Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk Factors
ABSTRACT Background and Purpose Cerebral amyloid angiopathy (CAA) is recognized as a major contributor to progressive cognitive decline and cerebral hemorrhages in the elderly population. Currently, there is a global shortage of safe and effective treatments for this condition. Bisdemethoxycurcumin...
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Wiley
2025-01-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.70245 |
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| author | Shudong Lin Guanghua Zhu Juan Xie Xuanwei Wen Limin Deng Sijing Li Guozhi Liu Feiyan Wang Shuangxi Chen Zijian Xiao |
| author_facet | Shudong Lin Guanghua Zhu Juan Xie Xuanwei Wen Limin Deng Sijing Li Guozhi Liu Feiyan Wang Shuangxi Chen Zijian Xiao |
| author_sort | Shudong Lin |
| collection | DOAJ |
| description | ABSTRACT Background and Purpose Cerebral amyloid angiopathy (CAA) is recognized as a major contributor to progressive cognitive decline and cerebral hemorrhages in the elderly population. Currently, there is a global shortage of safe and effective treatments for this condition. Bisdemethoxycurcumin (BDMC) has been demonstrated to exhibit pharmacological effects with anti‐Aβ toxicity properties. Thus, the present study mainly focused on the potential therapeutic effects of BDMC on CAA. Method The 30 male C57BL/6 mice were subjected to chronic treatment with five vascular risk factors (lipopolysaccharide, social stress, streptozotocin, high‐cholesterol diet, and copper‐containing drinking water) for 35 weeks to establish a CAA mouse model. Of these, 15 CAA mice received oral administration of BDMC (50 mg/kg) for two consecutive weeks as an intervention, while the remaining 15 CAA mice received an equal volume of physiological saline by gavage. The study observed the levels of Aβ40 and proinflammatory factors in brain tissue and plasma, Aβ deposition in cerebral blood vessels, microbleeds in brain tissue, expression of proteins related to the cGAS/STING signaling pathway in brain tissue, as well as the contents of p‐RIPK‐1, p‐RIPK‐3, p‐MLKL, neuronal morphology, and learning and memory abilities in mice. Result The therapeutic administration of BDMC demonstrates a pronounced efficacy in alleviating Aβ burden and cerebral microbleeding in CAA mice, concurrently enhancing learning and memory capabilities. Interestingly, BDMC may inhibits neuroinflammatory responses by reducing the expression of cGAS/STING signaling pathway proteins and suppresses necroptosis. Conclusion Our research findings demonstrate that BDMC exerts therapeutic effects in a mouse model of CAA established through chronic treatment involving five vascular risk factors. |
| format | Article |
| id | doaj-art-d5c921fefc734fdea362d37e9028e7fd |
| institution | Kabale University |
| issn | 2162-3279 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj-art-d5c921fefc734fdea362d37e9028e7fd2025-01-29T13:36:40ZengWileyBrain and Behavior2162-32792025-01-01151n/an/a10.1002/brb3.70245Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk FactorsShudong Lin0Guanghua Zhu1Juan Xie2Xuanwei Wen3Limin Deng4Sijing Li5Guozhi Liu6Feiyan Wang7Shuangxi Chen8Zijian Xiao9Department of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaDepartment of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaDepartment of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaDepartment of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaDepartment of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaDepartment of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaDepartment of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaDepartment of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaDepartment of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaDepartment of Neurology, The First Affiliated Hospital, Multi‐Omics Research Center for Brain Disorders, Hengyang Medical School University Of South China Hengyang Hunan ChinaABSTRACT Background and Purpose Cerebral amyloid angiopathy (CAA) is recognized as a major contributor to progressive cognitive decline and cerebral hemorrhages in the elderly population. Currently, there is a global shortage of safe and effective treatments for this condition. Bisdemethoxycurcumin (BDMC) has been demonstrated to exhibit pharmacological effects with anti‐Aβ toxicity properties. Thus, the present study mainly focused on the potential therapeutic effects of BDMC on CAA. Method The 30 male C57BL/6 mice were subjected to chronic treatment with five vascular risk factors (lipopolysaccharide, social stress, streptozotocin, high‐cholesterol diet, and copper‐containing drinking water) for 35 weeks to establish a CAA mouse model. Of these, 15 CAA mice received oral administration of BDMC (50 mg/kg) for two consecutive weeks as an intervention, while the remaining 15 CAA mice received an equal volume of physiological saline by gavage. The study observed the levels of Aβ40 and proinflammatory factors in brain tissue and plasma, Aβ deposition in cerebral blood vessels, microbleeds in brain tissue, expression of proteins related to the cGAS/STING signaling pathway in brain tissue, as well as the contents of p‐RIPK‐1, p‐RIPK‐3, p‐MLKL, neuronal morphology, and learning and memory abilities in mice. Result The therapeutic administration of BDMC demonstrates a pronounced efficacy in alleviating Aβ burden and cerebral microbleeding in CAA mice, concurrently enhancing learning and memory capabilities. Interestingly, BDMC may inhibits neuroinflammatory responses by reducing the expression of cGAS/STING signaling pathway proteins and suppresses necroptosis. Conclusion Our research findings demonstrate that BDMC exerts therapeutic effects in a mouse model of CAA established through chronic treatment involving five vascular risk factors.https://doi.org/10.1002/brb3.70245cerebral amyloid angiopathy (CAA)curcuminlearning and memorynecroptosisneuroinflammation |
| spellingShingle | Shudong Lin Guanghua Zhu Juan Xie Xuanwei Wen Limin Deng Sijing Li Guozhi Liu Feiyan Wang Shuangxi Chen Zijian Xiao Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk Factors Brain and Behavior cerebral amyloid angiopathy (CAA) curcumin learning and memory necroptosis neuroinflammation |
| title | Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk Factors |
| title_full | Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk Factors |
| title_fullStr | Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk Factors |
| title_full_unstemmed | Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk Factors |
| title_short | Study on the Therapeutic Effects of Bisdemethoxycurcumin on a Cerebral Amyloid Angiopathy Mouse Model Established via Chronic Treatment With Five Vascular Risk Factors |
| title_sort | study on the therapeutic effects of bisdemethoxycurcumin on a cerebral amyloid angiopathy mouse model established via chronic treatment with five vascular risk factors |
| topic | cerebral amyloid angiopathy (CAA) curcumin learning and memory necroptosis neuroinflammation |
| url | https://doi.org/10.1002/brb3.70245 |
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