泡葉藻和墨角藻藉由調節炎症和 PTEN/PI3K/AKT 信號傳遞路徑以改善血管再狹窄

TMUIR > College of Pharmacy > Ph. D. Program for the Clinical Drug Discovery from Botanical Herbs > Dissertations/Theses > Item 987654321/62904

Please use this identifier to cite or link to this item: http://libir.tmu.edu.tw/handle/987654321/62904

Title:	泡葉藻和墨角藻藉由調節炎症和 PTEN/PI3K/AKT 信號傳遞路徑以改善血管再狹窄 Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signalling pathway
Authors:	ZUMBI, CRYSTAL NGOFI
Contributors:	中草藥臨床藥物研發博士學位學程 WU, CHIEH-HSI
Keywords:	Ascophyllum nodosum;Fucus vesiculosus;seaweed extracts;PTEN/PI3K/AKT;restenosis,;macrophage;vascular smooth muscle cells;gut microbiota.
Date:	2023-07-13
Issue Date:	2023-09-22 13:51:44 (UTC+8)
Abstract:	Restenosis, a common complication following angioplasty. It has previously been shown that the formation of restenosis is characterized by increased oxidative stress and inflammation which intend leads to an uncontrollable migration and proliferation of vascular smooth muscle cells (VSMCs). The nutraceutical used in this study was InSea2, made up of crude extracts of the seaweeds Ascophyllum nodosum and Fucus vesiculosus. Seaweeds have surfaced as an emerging interest in the biomedical area, mainly due to their contents of bioactive substances which show great potential as anti-inflammatory, anti-microbial, anti-viral and anti-tumour drugs and have also been proven to modulate the gut microbiota. Hence, the aim of this study was to investigate the potential of a seaweed extract, InSea2, in inhibiting neo-intima formation in a rat model of restenosis and also to determine the underlying mechanisms involved in this protective effect. To determine the anti-restenosis effects of this seaweed extract (herein referred to as SE), an in vivo model of balloon angioplasty was performed on six-weeks male Sprague-dawley rats. They were fed orally with SE for 4 weeks prior to vascular injury and sacrificed 2 weeks after injury. histologic staining was done to view intimal thickening. To determine SE’s effect on the increased proliferation, migration and dedifferentiation of VSMCs, platelet derived growth factor-BB (PDGF-BB), a known mitogen, and conditioned medium (CM) from lipopolysaccharide (LPS) -activated macrophages, were used to stimulate these adverse effects. To determine the regulatory effects of SE on inflammation, LPS-stimulated macrophage cells were used. 16s-RNA sequencing was performed on the faecal contents of rats to determine the gut microbiota composition. SE significantly inhibited the progression of intimal hyperplasia in vivo and could attenuate the increased proliferation and migration induced by PDGF-BB and CM. Also, SE attenuated inflammation in macrophages. SE significantly inhibited the production of pro-inflammatory cytokines and chemokines and could mitigate the translocation of NFKB into the nucleus. In addition, SE protected against macrophage-associated and PDGF-BB VSMCs proliferation (partly by arresting the cell cycle progression), migration and dedifferentiation by inhibiting the activation of PI3K, thereby preventing the phosphorylation of AKT and could also increase PTEN’s expression in both the cells and arteries. Hence, this seaweed extract may act as a promising nutraceutical for the management of intimal hyperplasia.
Description:	博士指導教授:WU, CHIEH-HSI 委員:WU, CHIEH-HIS 委員:WU, TZU-HUA 委員:LIN, HENG 委員:WENG, JING-RU 委員:HSU, YUAN-MAN
Data Type:	thesis
Appears in Collections:	[Ph. D. Program for the Clinical Drug Discovery from Botanical Herbs] Dissertations/Theses

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