Intranasal administration of Ganoderma lucidum-derived exosome-like nanovesicles ameliorates cognitive impairment by reducing inflammation in a mouse model of Alzheimer’s disease
Background/ObjectivesAlthough Alzheimer’s disease (AD) is the most prevalent dementia in late life, with amyloid beta (Aβ) deposition and neuroinflammation are recognized among its primary pathological features. Currently, there is currently still a lack of effective therapeutic drugs for AD. Ganode...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1572771/full |
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| author | Xue Mi Xue Mi Xinglin Ruan Renyi Lin Shuxin Huang Ping Cai Xiaochun Chen Xiaochun Chen Jiangfeng Liao Xiaoman Dai Xiaoman Dai |
| author_facet | Xue Mi Xue Mi Xinglin Ruan Renyi Lin Shuxin Huang Ping Cai Xiaochun Chen Xiaochun Chen Jiangfeng Liao Xiaoman Dai Xiaoman Dai |
| author_sort | Xue Mi |
| collection | DOAJ |
| description | Background/ObjectivesAlthough Alzheimer’s disease (AD) is the most prevalent dementia in late life, with amyloid beta (Aβ) deposition and neuroinflammation are recognized among its primary pathological features. Currently, there is currently still a lack of effective therapeutic drugs for AD. Ganoderma lucidum (G. lucidum) is abundant in active ingredients that harbor anti-inflammatory properties in both central nervous system and the periphery. We attempted to determine whether G. lucidum contained exosome-like nanovesicles (GLENVs) and whether these GLENVs can alleviate cognitive impairment.MethodsWe extracted GLENVs by the differential ultracentrifugation method and identified the components by liquid chromatography-mass spectrometry (LC-MS). The 5×FAD mice underwent a 3-month intranasal administration of GLENVs and their behavioral and pathological changes were evaluated.ResultsGLENVs were successfully extracted and identified to contain multiple ganoderic acids; intranasal administration allowed GLENVs to penetrate the blood-brain barrier to exert their effects directly. The 3-month GLENVs treatment effectively ameliorated the impairment in the memory and learning of the 5×FAD mice. The GLENVs treatment also reduced Aβ deposition in the cortex and hippocampus of 5×FAD mice, overactivated microglia, reactive astrocytes, and pro-inflammatory factors, and inhibited the Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) signaling pathway. Moreover, GLENVs exerted no adverse effects on liver and kidney function.ConclusionGLENVs may be a promising candidate for AD treatment. |
| format | Article |
| id | doaj-art-141b707eb47e4fe3a4131063d2d49497 |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-141b707eb47e4fe3a4131063d2d494972025-08-20T03:29:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.15727711572771Intranasal administration of Ganoderma lucidum-derived exosome-like nanovesicles ameliorates cognitive impairment by reducing inflammation in a mouse model of Alzheimer’s diseaseXue Mi0Xue Mi1Xinglin Ruan2Renyi Lin3Shuxin Huang4Ping Cai5Xiaochun Chen6Xiaochun Chen7Jiangfeng Liao8Xiaoman Dai9Xiaoman Dai10Public Technology Service Center, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, ChinaDepartment of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, ChinaSchool of Pharmacy, Fujian Medical University, Fuzhou, ChinaSchool of Public Health, Fujian Medical University, Fuzhou, ChinaSchool of Public Health, Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, ChinaDepartment of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of Neurology, First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaFujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, ChinaDepartment of Neurology and Geriatrics, Fujian Institute of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, ChinaBackground/ObjectivesAlthough Alzheimer’s disease (AD) is the most prevalent dementia in late life, with amyloid beta (Aβ) deposition and neuroinflammation are recognized among its primary pathological features. Currently, there is currently still a lack of effective therapeutic drugs for AD. Ganoderma lucidum (G. lucidum) is abundant in active ingredients that harbor anti-inflammatory properties in both central nervous system and the periphery. We attempted to determine whether G. lucidum contained exosome-like nanovesicles (GLENVs) and whether these GLENVs can alleviate cognitive impairment.MethodsWe extracted GLENVs by the differential ultracentrifugation method and identified the components by liquid chromatography-mass spectrometry (LC-MS). The 5×FAD mice underwent a 3-month intranasal administration of GLENVs and their behavioral and pathological changes were evaluated.ResultsGLENVs were successfully extracted and identified to contain multiple ganoderic acids; intranasal administration allowed GLENVs to penetrate the blood-brain barrier to exert their effects directly. The 3-month GLENVs treatment effectively ameliorated the impairment in the memory and learning of the 5×FAD mice. The GLENVs treatment also reduced Aβ deposition in the cortex and hippocampus of 5×FAD mice, overactivated microglia, reactive astrocytes, and pro-inflammatory factors, and inhibited the Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) signaling pathway. Moreover, GLENVs exerted no adverse effects on liver and kidney function.ConclusionGLENVs may be a promising candidate for AD treatment.https://www.frontiersin.org/articles/10.3389/fphar.2025.1572771/fullGanoderma. lucidum (G. lucidum)-derived exosome-like nanovesiclescognitive impairmentinflammatory responseAlzheimer’s diseaseintranasal administration |
| spellingShingle | Xue Mi Xue Mi Xinglin Ruan Renyi Lin Shuxin Huang Ping Cai Xiaochun Chen Xiaochun Chen Jiangfeng Liao Xiaoman Dai Xiaoman Dai Intranasal administration of Ganoderma lucidum-derived exosome-like nanovesicles ameliorates cognitive impairment by reducing inflammation in a mouse model of Alzheimer’s disease Frontiers in Pharmacology Ganoderma. lucidum (G. lucidum)-derived exosome-like nanovesicles cognitive impairment inflammatory response Alzheimer’s disease intranasal administration |
| title | Intranasal administration of Ganoderma lucidum-derived exosome-like nanovesicles ameliorates cognitive impairment by reducing inflammation in a mouse model of Alzheimer’s disease |
| title_full | Intranasal administration of Ganoderma lucidum-derived exosome-like nanovesicles ameliorates cognitive impairment by reducing inflammation in a mouse model of Alzheimer’s disease |
| title_fullStr | Intranasal administration of Ganoderma lucidum-derived exosome-like nanovesicles ameliorates cognitive impairment by reducing inflammation in a mouse model of Alzheimer’s disease |
| title_full_unstemmed | Intranasal administration of Ganoderma lucidum-derived exosome-like nanovesicles ameliorates cognitive impairment by reducing inflammation in a mouse model of Alzheimer’s disease |
| title_short | Intranasal administration of Ganoderma lucidum-derived exosome-like nanovesicles ameliorates cognitive impairment by reducing inflammation in a mouse model of Alzheimer’s disease |
| title_sort | intranasal administration of ganoderma lucidum derived exosome like nanovesicles ameliorates cognitive impairment by reducing inflammation in a mouse model of alzheimer s disease |
| topic | Ganoderma. lucidum (G. lucidum)-derived exosome-like nanovesicles cognitive impairment inflammatory response Alzheimer’s disease intranasal administration |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1572771/full |
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