Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans
Aging is associated with the increased risk of most age-related diseases in humans. Complanatoside A (CA) is a flavonoid compound isolated from the herbal medicine Semen Astragali Complanati. CA was reported to have potential anti-inflammatory and anti-oxidative activities. In this study, we investi...
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Frontiers Media S.A.
2022-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.931886/full |
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| author | Lin Tan Lin Tan Zhuo-Ya Zheng Lv Huang Zhong Jin Su-Lian Li Gui-Sheng Wu Gui-Sheng Wu Gui-Sheng Wu Huai-Rong Luo Huai-Rong Luo Huai-Rong Luo |
| author_facet | Lin Tan Lin Tan Zhuo-Ya Zheng Lv Huang Zhong Jin Su-Lian Li Gui-Sheng Wu Gui-Sheng Wu Gui-Sheng Wu Huai-Rong Luo Huai-Rong Luo Huai-Rong Luo |
| author_sort | Lin Tan |
| collection | DOAJ |
| description | Aging is associated with the increased risk of most age-related diseases in humans. Complanatoside A (CA) is a flavonoid compound isolated from the herbal medicine Semen Astragali Complanati. CA was reported to have potential anti-inflammatory and anti-oxidative activities. In this study, we investigated whether CA could increase the stress resistance capability and life span of Caenorhabditis elegans. Our results showed that CA could extend the longevity of C. elegans in a dosage-dependent manner, while 50 μM of CA has the best effect and increased the life span of C. elegans by about 16.87%. CA also improved the physiological functions in aging worms, such as enhanced locomotor capacity, and reduced the accumulation of the aging pigment. CA could also reduce the accumulation of toxic proteins (α-synuclein and β-amyloid) and delay the onset of neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, in models of C. elegans. Further investigation has revealed that CA requires DAF-16/FOXO, SKN-1, and HSF-1 to extend the life span of C. elegans. CA could increase the antioxidation and detoxification activities regulated by transcription factor SKN-1 and the heat resistance by activating HSF-1 that mediated the expression of the chaperone heat shock proteins. Our results suggest that CA is a potential antiaging agent worth further research for its pharmacological mechanism and development for pharmaceutical applications. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T22:26:43Z |
| publishDate | 2022-08-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-a339bb24b9b44ed6a1a8b7dde2dabcac2022-12-22T03:59:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.931886931886Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegansLin Tan0Lin Tan1Zhuo-Ya Zheng2Lv Huang3Zhong Jin4Su-Lian Li5Gui-Sheng Wu6Gui-Sheng Wu7Gui-Sheng Wu8Huai-Rong Luo9Huai-Rong Luo10Huai-Rong Luo11Key Laboratory for Aging and Regenerative Medicine, Department of Pharmacology School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaDepartment of Pharmacy, Guang’an People’s Hospital, Guang’an, Sichuan, ChinaKey Laboratory for Aging and Regenerative Medicine, Department of Pharmacology School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory for Aging and Regenerative Medicine, Department of Pharmacology School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaLuzhou City Hospital of Traditional Chinese Medicine, Luzhou, Sichuan, ChinaAffiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaKey Laboratory for Aging and Regenerative Medicine, Department of Pharmacology School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaAffiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, Luzhou, Sichuan, ChinaKey Laboratory for Aging and Regenerative Medicine, Department of Pharmacology School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaCentral Nervous System Drug Key Laboratory of Sichuan Province, Luzhou, Sichuan, ChinaKey Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, ChinaAging is associated with the increased risk of most age-related diseases in humans. Complanatoside A (CA) is a flavonoid compound isolated from the herbal medicine Semen Astragali Complanati. CA was reported to have potential anti-inflammatory and anti-oxidative activities. In this study, we investigated whether CA could increase the stress resistance capability and life span of Caenorhabditis elegans. Our results showed that CA could extend the longevity of C. elegans in a dosage-dependent manner, while 50 μM of CA has the best effect and increased the life span of C. elegans by about 16.87%. CA also improved the physiological functions in aging worms, such as enhanced locomotor capacity, and reduced the accumulation of the aging pigment. CA could also reduce the accumulation of toxic proteins (α-synuclein and β-amyloid) and delay the onset of neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease, in models of C. elegans. Further investigation has revealed that CA requires DAF-16/FOXO, SKN-1, and HSF-1 to extend the life span of C. elegans. CA could increase the antioxidation and detoxification activities regulated by transcription factor SKN-1 and the heat resistance by activating HSF-1 that mediated the expression of the chaperone heat shock proteins. Our results suggest that CA is a potential antiaging agent worth further research for its pharmacological mechanism and development for pharmaceutical applications.https://www.frontiersin.org/articles/10.3389/fphar.2022.931886/fullCaenorhabditis elegansagingcomplanatoside ADAF-16/FOXOneurodegenerative diseasesoxidative stress |
| spellingShingle | Lin Tan Lin Tan Zhuo-Ya Zheng Lv Huang Zhong Jin Su-Lian Li Gui-Sheng Wu Gui-Sheng Wu Gui-Sheng Wu Huai-Rong Luo Huai-Rong Luo Huai-Rong Luo Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans Frontiers in Pharmacology Caenorhabditis elegans aging complanatoside A DAF-16/FOXO neurodegenerative diseases oxidative stress |
| title | Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans |
| title_full | Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans |
| title_fullStr | Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans |
| title_full_unstemmed | Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans |
| title_short | Flavonol glycoside complanatoside A requires FOXO/DAF-16, NRF2/SKN-1, and HSF-1 to improve stress resistances and extend the life span of Caenorhabditis elegans |
| title_sort | flavonol glycoside complanatoside a requires foxo daf 16 nrf2 skn 1 and hsf 1 to improve stress resistances and extend the life span of caenorhabditis elegans |
| topic | Caenorhabditis elegans aging complanatoside A DAF-16/FOXO neurodegenerative diseases oxidative stress |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.931886/full |
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