A 4.7-kDa polysaccharide from Panax ginseng suppresses Aβ pathology via mitophagy activation in cross-species Alzheimer’s disease models
Alzheimer's disease (AD) is a neurological condition that progresses with age. Amyloid-β (Aβ) aggregation has been suggested to be a key pathogenic process in Alzheimer's disease. Ginseng polysaccharides (GP), the main biologically active components isolated from Panax ginseng C. A. Meyer...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223012404 |
| _version_ | 1797660562625134592 |
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| author | Shuai Zhang Fangbing Liu Jinmeng Li Chenxu Jing Jing Lu Xuenan Chen Dandan Wang Donghui Cao Daqing Zhao Liwei Sun |
| author_facet | Shuai Zhang Fangbing Liu Jinmeng Li Chenxu Jing Jing Lu Xuenan Chen Dandan Wang Donghui Cao Daqing Zhao Liwei Sun |
| author_sort | Shuai Zhang |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is a neurological condition that progresses with age. Amyloid-β (Aβ) aggregation has been suggested to be a key pathogenic process in Alzheimer's disease. Ginseng polysaccharides (GP), the main biologically active components isolated from Panax ginseng C. A. Meyer (ginseng), may act as neuroprotective agents with potential benefits for AD patients. However, GP effects on Aβ pathology and AD symptoms are still unclear. Here, a 4.7-kDa GP termed GP4 was purified and subjected to basic physicochemical characterization. The biological effects of GP4 to prevent Aβ aggregation were then assessed with cross-species AD models, including Aftin-5-treated SH-SY5Y cells and cerebral organoids, and transgenic C. elegans overexpressing the full-length human Aβ42 peptide. These analyses ultimately demonstrated that GP4 was capable of inhibiting Aβ accumulation both in vivo and vitro, and with early intervention of GP4 being sufficient to alleviate Aβ42-associated aging phenotypes and memory loss in C. elegans model of AD. Furthermore, neuroinflammation was significantly down-regulated in human cells and cerebral organoids. From a mechanistic perspective, the ability of GP4 to inhibit Aβ aggregation was found to be related to its ability to promote neuronal mitophagic activity. This finding offers a robust theoretical foundation for the further development of GP4 as a candidate drugs with the potential to treat AD. |
| first_indexed | 2024-03-11T18:31:41Z |
| format | Article |
| id | doaj.art-3373d1ebec3d45a58a04da6b98440708 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-11T18:31:41Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-3373d1ebec3d45a58a04da6b984407082023-10-13T11:02:38ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-11-01167115442A 4.7-kDa polysaccharide from Panax ginseng suppresses Aβ pathology via mitophagy activation in cross-species Alzheimer’s disease modelsShuai Zhang0Fangbing Liu1Jinmeng Li2Chenxu Jing3Jing Lu4Xuenan Chen5Dandan Wang6Donghui Cao7Daqing Zhao8Liwei Sun9Northeast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaNortheast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130117, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130117, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130117, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130117, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130117, ChinaDivision of Clinical Research, First Hospital of Jilin University, Changchun 130117, ChinaNortheast Asian Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, ChinaResearch Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130117, China; Correspondence to: Research Center of Traditional Chinese Medicine, the Affiliated Hospital to Changchun University of Chinese Medicine, 1478 Gongnong Road, Changchun 130117, China.Alzheimer's disease (AD) is a neurological condition that progresses with age. Amyloid-β (Aβ) aggregation has been suggested to be a key pathogenic process in Alzheimer's disease. Ginseng polysaccharides (GP), the main biologically active components isolated from Panax ginseng C. A. Meyer (ginseng), may act as neuroprotective agents with potential benefits for AD patients. However, GP effects on Aβ pathology and AD symptoms are still unclear. Here, a 4.7-kDa GP termed GP4 was purified and subjected to basic physicochemical characterization. The biological effects of GP4 to prevent Aβ aggregation were then assessed with cross-species AD models, including Aftin-5-treated SH-SY5Y cells and cerebral organoids, and transgenic C. elegans overexpressing the full-length human Aβ42 peptide. These analyses ultimately demonstrated that GP4 was capable of inhibiting Aβ accumulation both in vivo and vitro, and with early intervention of GP4 being sufficient to alleviate Aβ42-associated aging phenotypes and memory loss in C. elegans model of AD. Furthermore, neuroinflammation was significantly down-regulated in human cells and cerebral organoids. From a mechanistic perspective, the ability of GP4 to inhibit Aβ aggregation was found to be related to its ability to promote neuronal mitophagic activity. This finding offers a robust theoretical foundation for the further development of GP4 as a candidate drugs with the potential to treat AD.http://www.sciencedirect.com/science/article/pii/S0753332223012404Alzheimer’s diseaseAmyloid-βGP4Caenorhabditis elegansCerebral organoidMitophagy |
| spellingShingle | Shuai Zhang Fangbing Liu Jinmeng Li Chenxu Jing Jing Lu Xuenan Chen Dandan Wang Donghui Cao Daqing Zhao Liwei Sun A 4.7-kDa polysaccharide from Panax ginseng suppresses Aβ pathology via mitophagy activation in cross-species Alzheimer’s disease models Biomedicine & Pharmacotherapy Alzheimer’s disease Amyloid-β GP4 Caenorhabditis elegans Cerebral organoid Mitophagy |
| title | A 4.7-kDa polysaccharide from Panax ginseng suppresses Aβ pathology via mitophagy activation in cross-species Alzheimer’s disease models |
| title_full | A 4.7-kDa polysaccharide from Panax ginseng suppresses Aβ pathology via mitophagy activation in cross-species Alzheimer’s disease models |
| title_fullStr | A 4.7-kDa polysaccharide from Panax ginseng suppresses Aβ pathology via mitophagy activation in cross-species Alzheimer’s disease models |
| title_full_unstemmed | A 4.7-kDa polysaccharide from Panax ginseng suppresses Aβ pathology via mitophagy activation in cross-species Alzheimer’s disease models |
| title_short | A 4.7-kDa polysaccharide from Panax ginseng suppresses Aβ pathology via mitophagy activation in cross-species Alzheimer’s disease models |
| title_sort | 4 7 kda polysaccharide from panax ginseng suppresses aβ pathology via mitophagy activation in cross species alzheimer s disease models |
| topic | Alzheimer’s disease Amyloid-β GP4 Caenorhabditis elegans Cerebral organoid Mitophagy |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223012404 |
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