Exploring the effect of Polygonatum cyrtonema polysaccharide DPC1 on D-galactose-induced mouse aging model based on AMPK/SIRT1 pathway
Article ID:
4666
Keywords:
Polygonatum cyrtonema polysaccharide; senescence; oxidative; AMPK; SIRT1
Abstract
Objective: The aim of this study was to elucidate the ameliorating mechanism of Polygonatum cyrtonema polysaccharide (DPC1) on D-galactose (D-gal)-induced oxidative stress-induced senescence in mice and to study the mechanism. Design: A model of senescence was established using D-gal (0.12 g/kg at 8 weeks) induced in ICR mice with concomitant gavage administration (0.15, 0.30, or 0.60 g/kg) of DPC1. Measurement of antioxidant indices in mouse tissues and plasma. Observation of pathological changes in mouse brain tissue. The mitochondrial adenosine triphosphate level and mitochondrial membrane potential of the mouse brain tissue samples were then determined. Molecular biotechnologies such as Western blot was used to investigate the AMPK/SIRT1 signaling pathway and related proteins. Results: Oral administration of DPC1 alleviated D-gal-induced oxidative damage in mice, such as the reduction of malondialdehyde (MDA) content and monoamine oxidase (MAO) activity level, and the increase of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) activity levels. At the same time, DPC1 improved the pathological changes of mouse brain tissue. In addition, DPC1 had a restorative effect on both mitochondrial membrane potential (MMP) and ATP content in mouse brain tissues. DPC1-treated group was able to AMP-activated protein kinase/silent information regulator 1 (AMPK/SIRT1) pathway and regulate oxi - dative enzymes by inhibiting the ratio of Acety-Forkhead Box O1/Forkhead Box O1 (Ac-FoxO1/FoxO1), thereby restoring the pro-oxidant/antioxidant balance. It also reduced P53 and P21 expression. Conclusions: Our results suggest that DPC1 inhibits oxidative stress-induced senescence by activating the AMPK/ SIRT1 pathway
Published
2025-08-26
Copyright (c) 2025 丝怡 zhang, teng peng, Yaosong Yang, Guangzhen Cao, Fei Long
This work is licensed under a Creative Commons Attribution 4.0 International License.
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2. Salmon AB, Richardson A, Pérez VI. Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging? Free Radical Biology and Medicine. 2009;48(5):642-55.
3. Denham H. Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009. Biogerontology. 2009;10(6):773-81.
4. Hannah T, Giuseppe C, M RJ. Mitochondria in Ageing and Diseases: Partie Deux. International journal of molecular sciences. 2023;24(12).
5. Wang X, Ma Z, Cheng J, Lv Z. A genetic program theory of aging using an RNA population model. Ageing Research Reviews. 2014;13(1):46-54.
6. Xiao C, Ju D, Kai L, Ying G, Dong W, Ming L, et al. Botany, Traditional Uses, and Pharmacology of Polygonati Rhizoma. Chinese Medicine and Culture. 2021;4(4):251-59.
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11. Chen W, Shen Z, Dong W, Huang G, Yu D, Chen W, et al. Polygonatum sibiricum polysaccharide ameliorates skeletal muscle aging via mitochondria-associated membrane-mediated calcium homeostasis regulation. Phytomedicine. 2024;129:155567.
12. Li D, Meng-Ni N, Jin-Min Z, Xiao-Ming P, Shao-Hui Z, Gao-Feng Z. Polygonatum sibiricum polysaccharide inhibits osteoporosis by promoting osteoblast formation and blocking osteoclastogenesis through Wnt/β-catenin signalling pathway. Scientific reports. 2016;6(1):32261.
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33. Haigis MC, Sinclair DA. Mammalian Sirtuins: Biological Insights and Disease Relevance. Annual Review of Pathology: Mechanisms of Disease. 2010;5(1):253-95.
34. Chen C, Zhou M, Ge Y, Wang X. SIRT1 and aging related signaling pathways. Mechanisms of Ageing and Development. 2020;187:111215.
35. Hui G, Honghan C, Peng X, Ning H, Xiaojuan H, Jian Z, et al. miR-146a impedes the anti-aging effect of AMPK via NAMPT suppression and NAD+/SIRT inactivation. Signal Transduction and Targeted Therapy. 2022;7(1):66-66.
36. S I, M AC, M K, L G. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000;403(6771):795-800.
37. Stavroula K. FoxO1: a molecule for all seasons. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2011;26(5):912-7.
38. Hiroaki D, Mitsutoki H, Hitomi M, Satoko A, Takayuki O, Makoto M, et al. Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Proceedings of the National Academy of Sciences of the United States of America. 2004;101(27):10042-7.
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40. Tamer C, Karolin Y, Pınar A, Tuna O, Irmak KA, Ahmad K, et al. A comprehensive study of myocardial redox homeostasis in naturally and mimetically aged rats. Age (Dordrecht, Netherlands). 2014;36(6):9728.
