafter, mice were sacrificed to collect hearts for molecular and histopathologic assays by RT-PCR, western-blots, immunohistochemical and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining analysis respectively. AMPKα2 knockout (AMPKα2−/−) mice were used to elucidate the mechanism of LIQ Neonatal rat cardiomyocytes (NRCMs) treated with or without LPS were used to further investigate the roles and mechanisms of LIQ in vitro experiments.Results: LIQ administration attenuated LPS-induced mouse cardiac dysfunction and reduced mortality, based upon the restoration of EF, FS, LVEDs, heart rate, dp/dt max and dp/dt min deteriorated by LPS treatment. LIQ treatment also reduced mRNA expression of TNFα, IL-6 and IL-1β, inhibited inflammatory cell migration, suppressed cardiac oxidative stress and apoptosis, and improved metabolism. Mechanistically, LIQ enhanced the phosphorylation of AMP-activated protein kinase α2 (AMPKα2) and decreased the phosphorylation of mTORC1, IκBα and NFκB/p65. Importantly, the beneficial roles of LIQ were not observed in AMPKα2 knockout model, nor were they observed in vitro model after inhibiting AMPK activity with an AMPK inhibitor.Conclusion: We have demonstrated that LIQ exerts its protective effects in an SCM model induced by LPS administration. LIQ reduced inflammation, oxidative stress, apoptosis and metabolic alterations via regulating AMPKα2 dependent signaling pathway. Thus, LIQ might be a potential treatment or adjuvant for SCM treatment.https://www.frontiersin.org/articles/10.3389/fphar.2021.648688/fullliquiritinAMPKαseptic cardiomyopathyinflammationapoptosis |
| spellingShingle | Shan-Qi Mou Shan-Qi Mou Shan-Qi Mou Zi-Ying Zhou Zi-Ying Zhou Zi-Ying Zhou Hong Feng Nan Zhang Nan Zhang Nan Zhang Zheng Lin Zheng Lin Zheng Lin Xiahenazi Aiyasiding Xiahenazi Aiyasiding Xiahenazi Aiyasiding Wen-Jing Li Wen-Jing Li Wen-Jing Li Wen Ding Wen Ding Wen Ding Hai-Han Liao Hai-Han Liao Hai-Han Liao Zhou-Yan Bian Zhou-Yan Bian Zhou-Yan Bian Qi-Zhu Tang Qi-Zhu Tang Qi-Zhu Tang Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling Pathway Frontiers in Pharmacology liquiritin AMPKα septic cardiomyopathy inflammation apoptosis |
| title | Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling Pathway |
| title_full | Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling Pathway |
| title_fullStr | Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling Pathway |
| title_full_unstemmed | Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling Pathway |
| title_short | Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling Pathway |
| title_sort | liquiritin attenuates lipopolysaccharides induced cardiomyocyte injury via an amp activated protein kinase dependent signaling pathway |
| topic | liquiritin AMPKα septic cardiomyopathy inflammation apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.648688/full |
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