Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammation
Alzheimer's disease (AD) is a neurodegenerative disease with amyloid beta (Aβ) deposition and intracellular neurofibrillary tangles (NFTs) as its characteristic pathological changes. Ameliorating oxidative stress and inflammation has become a new trend in the prevention and treatment of AD. Dio...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222006370 |
| _version_ | 1811241317224677376 |
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| author | Linshu Guan Zhang Mao Sen Yang Guanlin Wu Yurong Chen Lianhong Yin Yan Qi Lan Han Lina Xu |
| author_facet | Linshu Guan Zhang Mao Sen Yang Guanlin Wu Yurong Chen Lianhong Yin Yan Qi Lan Han Lina Xu |
| author_sort | Linshu Guan |
| collection | DOAJ |
| description | Alzheimer's disease (AD) is a neurodegenerative disease with amyloid beta (Aβ) deposition and intracellular neurofibrillary tangles (NFTs) as its characteristic pathological changes. Ameliorating oxidative stress and inflammation has become a new trend in the prevention and treatment of AD. Dioscin, a natural steroidal saponin which exists in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in Alzheimer's disease (AD) is still unknown. In the present work, effect of dioscin on AD was evaluated in injured SH-SY5Y cells induced by H2O2 and C57BL/6 mice with AD challenged with AlCl₃ combined with D-galactose. Results showed that dioscin obviously increased cell viability and decreased reactive oxygen species (ROS) level in injured SH-SY5Y cells. In vivo, dioscin obviously improved the spatial learning and memory abilities as well as gait and interlimb coordination disorders of mice with AD. Moreover, dioscin distinctly restored the levels of malondialdehyde (MDA), superoxide dismutase (SOD), amyloid beta 42 (Aβ42), acetylcholine (ACh) and acetylcholinesterase (AChE) of mice, and reversed the histopathological changes of brain tissue. Mechanism studies revealed that dioscin markedly down-regulated the expression levels of RAGE and NOX4. Subsequently, dioscin markedly up-regulated the expression levels of Nrf2 and HO-1 related to oxidative stress, and down-regulated the levels of p-NF-κB(p-p65)/NF-κB(p65), AP-1 and inflammatory factors involved in inflammatory pathway. RAGE siRNAs transfection further clarified that the pharmacological activity of dioscin in AD was achieved by regulating RAGE/NOX4 pathway. In conclusion, dioscin showed excellent anti-AD effect by adjusting RAGE/NOX4-mediated oxidative stress and inflammation, which provided the basis for the further research and development against AD. |
| first_indexed | 2024-04-12T13:33:45Z |
| format | Article |
| id | doaj.art-4e7236867f594213aa89e7d823704139 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-12T13:33:45Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-4e7236867f594213aa89e7d8237041392022-12-22T03:31:05ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-08-01152113248Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammationLinshu Guan0Zhang Mao1Sen Yang2Guanlin Wu3Yurong Chen4Lianhong Yin5Yan Qi6Lan Han7Lina Xu8College of Pharmacy, Dalian Medical University, Dalian 116044, China; The Second Hospital of Dalian Medical University, Dalian 116023, ChinaCollege of Pharmacy, Dalian Medical University, Dalian 116044, ChinaCollege of Pharmacy, Dalian Medical University, Dalian 116044, ChinaCollege of Pharmacy, Dalian Medical University, Dalian 116044, ChinaCollege of Pharmacy, Dalian Medical University, Dalian 116044, ChinaCollege of Pharmacy, Dalian Medical University, Dalian 116044, ChinaCollege of Pharmacy, Dalian Medical University, Dalian 116044, ChinaSchool of pharmacy, Anhui University of Traditional Chinese Medicine, Hefei 230012, China; Correspondence to: School of pharmacy Anhui University of Traditional Chinese Medicine Hefei, China.College of Pharmacy, Dalian Medical University, Dalian 116044, China; Correspondence to: College of Pharmacy Dalian Medical University Dalian, China.Alzheimer's disease (AD) is a neurodegenerative disease with amyloid beta (Aβ) deposition and intracellular neurofibrillary tangles (NFTs) as its characteristic pathological changes. Ameliorating oxidative stress and inflammation has become a new trend in the prevention and treatment of AD. Dioscin, a natural steroidal saponin which exists in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in Alzheimer's disease (AD) is still unknown. In the present work, effect of dioscin on AD was evaluated in injured SH-SY5Y cells induced by H2O2 and C57BL/6 mice with AD challenged with AlCl₃ combined with D-galactose. Results showed that dioscin obviously increased cell viability and decreased reactive oxygen species (ROS) level in injured SH-SY5Y cells. In vivo, dioscin obviously improved the spatial learning and memory abilities as well as gait and interlimb coordination disorders of mice with AD. Moreover, dioscin distinctly restored the levels of malondialdehyde (MDA), superoxide dismutase (SOD), amyloid beta 42 (Aβ42), acetylcholine (ACh) and acetylcholinesterase (AChE) of mice, and reversed the histopathological changes of brain tissue. Mechanism studies revealed that dioscin markedly down-regulated the expression levels of RAGE and NOX4. Subsequently, dioscin markedly up-regulated the expression levels of Nrf2 and HO-1 related to oxidative stress, and down-regulated the levels of p-NF-κB(p-p65)/NF-κB(p65), AP-1 and inflammatory factors involved in inflammatory pathway. RAGE siRNAs transfection further clarified that the pharmacological activity of dioscin in AD was achieved by regulating RAGE/NOX4 pathway. In conclusion, dioscin showed excellent anti-AD effect by adjusting RAGE/NOX4-mediated oxidative stress and inflammation, which provided the basis for the further research and development against AD.http://www.sciencedirect.com/science/article/pii/S0753332222006370DioscinAlzheimer's diseaseOxidative stressInflammationRAGENOX4 |
| spellingShingle | Linshu Guan Zhang Mao Sen Yang Guanlin Wu Yurong Chen Lianhong Yin Yan Qi Lan Han Lina Xu Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammation Biomedicine & Pharmacotherapy Dioscin Alzheimer's disease Oxidative stress Inflammation RAGE NOX4 |
| title | Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammation |
| title_full | Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammation |
| title_fullStr | Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammation |
| title_full_unstemmed | Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammation |
| title_short | Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammation |
| title_sort | dioscin alleviates alzheimer s disease through regulating rage nox4 mediated oxidative stress and inflammation |
| topic | Dioscin Alzheimer's disease Oxidative stress Inflammation RAGE NOX4 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222006370 |
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