Bushen-Yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via AMPK/Sirt1 signaling pathway in D-gal-induced aging rats
Abstract Background As a major risk factor for neurodegenerative diseases, aging has become a heavy health care burden worldwide. Age-related decline in mitochondrial function and oxidative stress is strongly associated with neurodegeneration. The previous study demonstrated that Bushen-Yizhi formul...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | Chinese Medicine |
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| Online Access: | https://doi.org/10.1186/s13020-023-00755-3 |
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| author | Yanfang Liao Yiyi Lai Huilin Xu Li Gao Xiaomei Fu Xue Wang Qi Wang Jiangang Shen Jiansong Fang Shuhuan Fang |
| author_facet | Yanfang Liao Yiyi Lai Huilin Xu Li Gao Xiaomei Fu Xue Wang Qi Wang Jiangang Shen Jiansong Fang Shuhuan Fang |
| author_sort | Yanfang Liao |
| collection | DOAJ |
| description | Abstract Background As a major risk factor for neurodegenerative diseases, aging has become a heavy health care burden worldwide. Age-related decline in mitochondrial function and oxidative stress is strongly associated with neurodegeneration. The previous study demonstrated that Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine formula, is effective in reducing neurodegeneration. Methods This study is the first to investigate the effect of BSYZ on D-gal-induced learning memory in rats. Secondly, the potential metabolic mechanism of BSYZ was explored by 1H-NMR metabolomics analysis. Then based on the comparison of differential metabolites implied that BSYZ ameliorated mitochondrial dysfunction through choline metabolic pathway in D-gal-treated rats. Finally, pharmacological validation was conducted to explore the effects of BSYZ on D-gal-induced oxidative stress, neuroinflammation, and neuronal apoptosis. Results Our data showed that BSYZ increased aspartate and betaine levels, while decreasing choline levels. Furthermore, BSYZ also increased the proteins level of CHDH and BHMT to regulate choline metabolic pathway. Meanwhile, BSYZ alleviated mitochondrial damage and oxidative stress, including enhanced ATP production and the ratio of NAD+/NADH, reduced the level of MDA, enhanced GSH and SOD activity, upregulated the expressions of p-AMPK, SIRT1 proteins. In addition, BSYZ downregulated the levels of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, as well as suppressed Bcl-2 proteins family dependent apoptosis. Conclusion BSYZ treatment effectively rescues neurobehavioral impairment by improving mitochondrial dysfunction, oxidative stress, neuroinflammation and neuroapoptosis via AMPK/SIRT1 pathway in D-gal-induced aging. |
| first_indexed | 2024-04-09T12:47:31Z |
| format | Article |
| id | doaj.art-a5571c4fca9c4f83bb3fff949163f164 |
| institution | Directory Open Access Journal |
| issn | 1749-8546 |
| language | English |
| last_indexed | 2024-04-09T12:47:31Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Chinese Medicine |
| spelling | doaj.art-a5571c4fca9c4f83bb3fff949163f1642023-05-14T11:27:41ZengBMCChinese Medicine1749-85462023-05-0118111810.1186/s13020-023-00755-3Bushen-Yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via AMPK/Sirt1 signaling pathway in D-gal-induced aging ratsYanfang Liao0Yiyi Lai1Huilin Xu2Li Gao3Xiaomei Fu4Xue Wang5Qi Wang6Jiangang Shen7Jiansong Fang8Shuhuan Fang9Science and Technology Innovation Center, Guangzhou University of Chinese MedicineScience and Technology Innovation Center, Guangzhou University of Chinese MedicineScience and Technology Innovation Center, Guangzhou University of Chinese MedicineModern Research Center for Traditional Chinese Medicine, Shanxi UniversityScience and Technology Innovation Center, Guangzhou University of Chinese MedicineScience and Technology Innovation Center, Guangzhou University of Chinese MedicineScience and Technology Innovation Center, Guangzhou University of Chinese MedicineSchool of Chinese Medicine, the University of Hong KongScience and Technology Innovation Center, Guangzhou University of Chinese MedicineScience and Technology Innovation Center, Guangzhou University of Chinese MedicineAbstract Background As a major risk factor for neurodegenerative diseases, aging has become a heavy health care burden worldwide. Age-related decline in mitochondrial function and oxidative stress is strongly associated with neurodegeneration. The previous study demonstrated that Bushen-Yizhi formula (BSYZ), a traditional Chinese medicine formula, is effective in reducing neurodegeneration. Methods This study is the first to investigate the effect of BSYZ on D-gal-induced learning memory in rats. Secondly, the potential metabolic mechanism of BSYZ was explored by 1H-NMR metabolomics analysis. Then based on the comparison of differential metabolites implied that BSYZ ameliorated mitochondrial dysfunction through choline metabolic pathway in D-gal-treated rats. Finally, pharmacological validation was conducted to explore the effects of BSYZ on D-gal-induced oxidative stress, neuroinflammation, and neuronal apoptosis. Results Our data showed that BSYZ increased aspartate and betaine levels, while decreasing choline levels. Furthermore, BSYZ also increased the proteins level of CHDH and BHMT to regulate choline metabolic pathway. Meanwhile, BSYZ alleviated mitochondrial damage and oxidative stress, including enhanced ATP production and the ratio of NAD+/NADH, reduced the level of MDA, enhanced GSH and SOD activity, upregulated the expressions of p-AMPK, SIRT1 proteins. In addition, BSYZ downregulated the levels of inflammatory cytokines, such as TNF-α, IL-1β and IL-6, as well as suppressed Bcl-2 proteins family dependent apoptosis. Conclusion BSYZ treatment effectively rescues neurobehavioral impairment by improving mitochondrial dysfunction, oxidative stress, neuroinflammation and neuroapoptosis via AMPK/SIRT1 pathway in D-gal-induced aging.https://doi.org/10.1186/s13020-023-00755-3Bushen-Yizhi formulaD-galactose-induced-aging ratsMetabolomicsMitochondrial dysfunctionOxidative stressInflammation |
| spellingShingle | Yanfang Liao Yiyi Lai Huilin Xu Li Gao Xiaomei Fu Xue Wang Qi Wang Jiangang Shen Jiansong Fang Shuhuan Fang Bushen-Yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via AMPK/Sirt1 signaling pathway in D-gal-induced aging rats Chinese Medicine Bushen-Yizhi formula D-galactose-induced-aging rats Metabolomics Mitochondrial dysfunction Oxidative stress Inflammation |
| title | Bushen-Yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via AMPK/Sirt1 signaling pathway in D-gal-induced aging rats |
| title_full | Bushen-Yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via AMPK/Sirt1 signaling pathway in D-gal-induced aging rats |
| title_fullStr | Bushen-Yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via AMPK/Sirt1 signaling pathway in D-gal-induced aging rats |
| title_full_unstemmed | Bushen-Yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via AMPK/Sirt1 signaling pathway in D-gal-induced aging rats |
| title_short | Bushen-Yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via AMPK/Sirt1 signaling pathway in D-gal-induced aging rats |
| title_sort | bushen yizhi formula ameliorates mitochondrial dysfunction and oxidative stress via ampk sirt1 signaling pathway in d gal induced aging rats |
| topic | Bushen-Yizhi formula D-galactose-induced-aging rats Metabolomics Mitochondrial dysfunction Oxidative stress Inflammation |
| url | https://doi.org/10.1186/s13020-023-00755-3 |
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