Gui Qi Zhuang Jin Decoction ameliorates mitochondrial dysfunction in sarcopenia mice via AMPK/PGC-1α/Nrf2 axis revealed by a metabolomics approach.

OBJECTIVE: Sarcopenia, as a condition of muscle mass loss and functional decline typically diagnosed in elderly individuals, severely affects human physical activity, metabolic homeostasis, and quality of life. Gui Qi Zhuang Jin Decoction (GQZJD), an approved hospital-based prescription with years of clinical application, has been demonstrated to have a notable therapeutic effect on sarcopenia. However, its potential mechanism of action in the treatment of sarcopenia remains uncertain. METHODS: Ultra-performance liquid chromatography paired with Q Exactive™ HF-X mass spectrometry (UPLC-QE-MS) was used to identify the ingredients of GQZJD. Subsequently, GQZJD observed the basic growth and muscles of the sarcopenia mouse, while the behavioral indicators were also tested. Muscle histopathology and serum oxidative stress biochemicals were also detected, and mitochondrial function and energy metabolism-related indicators in the gastrocnemius muscle were examined. Then, a metabolomics strategy was applied to predict possible pathways involving mitochondria by which GQZJD could improve sarcopenia. Finally, quantitative real-time polymerase chain reaction and western blot analyses were carried out to validate the effects of GQZJD on sarcopenia-induced mitochondrial dysfunction, together with uncovering the associated mechanisms. RESULTS: Twenty-seven ingredients absorbed into the blood (IAIBs) of GQZJD were identified using UPLC-QE-MS, which were regarded as the main active ingredients behind its sarcopenia treatment effects. GQZJD administration increased the body weight, gastrocnemius muscle mass, and autonomic activity, mitigated muscle tissue morphology and pathology; and alleviated the oxidative stress levels in sarcopenia mice. Treatment with GQZJD also decreased the mitochondrial reactive oxygen species level and serum lipid peroxide Malonaldehyde concentration. and increased the mitochondrial membrane potential, adenosine triphosphate level, 8­hydroxy-2-deoxyguanosine content, mitochondrial DNA copy number, and the mitochondrial fission factor dynamin-related protein 1. Non-targeted metabolomics suggested that the sarcopenia therapeutic effect of GQZJD on sarcopenia may occur through the glycerophospholipid metabolism, choline metabolism in cancer, phenylalanine metabolism and tyrosine metabolism pathways, implying an association with AMP-activated protein kinase (AMPK) and related signals. Further, the molecular docking results hinted that AMPK performed well in terms of binding energy with the 27 IAIBs of GQZJD (average binding energy, -7.5 kcal/mol). Finally, we determined that GQZJD significantly activated the key targets of the AMPK/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis.. CONCLUSIONS: Our results demonstrated that GQZJD ameliorated d-galactose-induced sarcopenia by promoting the animal behaviours, facilitating mitochondrial function and restoring mitochondrial energy metabolism. with its effects mediated by the AMPK/PGC-1α/Nrf2 axis. Over all, GQZJD represents a promising therapeutic candidate that ameliorated sarcopenia in aging mice.

Advances in the study of plant-derived extracellular vesicles in the skeletal muscle system.

Plant-derived extracellular vesicles (PDEV) constitute nanoscale entities comprising lipids, proteins, nucleic acids and various components enveloped by the lipid bilayers of plant cells. These vesicles play a crucial role in facilitating substance and information transfer not only between plant cells but also across different species. Owing to its safety, stability, and the abundance of raw materials, this substance has found extensive utilization in recent years within research endeavors aimed at treating various diseases. This article provides an overview of the pathways and biological characteristics of PDEV, along with the prevalent methods employed for its isolation, purification, and storage. Furthermore, we comprehensively outline the therapeutic implications of diverse sources of PDEV in musculoskeletal system disorders. Additionally, we explore the utilization of PDEV as platforms for engineering drug carriers, aiming to delve deeper into the significance and potential contributions of PDEV in the realm of the musculoskeletal system.

Causal associations between sarcopenia-related traits and intervertebral disc degeneration: a two-sample mendelian randomization analysis.

BACKGROUND: Sarcopenia (SP) and intervertebral disc degeneration (IVDD) have a higher incidence in the elderly population. Previous studies have indicated a potential association between SP and IVDD. The objective of this study is to elucidate the potential causal relationship between sarcopenia-related traits and IVDD through Two-sample Mendelian randomization (MR) analysis. METHODS: We utilized a genome-wide association study conducted on the European population to collect aggregated data on sarcopenia and IVDD. Inverse variance weighting was primarily employed, supplemented by MR Egger, weighted median, simple model, and weighted model methods. Additionally, sensitivity analysis was performed to assess the robustness of the findings. RESULTS: Appendicular lean mass is positively associated with "Other intervertebral disc disorders" (OIDD) and "Prolapsed or slipped disc" (POSD) (OIDD: p = 0.002, OR = 1.120; POSD: p < 0.001, OR = 1.003), while grip strength (GS) is positively associated with POSD (left: p = 0.004, OR = 1.008; right: p < 0.001, OR = 1.010). It is worth mentioning that walking pace has significant causal relationship with "Low back pain" (LBP), "Lower back pain or/and sciatica" (LBPOAS), "Sciatica with lumbago" (SWL) and OIDD (LBP: p < 0.001, OR = 0.204; LBPOAS: p < 0.001, OR = 0.278; SWL: p = 0.003, OR = 0.249; OIDD: p < 0.001, OR = 0.256). CONCLUSION: The present study revealed the causal relationship between SP-related traits and IVDD and recommended to prevent and treat sarcopenia as a means of preventing IVDD in clinic practice.