Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathway
BackgroundMitochondrial oxidative damage in pancreatic β-cells is a key contributor to diabetes pathogenesis, particularly under hyperglycemic conditions. Polygonatum sibiricum polysaccharides (PSP) have demonstrated potential anti-diabetic effects; however, their precise mechanism, particularly thr...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Nutrition |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnut.2025.1601490/full |
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| author | Fan Lin Wenjing Yu Wenjing Yu Ping Li Ping Li Shuyao Tang Yitong Ouyang Liya Huang Di Wu Shaowu Cheng Shaowu Cheng Zhenyan Song Zhenyan Song |
| author_facet | Fan Lin Wenjing Yu Wenjing Yu Ping Li Ping Li Shuyao Tang Yitong Ouyang Liya Huang Di Wu Shaowu Cheng Shaowu Cheng Zhenyan Song Zhenyan Song |
| author_sort | Fan Lin |
| collection | DOAJ |
| description | BackgroundMitochondrial oxidative damage in pancreatic β-cells is a key contributor to diabetes pathogenesis, particularly under hyperglycemic conditions. Polygonatum sibiricum polysaccharides (PSP) have demonstrated potential anti-diabetic effects; however, their precise mechanism, particularly through the AMPK-SIRT1 pathway, remains unclear.MethodsA diabetic zebrafish model was established by exposure to 2% glucose for 28 days. Zebrafish were divided into control, model, low-dose PSP (50 μg/mL), medium-dose PSP (100 μg/mL), high-dose PSP (200 μg/mL), and metformin groups. Behavioral, biochemical, and molecular analyses were performed to assess β-cell function, mitochondrial oxidative damage, and inflammation. Network pharmacology analysis was used to predict PSP targets, and molecular docking validated key protein interactions. Immunofluorescence and Western blotting (WB) were conducted to examine apoptosis-related protein expression.ResultsPolygonatum sibiricum polysaccharides significantly improved zebrafish swimming behavior, reduced blood glucose and fructosamine levels, and enhanced ATP production (p < 0.01). Antioxidant enzyme activities (SOD, CAT) increased, while oxidative stress markers (MDA) and inflammatory cytokines (IL-1β, IL-6, TNF-α) decreased (p < 0.01). PSP treatment downregulated Cycs expression, alleviating mitochondrial damage. Moreover, PSP upregulated AMPK and SIRT1 expression (p < 0.01), along with downstream regulators PGC-1α and Nrf1/2 (p < 0.01), confirming AMPK-SIRT1 pathway activation. Network pharmacology identified 389 shared targets between PSP and diabetes-related pathways, implicating key mechanisms of inflammation, insulin resistance, and mitochondrial dysfunction. Molecular docking demonstrated strong PSP binding affinities to AMPK and SIRT1. Immunofluorescence and WB analyses showed reduced cleaved caspase-3 levels and apoptosis in pancreatic β-cells following PSP treatment (p < 0.01).ConclusionPolygonatum sibiricum polysaccharides protects pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative stress and apoptosis via AMPK-SIRT1 pathway activation. Network pharmacology and molecular docking further highlight PSP’s potential as a multi-target therapeutic agent for diabetes. |
| format | Article |
| id | doaj-art-edadbc221a524d8b808ded9b3d866b87 |
| institution | Kabale University |
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| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-edadbc221a524d8b808ded9b3d866b872025-08-20T03:47:41ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2025-05-011210.3389/fnut.2025.16014901601490Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathwayFan Lin0Wenjing Yu1Wenjing Yu2Ping Li3Ping Li4Shuyao Tang5Yitong Ouyang6Liya Huang7Di Wu8Shaowu Cheng9Shaowu Cheng10Zhenyan Song11Zhenyan Song12School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, ChinaSchool of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, ChinaKey Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, Hunan University of Chinese Medicine, Changsha, ChinaBackgroundMitochondrial oxidative damage in pancreatic β-cells is a key contributor to diabetes pathogenesis, particularly under hyperglycemic conditions. Polygonatum sibiricum polysaccharides (PSP) have demonstrated potential anti-diabetic effects; however, their precise mechanism, particularly through the AMPK-SIRT1 pathway, remains unclear.MethodsA diabetic zebrafish model was established by exposure to 2% glucose for 28 days. Zebrafish were divided into control, model, low-dose PSP (50 μg/mL), medium-dose PSP (100 μg/mL), high-dose PSP (200 μg/mL), and metformin groups. Behavioral, biochemical, and molecular analyses were performed to assess β-cell function, mitochondrial oxidative damage, and inflammation. Network pharmacology analysis was used to predict PSP targets, and molecular docking validated key protein interactions. Immunofluorescence and Western blotting (WB) were conducted to examine apoptosis-related protein expression.ResultsPolygonatum sibiricum polysaccharides significantly improved zebrafish swimming behavior, reduced blood glucose and fructosamine levels, and enhanced ATP production (p < 0.01). Antioxidant enzyme activities (SOD, CAT) increased, while oxidative stress markers (MDA) and inflammatory cytokines (IL-1β, IL-6, TNF-α) decreased (p < 0.01). PSP treatment downregulated Cycs expression, alleviating mitochondrial damage. Moreover, PSP upregulated AMPK and SIRT1 expression (p < 0.01), along with downstream regulators PGC-1α and Nrf1/2 (p < 0.01), confirming AMPK-SIRT1 pathway activation. Network pharmacology identified 389 shared targets between PSP and diabetes-related pathways, implicating key mechanisms of inflammation, insulin resistance, and mitochondrial dysfunction. Molecular docking demonstrated strong PSP binding affinities to AMPK and SIRT1. Immunofluorescence and WB analyses showed reduced cleaved caspase-3 levels and apoptosis in pancreatic β-cells following PSP treatment (p < 0.01).ConclusionPolygonatum sibiricum polysaccharides protects pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative stress and apoptosis via AMPK-SIRT1 pathway activation. Network pharmacology and molecular docking further highlight PSP’s potential as a multi-target therapeutic agent for diabetes.https://www.frontiersin.org/articles/10.3389/fnut.2025.1601490/fullPolygonatum sibiricum polysaccharidesmitochondrial oxidative damagepancreatic β-cellsAMPK-SIRT1 pathwayzebrafishnetwork pharmacology |
| spellingShingle | Fan Lin Wenjing Yu Wenjing Yu Ping Li Ping Li Shuyao Tang Yitong Ouyang Liya Huang Di Wu Shaowu Cheng Shaowu Cheng Zhenyan Song Zhenyan Song Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathway Frontiers in Nutrition Polygonatum sibiricum polysaccharides mitochondrial oxidative damage pancreatic β-cells AMPK-SIRT1 pathway zebrafish network pharmacology |
| title | Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathway |
| title_full | Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathway |
| title_fullStr | Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathway |
| title_full_unstemmed | Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathway |
| title_short | Polygonatum sibiricum polysaccharides enhance pancreatic β-cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the AMPK-SIRT1 pathway |
| title_sort | polygonatum sibiricum polysaccharides enhance pancreatic β cell function in diabetic zebrafish by mitigating mitochondrial oxidative damage via the ampk sirt1 pathway |
| topic | Polygonatum sibiricum polysaccharides mitochondrial oxidative damage pancreatic β-cells AMPK-SIRT1 pathway zebrafish network pharmacology |
| url | https://www.frontiersin.org/articles/10.3389/fnut.2025.1601490/full |
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