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Article Publish Status: FREE
Abstract Title:

Berberine Attenuates Macrophages Infiltration in Intracranial Aneurysms Potentially Through FAK/Grp78/UPR Axis.

Abstract Source:

Front Pharmacol. 2018 ;9:565. Epub 2018 May 30. PMID: 29899701

Abstract Author(s):

Kai Quan, Sichen Li, Dongdong Wang, Yuan Shi, Zixiao Yang, Jianping Song, Yanlong Tian, Yingjun Liu, Zhiyuan Fan, Wei Zhu

Article Affiliation:

Kai Quan

Abstract:

Inflammatory cells, such as macrophages, play key roles in the pathogenesis of intracranial aneurysms (IAs). Berberine (BBR), an active component of a Chinese herb, 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.Human aneurysm tissues were collected by microsurgical clipping and immunostained for phospho-Focal adhesion kinase (FAK) and CD68macrophages. 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 CD68macrophages 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.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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