Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB Pathway
Increasing evidence shows that inflammation plays a vital role in the occurrence and development of ischemia/reperfusion (I/R). Suppression of excessive inflammation can ameliorate impaired cardiac function, which shows therapeutic potential for clinical treatment of myocardial ischemia/reperfusion...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-02-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2018.00109/full |
| _version_ | 1818041319622180864 |
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| author | Rui Zhang Dan Han Zhenyu Li Chengwu Shen Yahui Zhang Jun Li Genquan Yan Shasha Li Bo Hu Jiangbing Li Ping Liu |
| author_facet | Rui Zhang Dan Han Zhenyu Li Chengwu Shen Yahui Zhang Jun Li Genquan Yan Shasha Li Bo Hu Jiangbing Li Ping Liu |
| author_sort | Rui Zhang |
| collection | DOAJ |
| description | Increasing evidence shows that inflammation plays a vital role in the occurrence and development of ischemia/reperfusion (I/R). Suppression of excessive inflammation can ameliorate impaired cardiac function, which shows therapeutic potential for clinical treatment of myocardial ischemia/reperfusion (MI/R) diseases. In this study, we investigated whether Ginkgolide C (GC), a potent anti-inflammatory flavone, extenuated MI/R injury through inhibition of inflammation. In vivo, rats with the occlusion of the left anterior descending (LAD) coronary artery were applied to mimic MI/R injury. In vitro, primary cultured neonatal ventricular myocytes exposed to hypoxia/reoxygenation (H/R) were applied to further discuss the anti-H/R injury property of GC. The results revealed that GC significantly improved the symptoms of MI/R injury, as evidenced by reducing infarct size, preventing myofibrillar degeneration and reversing the mitochondria dysfunction. Moreover, histological analysis and Myeloperoxidase (MPO) activity measurement showed that GC remarkably suppressed Polymorphonuclears (PMNs) infiltration and ameliorated the histopathological damage. Furthermore, GC pretreatment was shown to improve H/R-induced ventricular myocytes viability and enhance tolerance of inflammatory insult, as evidenced by suppressing expression of CD40, translocation of NF-κB p65 subunit, phosphorylation of IκB-α, as well as the activity of IKK-β. In addition, downstream inflammatory cytokines modulated by NF-κB signaling were effectively down-regulated both in vivo and in vitro, as determined by immunohistochemistry and ELISA. In conclusion, these results indicate that GC possesses a beneficial effect against MI/R injury via inflammation inhibition that may involve suppression of CD40-NF-κB signal pathway and downstream inflammatory cytokines expression, which may offer an alternative medication for MI/R diseases. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T08:28:32Z |
| publishDate | 2018-02-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-f247a34cbcc84ec3bdb778d7e3b34dc22022-12-22T01:56:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-02-01910.3389/fphar.2018.00109327207Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB PathwayRui Zhang0Dan Han1Zhenyu Li2Chengwu Shen3Yahui Zhang4Jun Li5Genquan Yan6Shasha Li7Bo Hu8Jiangbing Li9Ping Liu10Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, ChinaDepartment of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaMinimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaDepartment of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, ChinaIncreasing evidence shows that inflammation plays a vital role in the occurrence and development of ischemia/reperfusion (I/R). Suppression of excessive inflammation can ameliorate impaired cardiac function, which shows therapeutic potential for clinical treatment of myocardial ischemia/reperfusion (MI/R) diseases. In this study, we investigated whether Ginkgolide C (GC), a potent anti-inflammatory flavone, extenuated MI/R injury through inhibition of inflammation. In vivo, rats with the occlusion of the left anterior descending (LAD) coronary artery were applied to mimic MI/R injury. In vitro, primary cultured neonatal ventricular myocytes exposed to hypoxia/reoxygenation (H/R) were applied to further discuss the anti-H/R injury property of GC. The results revealed that GC significantly improved the symptoms of MI/R injury, as evidenced by reducing infarct size, preventing myofibrillar degeneration and reversing the mitochondria dysfunction. Moreover, histological analysis and Myeloperoxidase (MPO) activity measurement showed that GC remarkably suppressed Polymorphonuclears (PMNs) infiltration and ameliorated the histopathological damage. Furthermore, GC pretreatment was shown to improve H/R-induced ventricular myocytes viability and enhance tolerance of inflammatory insult, as evidenced by suppressing expression of CD40, translocation of NF-κB p65 subunit, phosphorylation of IκB-α, as well as the activity of IKK-β. In addition, downstream inflammatory cytokines modulated by NF-κB signaling were effectively down-regulated both in vivo and in vitro, as determined by immunohistochemistry and ELISA. In conclusion, these results indicate that GC possesses a beneficial effect against MI/R injury via inflammation inhibition that may involve suppression of CD40-NF-κB signal pathway and downstream inflammatory cytokines expression, which may offer an alternative medication for MI/R diseases.http://journal.frontiersin.org/article/10.3389/fphar.2018.00109/fullginkgolide Cmyocardial ischemia/reperfusion injuryinflammationCD40NF-κB |
| spellingShingle | Rui Zhang Dan Han Zhenyu Li Chengwu Shen Yahui Zhang Jun Li Genquan Yan Shasha Li Bo Hu Jiangbing Li Ping Liu Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB Pathway Frontiers in Pharmacology ginkgolide C myocardial ischemia/reperfusion injury inflammation CD40 NF-κB |
| title | Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB Pathway |
| title_full | Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB Pathway |
| title_fullStr | Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB Pathway |
| title_full_unstemmed | Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB Pathway |
| title_short | Ginkgolide C Alleviates Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Inhibition of CD40-NF-κB Pathway |
| title_sort | ginkgolide c alleviates myocardial ischemia reperfusion induced inflammatory injury via inhibition of cd40 nf κb pathway |
| topic | ginkgolide C myocardial ischemia/reperfusion injury inflammation CD40 NF-κB |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2018.00109/full |
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