Sarcopenia is an age‐related muscle atrophy syndrome characterized by the loss of muscle strength and mass. Although many agents have been used to treat sarcopenia, there are no successful treatments to date. In this study, we identified Danshensu sodium salt (DSS) as a substantial suppressive agent of muscle atrophy. We used a D‐galactose (DG)‐induced aging‐acceleration model, both in vivo and in vitro, to confirm the effect of DSS on sarcopenia. DSS inhibits the expression of muscle atrophy‐related factors (MuRF1, MAFbx, myostatin, and FoxO3a) in DG‐induced mouse C2C12 and human skeletal muscle cells. Additionally, DSS restored the diameter of reduced C2C12 myotubes. Next, we demonstrated that DSS stimulates AMPK and PGC1α through CaMKII. DSS inhibits the translocation of FoxO3a into the nucleus, thus inhibiting muscle atrophy in a calcium‐dependent manner. DSS initiated the protein–protein interaction between FoxO3a and PGC1α. The reduction of the PGC1α‐FoxO3a interaction by DG was restored by DSS. Also, DSS suppressed increased intracellular reactive oxygen species (ROS) by DG. In animal models, DSS administration improved mouse muscle mass and physical performance (grip strength and hanging test) under DG‐induced accelerated aging conditions. These findings demonstrated that DSS attenuates muscle atrophy by inhibiting the expression of muscle atrophy‐related factors. Therefore, DSS may be a potential therapeutic agent for the treatment of sarcopenia.

Background: Cancer‐associated cachexia (CAC) is a multifactorial syndrome characterised by progressive loss of muscle mass with limited Food and Drug Administration treatments. Although emerging evidence suggests that l‐leucine and β‐hydroxy‐β‐methyl butyrate (HMB) have potential for treating CAC, the role of α‐ketoisocaproate (KIC), a metabolite of l‐leucine, remains unclear. Therefore, this study explored the use of KIC as a therapeutic agent for CAC‐induced muscle atrophy by targeting myostatin.Methods: We evaluated the effect of KIC on muscle atrophy using BALB/c mice and C2C12 myotubes as models of C26‐ and 4T1‐induced CAC. Male and female mice were injected with C26 and 4T1 cells, respectively. Grip strength was measured weekly, and mice were sacrificed 4 weeks post‐injection for muscle collection. C2C12 myotubes were treated with conditioned media (CM) derived from C26 or 4T1 cells.Results: KIC suppressed mRNA expression of myostatin, a key regulator of muscle atrophy, more effectively than did l‐leucine (−26.37 ± 4.11%, p < 0.01). KIC enhanced protein turnover in C2C12 myotubes and maintained 50% cell viability at high concentrations (KIC: 4.68 mM, HMB: 3.11 mM). Following CM treatment, KIC suppressed MuRF1 and MAFbx expression in a myostatin‐dependent manner, thereby reducing their polyubiquitination. KIC restored Akt‐FoxO3a phosphorylation, leading to improved myotube diameter (+63.8 ± 25.71%, p < 0.05) and fusion index (+51.9 ± 22.6%, p < 0.05). Immunofluorescence and nuclear fractionation revealed that KIC reduced FoxO3a nuclear accumulation. CM reduced p‐Akt–FoxO3a interaction, which was rescued by KIC. In vivo, KIC administration increased body weight (11.11 ± 8.53%), grip strength (24.76 ± 10.58%), and skeletal muscle mass (p < 0.001) in C26 tumour‐bearing mice. Protein expression of myostatin in the tibialis anterior (TA) muscle (−23.57 ± 12.22%, p < 0.05) and serum (−52.11 ± 3.56%, p < 0.001) was lower in KIC‐treated mice (n = 12) compared with that in the controls. KIC increased the mean fibre cross‐sectional area in TA (24.51 ± 14.14%, p < 0.01). In 4T1 tumour‐bearing mice, KIC improved body weight (13.10 ± 10.76%) and grip strength (7.42 ± 4.33%) (p < 0.001, n = 10). Serum myostatin levels (−57.43 ± 9.46%, p < 0.001) and skeletal muscle weight were reduced in KIC‐treated mice (n = 10).Conclusion: Our findings demonstrate that KIC improves muscle function in CAC‐induced muscle atrophy by regulating myostatin expression in skeletal muscle via the Akt–FoxO3a pathway. Thus, KIC has been proposed as a potential therapeutic agent against CAC.

This study presents the synthesis and comprehensive characterization of ketoprofen 1,4-sorbitan ester, a novel compound with potential applications in drug delivery. The compound was synthesized through a two-step process involving the acid-catalyzed dehydration of D-Glucose to form 1,4-sorbitan, followed by esterification with ketoprofen. The structures of ketoprofen 1,4-sorbitan ester and the reference compound, ketoprofen methyl ester, were rigorously analyzed using a combination of advanced analytical techniques. High-resolution accurate mass liquid chromatography–mass spectrometry was used to determine the precise molecular mass and elemental composition of the synthesized compounds. ¹H and ¹³C nuclear magnetic resonance spectroscopy provided detailed information on the molecular structure and atomic connectivity to identify the specific functional groups and confirm the formation of ester bonds.