Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation
IntroductionThe 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 N...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Aging Neuroscience |
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| author | Meixi Li Meixi Li Meixi Li Meixi Li Meixi Li Jiaxi Song Jiaxi Song Xiaoli Niu Xiaoli Niu Feng Mo Xiaohua Xie Xiaohua Xie Xiuqin Li Yu Yin Tianjun Wang Tianjun Wang Xiujuan Song Jingze Liu Jingze Liu Peiyuan Lv Peiyuan Lv Peiyuan Lv |
| author_facet | Meixi Li Meixi Li Meixi Li Meixi Li Meixi Li Jiaxi Song Jiaxi Song Xiaoli Niu Xiaoli Niu Feng Mo Xiaohua Xie Xiaohua Xie Xiuqin Li Yu Yin Tianjun Wang Tianjun Wang Xiujuan Song Jingze Liu Jingze Liu Peiyuan Lv Peiyuan Lv Peiyuan Lv |
| author_sort | Meixi Li |
| collection | DOAJ |
| description | IntroductionThe 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. 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.MethodsAdult 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 SIRT1-mediated Notch1 pathway.ResultsThe results demonstrated that baicalein ameliorated memory and learning deficits in rats following CCH by promoting angiogenesis and suppressing neuroinflammation. However, this protective effect could be reversed by inhibiting SIRT1. Baicalein was observed to up-regulate the expression of SIRT1 and down-regulate the Notch1-related molecules.DiscussionThe SIRT1-related pathway plays a crucial role in regulating angiogenesis and neuroinflammation. Moreover, baicalein exerts a neuroprotective effect against cognitive decline through the SIRT1-mediated Notch1 pathway, which in turn improves angiogenesis and suppresses neuroinflammation. |
| format | Article |
| id | doaj-art-6e76ff465d0c47a89c14d3c19ec99cba |
| institution | DOAJ |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-6e76ff465d0c47a89c14d3c19ec99cba2025-08-20T03:06:30ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-04-011710.3389/fnagi.2025.15213531521353Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammationMeixi Li0Meixi Li1Meixi Li2Meixi Li3Meixi Li4Jiaxi Song5Jiaxi Song6Xiaoli Niu7Xiaoli Niu8Feng Mo9Xiaohua Xie10Xiaohua Xie11Xiuqin Li12Yu Yin13Tianjun Wang14Tianjun Wang15Xiujuan Song16Jingze Liu17Jingze Liu18Peiyuan Lv19Peiyuan Lv20Peiyuan Lv21Postdoctoral Innovation Practice Base of Hebei General Hospital, Shijiazhuang, Hebei, ChinaPostdoctoral Research Station of Biology, Hebei Normal University, Shijiazhuang, Hebei, ChinaDepartment of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Cerebral Networks and Cognitive Disorders, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Rehabilitation, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Cerebral Networks and Cognitive Disorders, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Cerebral Networks and Cognitive Disorders, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Neurosurgery, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Cerebral Networks and Cognitive Disorders, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Geriatrics, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Rehabilitation, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Cerebral Networks and Cognitive Disorders, Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaPostdoctoral Research Station of Biology, Hebei Normal University, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology, College of Life Sciences, Hebei Normal University, Shijiazhuang, Hebei, ChinaPostdoctoral Innovation Practice Base of Hebei General Hospital, Shijiazhuang, Hebei, ChinaDepartment of Neurology, Hebei General Hospital, Shijiazhuang, Hebei, ChinaHebei Key Laboratory of Cerebral Networks and Cognitive Disorders, Hebei General Hospital, Shijiazhuang, Hebei, ChinaIntroductionThe 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. 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.MethodsAdult 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 SIRT1-mediated Notch1 pathway.ResultsThe results demonstrated that baicalein ameliorated memory and learning deficits in rats following CCH by promoting angiogenesis and suppressing neuroinflammation. However, this protective effect could be reversed by inhibiting SIRT1. Baicalein was observed to up-regulate the expression of SIRT1 and down-regulate the Notch1-related molecules.DiscussionThe SIRT1-related pathway plays a crucial role in regulating angiogenesis and neuroinflammation. Moreover, baicalein exerts a neuroprotective effect against cognitive decline through the SIRT1-mediated Notch1 pathway, which in turn improves angiogenesis and suppresses neuroinflammation.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1521353/fullvascular dementia (VD)baicaleinangiogenesisneuroinflammationSIRT1-mediated Notch1 pathway |
| spellingShingle | Meixi Li Meixi Li Meixi Li Meixi Li Meixi Li Jiaxi Song Jiaxi Song Xiaoli Niu Xiaoli Niu Feng Mo Xiaohua Xie Xiaohua Xie Xiuqin Li Yu Yin Tianjun Wang Tianjun Wang Xiujuan Song Jingze Liu Jingze Liu Peiyuan Lv Peiyuan Lv Peiyuan Lv Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation Frontiers in Aging Neuroscience vascular dementia (VD) baicalein angiogenesis neuroinflammation SIRT1-mediated Notch1 pathway |
| title | Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation |
| title_full | Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation |
| title_fullStr | Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation |
| title_full_unstemmed | Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation |
| title_short | Baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the SIRT1-mediated Notch1 pathway to improve angiogenesis and suppress neuroinflammation |
| title_sort | baicalein ameliorates cognitive decline induced by chronic cerebral hypoperfusion through the sirt1 mediated notch1 pathway to improve angiogenesis and suppress neuroinflammation |
| topic | vascular dementia (VD) baicalein angiogenesis neuroinflammation SIRT1-mediated Notch1 pathway |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1521353/full |
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