Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD Model

Introduction: Salidroside (SAL), extracted from Rhodiola rosea, has been widely used in coronary heart disease and myocardial ischemia for decades. Previous studies have demonstrated that SAL could reduce arteriosclerosis, and thus combat ischemic brain damage. However, the in-depth function of the...

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Main Authors: Tu Zhilan, Zhang Zengyu, Jin Pengpeng, Yang Hualan, Li Chao, Xi Yan, Guo Zimin, Hou Shuangxing, Li Weiwei
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Journal of Advanced Research
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Online Access:http://www.sciencedirect.com/science/article/pii/S209012322400081X
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author Tu Zhilan
Zhang Zengyu
Jin Pengpeng
Yang Hualan
Li Chao
Xi Yan
Guo Zimin
Hou Shuangxing
Li Weiwei
author_facet Tu Zhilan
Zhang Zengyu
Jin Pengpeng
Yang Hualan
Li Chao
Xi Yan
Guo Zimin
Hou Shuangxing
Li Weiwei
author_sort Tu Zhilan
collection DOAJ
description Introduction: Salidroside (SAL), extracted from Rhodiola rosea, has been widely used in coronary heart disease and myocardial ischemia for decades. Previous studies have demonstrated that SAL could reduce arteriosclerosis, and thus combat ischemic brain damage. However, the in-depth function of the salidroside in Cerebral Small Vascular Disease (CSVD) has not been discovered, and related molecular mechanism is still unclear. Objectives: The present study aims to explore the effects of salidroside in angiogenesis as well as repair of blood brain barrier (BBB) and its possible mechanisms. Methods: We established a rat model of SHR via 2-vessel gradual occlusion (SHR-2VGO) to mimic the CSVD. Subsequently, the MRI, pathomorphism, as well as Morriss water maze test were conducted to determine CSVD-related indicators. 8 weeks post-surgery, animals were randomly administered SAL, DAPT, ATN161 or saline.The aim was to explore the protective effects of SAL in CSVD as well as its possible mechanism. Results: Here we found that SAL could attenuate cerebral hypoperfusion-induced BBB disruption, promote the pro-angiogenesis through enhancing the cell budding. Further investigations demonstrated that SAL could significantly increase the expression of Notch1, Hes1, Hes5, and ITGB1. In addition, we confirmed that SAL could activate Notch signal path, and then up-regulate ITGB1 to promote pro-angiogenesis and thus protect BBB from disruption. Conclusion: The aforementioned findings demonstrated that SAL could protect BBB integrity through Notch-ITGB1 signaling path in CSVD, which indicated that SAL could be a potential medicine candidate for CSVD treatment.
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publishDate 2025-02-01
publisher Elsevier
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series Journal of Advanced Research
spelling doaj-art-6b636f99a2a048a1b14ef01123ec94942025-01-18T05:04:20ZengElsevierJournal of Advanced Research2090-12322025-02-0168429444Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD ModelTu Zhilan0Zhang Zengyu1Jin Pengpeng2Yang Hualan3Li Chao4Xi Yan5Guo Zimin6Hou Shuangxing7Li Weiwei8Department of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, ChinaDepartment of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China; Shanghai Medical College, Fudan University, Shanghai 200032, ChinaDepartment of Chronic Disease Management, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, ChinaDepartment of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, ChinaVasculocardiology Department, Change County Hospital of Traditional Chinese Medicine, Shandong Province 261300, ChinaDepartment of Radiology, Shanghai TCM-Integrated Hospital, 200082 Shanghai, ChinaDepartment of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, ChinaDepartment of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China; Corresponding authors at: 2800 Gongwei Road, Pudong, Shanghai 201399, China (Hou Shuangxing). Wanyuan road No.399, Minhang district, Shanghai, China (Li Weiwei).Institute of Pediatrics, Children’s Hospital of Fudan University, Fudan University, Shanghai 201102, China; Corresponding authors at: 2800 Gongwei Road, Pudong, Shanghai 201399, China (Hou Shuangxing). Wanyuan road No.399, Minhang district, Shanghai, China (Li Weiwei).Introduction: Salidroside (SAL), extracted from Rhodiola rosea, has been widely used in coronary heart disease and myocardial ischemia for decades. Previous studies have demonstrated that SAL could reduce arteriosclerosis, and thus combat ischemic brain damage. However, the in-depth function of the salidroside in Cerebral Small Vascular Disease (CSVD) has not been discovered, and related molecular mechanism is still unclear. Objectives: The present study aims to explore the effects of salidroside in angiogenesis as well as repair of blood brain barrier (BBB) and its possible mechanisms. Methods: We established a rat model of SHR via 2-vessel gradual occlusion (SHR-2VGO) to mimic the CSVD. Subsequently, the MRI, pathomorphism, as well as Morriss water maze test were conducted to determine CSVD-related indicators. 8 weeks post-surgery, animals were randomly administered SAL, DAPT, ATN161 or saline.The aim was to explore the protective effects of SAL in CSVD as well as its possible mechanism. Results: Here we found that SAL could attenuate cerebral hypoperfusion-induced BBB disruption, promote the pro-angiogenesis through enhancing the cell budding. Further investigations demonstrated that SAL could significantly increase the expression of Notch1, Hes1, Hes5, and ITGB1. In addition, we confirmed that SAL could activate Notch signal path, and then up-regulate ITGB1 to promote pro-angiogenesis and thus protect BBB from disruption. Conclusion: The aforementioned findings demonstrated that SAL could protect BBB integrity through Notch-ITGB1 signaling path in CSVD, which indicated that SAL could be a potential medicine candidate for CSVD treatment.http://www.sciencedirect.com/science/article/pii/S209012322400081XSalidrosideCSVDBlood brain barrierNotch signal pathwayITGB1
spellingShingle Tu Zhilan
Zhang Zengyu
Jin Pengpeng
Yang Hualan
Li Chao
Xi Yan
Guo Zimin
Hou Shuangxing
Li Weiwei
Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD Model
Journal of Advanced Research
Salidroside
CSVD
Blood brain barrier
Notch signal pathway
ITGB1
title Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD Model
title_full Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD Model
title_fullStr Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD Model
title_full_unstemmed Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD Model
title_short Salidroside promotes pro-angiogenesis and repair of blood brain barrier via Notch/ITGB1 signal path in CSVD Model
title_sort salidroside promotes pro angiogenesis and repair of blood brain barrier via notch itgb1 signal path in csvd model
topic Salidroside
CSVD
Blood brain barrier
Notch signal pathway
ITGB1
url http://www.sciencedirect.com/science/article/pii/S209012322400081X
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