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. 2024 Jan 3;16(1):157.
doi: 10.3390/nu16010157.

Ashwagandha Ethanol Extract Attenuates Sarcopenia-Related Muscle Atrophy in Aged Mice

Jin-Sung Ko  1 , Bo-Yoon Chang  2 , Young-Ju Choi  1 , Ji-Soo Choi  3 , Hee-Yeon Kwon  3 , Jae-Yeon Lee  3 , Sung-Yeon Kim  2 , Se-Young Choung  4
Affiliations

Ashwagandha Ethanol Extract Attenuates Sarcopenia-Related Muscle Atrophy in Aged Mice

Jin-Sung Ko et al. Nutrients. .

Abstract

The investigation focused on the impact of Withania somnifera (ashwagandha) extract (WSE) on age-related mechanisms affecting skeletal muscle sarcopenia-related muscle atrophy in aged mice. Beyond evaluating muscular aspects, the study explored chronic low-grade inflammation, muscle regeneration, and mitochondrial biogenesis. WSE administration, in comparison to the control group, demonstrated no significant differences in body weight, diet, or water intake, affirming its safety profile. Notably, WSE exhibited a propensity to reduce epidermal and abdominal fat while significantly increasing muscle mass at a dosage of 200 mg/kg. The muscle-to-fat ratio, adjusted for body weight, increased across all treatment groups. WSE administration led to a reduction in the pro-inflammatory cytokines TNF-α and IL-1β, mitigating inflammation-associated muscle atrophy. In a 12-month-old mouse model equivalent to a 50-year-old human, WSE effectively preserved muscle strength, stabilized grip strength, and increased muscle tissue weight. Positive effects were observed in running performance and endurance. Mechanistically, WSE balanced muscle protein synthesis/degradation, promoted fiber differentiation, and enhanced mitochondrial biogenesis through the IGF-1/Akt/mTOR pathway. This study provides compelling evidence for the anti-sarcopenic effects of WSE, positioning it as a promising candidate for preventing sarcopenia pending further clinical validation.

Keywords: Withania somnifera extract; in vitro; in vivo; muscle atrophy; sarcopenia.

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Conflict of interest statement

Author Ji-Soo Choi, Hee-Yeon Kwon, Jae-Yeon Lee were employed by the company NSTbio Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
HPLC chromatogram of WSE and chemical structure of withanolide A. (A) withanolide A; (B) WSE; and (C) the structure of withanolide A.
Figure 2
Figure 2
Effect of WSE on muscle performance in aged mice. (A) Body weight curves. (B) Food intake curves. (C) ALT and AST. (D) Grip strength curves. (E) Running time. (F) Distance to exhaustion time. The data are shown as mean ± SE; n = 9. * p < 0.05, ** p < 0.01, *** p < 0.001 versus the CON group.
Figure 3
Figure 3
Effect of WSE on cytokine levels in aged mice. (A) Serum cytokine levels. (B) Expression levels of cytokine mRNA in the gastrocnemius. The data are shown as mean ± SE; n = 9. * p < 0.05, ** p < 0.01, *** p < 0.001 versus the CON group.
Figure 4
Figure 4
Effect of WSE on muscle, fat tissue mass, and myofiber cross-sectional area (CSA) in aged mice. The skeletal muscle mass of the (A) quadriceps, (B) soleus, and (C) gastrocnemius. The fat mass of (D) epidermal fat and (E) abdominal fat. It was shown as a ratio to the body weight (%). (F) Representative images of an H&E-stained gastrocnemius. (G) The distribution graph of muscle fiber CSA (%). The data are shown as mean ± SE; n = 9. * p < 0.05 versus the CON group.
Figure 5
Figure 5
Effect of WSE on muscle protein synthesis and proteolysis through the AKT/mTOR pathway in aged mice. (A) Western blot images of IGF, AKT, and mTOR. (B) Relative protein expression of IGF, p-AKT/t-AKT, and p-mTOR/t-mTOR. (C) Western blot images of MyoD and Myogenin. (D) Relative protein expression of MyoD and Myogenin. (E) Western blot images of MuRF1 and FOXO3a. (F) Relative protein expression of MuRF1 and p-FOXO3a/t-FOXO3a. (G) Relative mRNA expression of Myogenin, MyoD, MuRF1, Myostatin, and Atrogin-1. The data are shown as mean ± SE; n = 6. * p < 0.05, ** p < 0.01 versus the CON group.
Figure 6
Figure 6
Effect of WSE on mitochondrial biogenesis through the Sirt1/PGC-1α pathway in aged mice. (A) Western blot images of Sirt1 and PGC-1α. (B) Relative protein expression of SIRT1 and PGC-1α. (C) Relative mRNA expression of Sirt1 and PGC-1α. The data are shown as mean ± SE; n = 6. * p < 0.05 versus the CON group.
Figure 7
Figure 7
Effect of WSE on cell viability and myotube atrophy in C2C12 myotubes. (A) Cell viability following WSE treatment in C2C12 cells. (B) Changes in myotube diameter after WSE treatment of C2C12 cells with dexamethasone (DEX)-induced muscle atrophy. The data are shown as mean ± SE. # p < 0.05, ## p < 0.01, ### p < 0.001 versus the CON group, * p < 0.05, ** p < 0.01, *** p < 0.001 versus the DEX group.
Figure 8
Figure 8
Effect of WSE on muscle protein synthesis and protein degradation through the PI3K/AKT pathway in dexamethasone-induced C2C12 muscle atrophy. The protein expression level of (A) mTOR, PI3K, and AKT, (B) MyoD and Myogenin, (C) FOXO3a, Myostatin, Atrogin-1, and MuRF1, (E) Sirt1 and PGC1α. (D) Relative mRNA level of Myostatin, Atrogin-1, and MuRF1. The data are shown as mean ± SE. ## p < 0.01, ### p < 0.001 versus the CON group, * p < 0.05, ** p < 0.01, *** p < 0.001 versus the DEX group.
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References

    1. Cruz-Jentoft A.J., Sayer A.A. Sarcopenia. Lancet. 2019;393:2636–2646. doi: 10.1016/S0140-6736(19)31138-9. - DOI - PubMed
    1. Cho M.R., Lee S. A Review of Sarcopenia Pathophysiology, Diagnosis, Treatment and Future Direction. J. Korean Med. Sci. 2022;37:e146. doi: 10.3346/jkms.2022.37.e146. - DOI - PMC - PubMed
    1. Nascimento C.M., Ingles M., Salvador-Pascual A., Cominetti M.R., Gomez-Cabrera M.C., Viña J. Sarcopenia, frailty and their prevention by exercise. Free. Radic. Biol. Med. 2019;132:42–49. doi: 10.1016/j.freeradbiomed.2018.08.035. - DOI - PubMed
    1. Yuan S., Larsson S.C. Epidemiology of sarcopenia: Prevalence, risk factors, and consequences. Metabolism. 2023;144:155533. doi: 10.1016/j.metabol.2023.155533. - DOI - PubMed
    1. Pan L., Xie W., Fu X., Lu W., Jin H., Lai J., Zhang A., Yu Y., Li Y., Xiao W. Inflammation and sarcopenia: A focus on circulating inflammatory cytokines. Exp. Gerontol. 2021;154:111544. doi: 10.1016/j.exger.2021.111544. - DOI - PubMed

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