Ginsenoside Rh4 delays skeletal muscle aging through SIRT1 pathway

Anni Zhu; Zhiguang Duan; Yanru Chen; Chenhui Zhu; Daidi Fan

doi:10.1016/j.phymed.2023.154906

Ginsenoside Rh4 delays skeletal muscle aging through SIRT1 pathway

Phytomedicine. 2023 Sep:118:154906. doi: 10.1016/j.phymed.2023.154906. Epub 2023 May 29.

Authors

Anni Zhu¹, Zhiguang Duan¹, Yanru Chen², Chenhui Zhu³, Daidi Fan⁴

Affiliations

¹ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Research Institute, Northwest University, Xi'an, Shaanxi 710069, China.
² Biotech. & Biomed. Research Institute, Northwest University, Xi'an, Shaanxi 710069, China.
³ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Research Institute, Northwest University, Xi'an, Shaanxi 710069, China. Electronic address: zch2005@nwu.edu.cn.
⁴ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an, Shaanxi 710069, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an, Shaanxi 710069, China; Biotech. & Biomed. Research Institute, Northwest University, Xi'an, Shaanxi 710069, China. Electronic address: fandaidi@nwu.edu.cn.

PMID: 37354698
DOI: 10.1016/j.phymed.2023.154906

Abstract

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, possesses 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 β-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 mitochondrial balance. Transcriptome analysis and molecular docking showed that Rh4 improved mitochondrial homeostasis and delayed skeletal muscle aging by regulating the PGC-1α-TFAM and HIF-1α-c-Myc pathways via targeting SIRT1.

Conclusion: Ginsenoside Rh4 improves oxidative stress and inflammation in skeletal muscle by activating SIRT1, deacetylating Nrf2, regulating PGC-1α-TFAM and HIF-1α-c-Myc pathways, and enhancing mitochondrial homeostasis, thus achieving the effect of delaying skeletal muscle aging.

Keywords: Ginsenoside Rh4; Mitochondrial dysfunction; SIRT1; Skeletal muscle aging.

MeSH terms

Ginsenosides* / pharmacology
Molecular Docking Simulation
Muscle, Skeletal
Sirtuin 1

Substances

ginsenoside Rh4
Ginsenosides
Sirtuin 1