Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR Axis
Background: Inflammatory cells, such as macrophages, play key roles in the pathogenesis of intracranial aneurysms (IAs). Berberine (BBR), an active component of a Chinese herb Coptis chinensis French, has been shown to have anti-inflammatory properties through suppressing macrophage migration in var...
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00565/full |
| _version_ | 1819205749141667840 |
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| author | Kai Quan Sichen Li Dongdong Wang Yuan Shi Zixiao Yang Jianping Song Yanlong Tian Yingjun Liu Zhiyuan Fan Wei Zhu |
| author_facet | Kai Quan Sichen Li Dongdong Wang Yuan Shi Zixiao Yang Jianping Song Yanlong Tian Yingjun Liu Zhiyuan Fan Wei Zhu |
| author_sort | Kai Quan |
| collection | DOAJ |
| description | Background: Inflammatory cells, such as macrophages, play key roles in the pathogenesis of intracranial aneurysms (IAs). Berberine (BBR), an active component of a Chinese herb Coptis chinensis French, has been shown to have anti-inflammatory properties through suppressing macrophage migration in various inflammation animal model. The goal of this study was to examine BBR’s effect on inflammation and IAs formation in a rodent aneurysm model.Methods and Results: Human aneurysm tissues were collected by microsurgical clipping and immunostained for phospho-Focal adhesion kinase (FAK) and CD68+ macrophages. A rodent aneurysm model was induced in 5-week-old male Sprague Dawley (SD) rats by intracranial surgery, then these rats were orally administrated 200 mg/kg/day BBR for 35 days. Immunostaining data showed that BBR inhibited CD68+ macrophages accumulation in IAs tissues and suppressed FAK phosphorylation. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, BBR treatment remarkably attenuated macrophages infiltration, suppressed the expression of matrix metalloproteinases (MMPs), and reduced proinflammatory cytokine secretion, including MCP-1, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-a (TNF-α). Mechanistically, BBR downregulated FAK/Grp78/Unfolded Protein Response (UPR) signaling pathway in RAW264.7 cells.Conclusion: BBR prevents IAs formation potentially through inhibiting FAK phosphorylation and inactivating UPR pathway in macrophages, which causes less macrophage infiltration and reduced proinflammatory cytokine release. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-23T04:56:39Z |
| publishDate | 2018-05-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-8fd74b0b66ad4e8dad12bad85af52e072022-12-21T17:59:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-05-01910.3389/fphar.2018.00565354647Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR AxisKai Quan0Sichen Li1Dongdong Wang2Yuan Shi3Zixiao Yang4Jianping Song5Yanlong Tian6Yingjun Liu7Zhiyuan Fan8Wei Zhu9Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Radiology, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, ChinaBackground: Inflammatory cells, such as macrophages, play key roles in the pathogenesis of intracranial aneurysms (IAs). Berberine (BBR), an active component of a Chinese herb Coptis chinensis French, has been shown to have anti-inflammatory properties through suppressing macrophage migration in various inflammation animal model. The goal of this study was to examine BBR’s effect on inflammation and IAs formation in a rodent aneurysm model.Methods and Results: Human aneurysm tissues were collected by microsurgical clipping and immunostained for phospho-Focal adhesion kinase (FAK) and CD68+ macrophages. A rodent aneurysm model was induced in 5-week-old male Sprague Dawley (SD) rats by intracranial surgery, then these rats were orally administrated 200 mg/kg/day BBR for 35 days. Immunostaining data showed that BBR inhibited CD68+ macrophages accumulation in IAs tissues and suppressed FAK phosphorylation. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, BBR treatment remarkably attenuated macrophages infiltration, suppressed the expression of matrix metalloproteinases (MMPs), and reduced proinflammatory cytokine secretion, including MCP-1, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-a (TNF-α). Mechanistically, BBR downregulated FAK/Grp78/Unfolded Protein Response (UPR) signaling pathway in RAW264.7 cells.Conclusion: BBR prevents IAs formation potentially through inhibiting FAK phosphorylation and inactivating UPR pathway in macrophages, which causes less macrophage infiltration and reduced proinflammatory cytokine release.https://www.frontiersin.org/article/10.3389/fphar.2018.00565/fullBerberineFocal adhesion kinaseendoplasmic reticulum stressintracranial aneurysmmacrophage |
| spellingShingle | Kai Quan Sichen Li Dongdong Wang Yuan Shi Zixiao Yang Jianping Song Yanlong Tian Yingjun Liu Zhiyuan Fan Wei Zhu Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR Axis Frontiers in Pharmacology Berberine Focal adhesion kinase endoplasmic reticulum stress intracranial aneurysm macrophage |
| title | Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR Axis |
| title_full | Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR Axis |
| title_fullStr | Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR Axis |
| title_full_unstemmed | Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR Axis |
| title_short | Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR Axis |
| title_sort | berberine attenuates macrophages infiltration in intracranial aneurysms potentially through fak grp78 upr axis |
| topic | Berberine Focal adhesion kinase endoplasmic reticulum stress intracranial aneurysm macrophage |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00565/full |
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