AUTHOR=Quan Kai , Li Sichen , Wang Dongdong , Shi Yuan , Yang Zixiao , Song Jianping , Tian Yanlong , Liu Yingjun , Fan Zhiyuan , Zhu Wei
TITLE=Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR Axis
JOURNAL=Frontiers in Pharmacology
VOLUME=9
YEAR=2018
URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00565
DOI=10.3389/fphar.2018.00565
ISSN=1663-9812
ABSTRACT=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.