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ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
Volume 17 - 2025 | doi: 10.3389/fnagi.2025.1521353
This article is part of the Research Topic Role of advanced glycation end products in vascular aging and vascular dementia View all 3 articles
Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation
Provisionally accepted
Meixi Li 1*
Jiaxi Song 1
Xiaoli Niu 1
Feng Mo 1 Xiaohua Xie 1 Xiuqin Li 1
Yu Yin 1
Tianjun Wang 1 Xiujuan Song 2
Jingze Liu 3
Peiyuan Lv 1- 1 Hebei General Hospital, Shijiazhuang, China
- 2 Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
- 3 Hebei Normal University, Shijiazhuang, Hebei Province, China
The potential for therapeutic strategies that promote angiogenesis and suppress neuroinflammation to ameliorate cognitive decline induced by chronic cerebral hypoperfusion (CCH) has led to their recognition as promising therapeutic targets for vascular dementia (VD). The SIRT1-mediated Notch1 signaling pathway is important in regulating angiogenesis and neuroinflammation. Previous studies have demonstrated that baicalein alleviates cognitive decline in rats with CCH rats. Nevertheless, it remains unclear whether baicalein can stimulate angiogenesis in the context of VD and whether this cognitive protective effect is achieved by regulating the SIRT1-mediated Notch1 pathway. The aim of this study was to investigate the impact and the underlying mechanism of baicalein on angiogenesis and neuroinflammation in rats with CCH rats. Adult Sprague-Dawley (SD) rats were administered baicalein or a SIRT1 inhibitor. Cognitive function was assessed by the Morris water maze (MWM) test, and angiogenesis was assessed by immunohistochemical analysis of microvascular density (MVD) and the number of CD31+/5-bromo-2'-deoxyuridine (BrdU)+ cells. Neuroinflammation and apoptosis were assessed by immunohistochemistry for GFAP, Iba-1, NEUN/cleaved caspase-3, and ELISA analysis for TNF-α and IL-1β. Additionally, Western blotting was employed to evaluate the expression of the SIRT1mediated Notch1 pathway. The results demonstrated that baicalein ameliorated memory and learning 设置了格式: 字体颜色: 红色 设置了格式: 字体颜色: 红色deficits in rats following CCH by promoting angiogenesis and suppressing neuroinflammation. However, this protective effect could be reversed by inhibiting SIRT1, indicating that the SIRT1-related pathway plays a crucial role in regulating angiogenesis and neuroinflammation. Moreover, baicalein was observed to up-regulate the expression of SIRT1 and down-regulate the Notch1-related molecules, indicating that baicalein exerts a neuroprotective effect against cognitive decline through the SIRT1-mediated Notch1 pathway, which in turn improves angiogenesis and suppresses neuroinflammation.
Keywords: Vascular dementia (VD), Baicalein, Angiogenesis, Neuroinflammation, SIRT1-mediated Notch1 pathway
Received: 08 Nov 2024; Accepted: 26 Mar 2025.
Copyright: © 2025 Li, Song, Niu, Mo, Xie, Li, Yin, Wang, Song, Liu and Lv. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Meixi Li, Hebei General Hospital, Shijiazhuang, China
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