Ginsenoside Rh4 delays skeletal muscle aging through SIRT1 pathway

被引：10
作者：
Zhu, Anni [1 ,2 ,3 ]
Duan, Zhiguang [1 ,2 ,3 ]
Chen, Yanru [3 ]
Zhu, Chenhui [1 ,2 ,3 ]
Fan, Daidi [1 ,2 ,3 ]
机构：
[1] Northwest Univ, Sch Chem Engn, Shaanxi Key Lab Degradable Biomed Mat, Xian 710069, Shaanxi, Peoples R China
[2] Northwest Univ, Shaanxi R&D Ctr Biomat & Fermentat Engn, Sch Chem Engn, Xian 710069, Shaanxi, Peoples R China
[3] Northwest Univ, Biotech & Biomed Res Inst, Xian 710069, Shaanxi, Peoples R China
来源：
PHYTOMEDICINE | 2023年 / 118卷
基金：
中国国家自然科学基金;
关键词：
Ginsenoside Rh4; Skeletal muscle aging; Mitochondrial dysfunction; SIRT1; MITOCHONDRIAL; RESPIRATION; SENESCENCE; EXPRESSION; NAD(+); GENE;
D O I：
10.1016/j.phymed.2023.154906
中图分类号：
Q94 [植物学];
学科分类号：
071001 ;
摘要：
Background: The aging of skeletal muscle is the leading cause of physical disability in older adults, currently effective treatment methods are lacking. Ginsenoside Rh4, an active component extracted from ginseng, pos-sesses beneficial anti-inflammatory and anti-oxidative effects. Purpose: The aim of this study was to elucidate the antioxidant effect of ginsenoside Rh4 on aging skeletal muscle and its molecular mechanism of anti-aging of skeletal muscle. Study design: In this study, we employed a D-galactose-induced model of skeletal muscle aging to investigate whether ginsenoside Rh4 can delay the process of skeletal muscle senescence. Methods: The effects of ginsenoside Rh4 on oxidative damage and inflammation in aging skeletal muscle were analyzed using immunofluorescence, immunohistochemistry, ELISA kits, H& E staining, flow cytometry, and protein immunoblotting. The changes of ginsenoside Rh4 on mitochondrial morphology were observed by transmission electron microscopy, and ELISA kits and protein immunoblotting analyzed the effects of ginsenoside Rh4 on mitochondrial homeostasis in skeletal muscle cells. The influence of ginsenoside Rh4 on the SIRT1 signaling pathway in aging skeletal muscle were investigated by protein immunoblotting, immunofluorescence, and beta-galactosidase staining. Results: Our results showed that Rh4 improved the morphology of muscle fibers and produced an anti-inflammatory response. Furthermore, in vitro experiments indicated that ginsenosides reduced the production of senescent cells, while Rh4 effectively alleviated oxidative damage in skeletal muscle and restored mito-chondrial balance. Transcriptome analysis and molecular docking showed that Rh4 improved mitochondrial homeostasis and delayed skeletal muscle aging by regulating the PGC-1 alpha-TFAM and HIF-1 alpha-c-Myc pathways via targeting SIRT1. Conclusion: Ginsenoside Rh4 improves oxidative stress and inflammation in skeletal muscle by activating SIRT1, deacetylating Nrf2, regulating PGC-1 alpha-TFAM and HIF-1 alpha-c-Myc pathways, and enhancing mitochondrial ho-meostasis, thus achieving the effect of delaying skeletal muscle aging.
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页数：11
相关论文
共 41 条
[1]   SIRT1 Controls the Transcription of the Peroxisome Proliferator-activated Receptor-γ Co-activator-1α (PGC-1α) Gene in Skeletal Muscle through the PGC-1α Autoregulatory Loop and Interaction with MyoD [J].
Amat, Ramon ;
Planavila, Anna ;
Chen, Shen Liang ;
Iglesias, Roser ;
Giralt, Marta ;
Villarroya, Francesc .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (33) :21872-21880
[2]   Cytochrome C Oxidase Subunit 4 (COX4): A Potential Therapeutic Target for the Treatment of Medullary Thyroid Cancer [J].
Bikas, Athanasios ;
Jensen, Kirk ;
Patel, Aneeta ;
Costello, John ;
Reynolds, Sarah M. ;
Mendonca-Torres, Maria Cecilia ;
Thakur, Shilpa ;
Klubo-Gwiezdzinska, Joanna ;
Ylli, Dorina ;
Wartofsky, Leonard ;
Burman, Kenneth ;
Vasko, Vasyl .
CANCERS, 2020, 12 (09) :1-15
[3]   Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds [J].
Bonkowski, Michael S. ;
Sinclair, David A. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2016, 17 (11) :679-690
[4]   An unexpected role for the transcriptional coactivator isoform NT-PGC-1α in the regulation of mitochondrial respiration in brown adipocytes [J].
Chang, Ji Suk ;
Ha, Kyoungsoo .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2017, 292 (24) :9958-9966
[5]  
Chen W.-J., 2021, INT J MOL SCI, V22
[6]  
Chen XX, 2022, LANCET, V400, P1967, DOI 10.1016/S0140-6736(22)01546-X
[7]   Sirt1 and Nrf2: regulation of Leydig cell oxidant/antioxidant intracellular environment and steroid formation [J].
Chung, Jin-Yong ;
Chen, Haolin ;
Zirkin, Barry .
BIOLOGY OF REPRODUCTION, 2021, 105 (05) :1307-1316
[8]   PGC-1α transcriptional response and mitochondrial adaptation to acute exercise is maintained in skeletal muscle of sedentary elderly males [J].
Cobley, J. N. ;
Bartlett, J. D. ;
Kayani, A. ;
Murray, S. W. ;
Louhelainen, J. ;
Donovan, T. ;
Waldron, S. ;
Gregson, W. ;
Burniston, J. G. ;
Morton, J. P. ;
Close, G. L. .
BIOGERONTOLOGY, 2012, 13 (06) :621-631
[9]   Ginsenoside Rh4 suppresses aerobic glycolysis and the expression of PD-L1 via targeting AKT in esophageal cancer [J].
Deng, Xuqian ;
Zhao, Jiaqi ;
Qu, Linlin ;
Duan, Zhiguang ;
Fu, Rongzhan ;
Zhu, Chenhui ;
Fan, Daidi .
BIOCHEMICAL PHARMACOLOGY, 2020, 178
[10]   Caveolin-1 is involved in high glucose accelerated human glomerular mesangial cell senescence [J].
Feng, Xin ;
Gao, Wei ;
Li, Yao .
KOREAN JOURNAL OF INTERNAL MEDICINE, 2017, 32 (05) :883-889
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