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Juzentaihoto Suppresses Muscle Atrophy and Decreased Motor Function in SAMP8 Mice
Yasuyo Morita1, Tomoaki Ishida1, Shumpei Morisawa1,2
1Department of Pharmacy, Kochi Medical School Hospital.
Abstract:
Sarcopenia is a disease whose symptoms include decreased muscle mass and weakened muscle strength with age. In sarcopenia, decreased production of insulin-like growth factor-1 (IGF-1) increases ubiquitin ligases, such as Atrogin1 and Muscle RING-Finger Protein-1 (MuRF1), by activating forkhead box O (FOXO), and inflammatory cytokines and oxidative stress increase the expression of ubiquitin ligases by activating the transcription factor nuclear factor-kappa B (NF-κB). In addition, increased levels of ubiquitin ligases cause skeletal muscle atrophy. Conversely, sirtuin 1 (Sirt1) is known to regulate the expression of ubiquitin ligases by suppressing the activities of NF-κB and FOXO. In this study, we evaluated the effect that juzentaihoto hot water extract (JTT) has on skeletal muscle atrophy and motor function by administering it to senescence-accelerated mouse prone-8 (SAMP8). The group treated with JTT displayed larger gastrocnemius muscle (GA) and extensor digitorum longus (EDL) weights, larger GA muscle fiber cross-sectional areas, and motor function decline during rota-rod tests. JTT also increased IGF-1 serum levels, as well as mRNA Sirt1 levels in GA. Serum levels of tumor necrosis factor-α, interleukin-6, and mRNA levels of Atrogin1 and MuRF1 in GA were reduced by JTT. The muscle fiber cross-sectional area of GA was correlated with the mRNA levels of Sirt1 in GA. The results of this study suggested that JTT administration suppresses skeletal muscle atrophy and motor function decline in SAMP8 mice. This effect may be associated with the increased expression levels of Sirt1 and IGF-1 by JTT.
Insights
Juzentaihoto hot water extract (JTT) improved skeletal muscle mass and function in aging mice by increasing Sirt1 and IGF-1 levels, reducing muscle atrophy markers.
Area of Science:
- Gerontology
- Muscle Physiology
- Pharmacology
Background:
- Sarcopenia, characterized by age-related muscle mass and strength loss, involves increased ubiquitin ligases (Atrogin1, MuRF1) via FOXO and NF-κB pathways.
- Sirtuin 1 (Sirt1) counteracts muscle atrophy by suppressing NF-κB and FOXO.
- Insulin-like growth factor-1 (IGF-1) production decreases with age, contributing to sarcopenia.
Purpose of the Study:
- To investigate the effects of juzentaihoto hot water extract (JTT) on age-related skeletal muscle atrophy and motor function.
- To explore the underlying molecular mechanisms of JTT's action in senescence-accelerated mouse prone-8 (SAMP8) models.
Main Methods:
- Administration of JTT to SAMP8 mice.
- Assessment of gastrocnemius (GA) and extensor digitorum longus (EDL) muscle weights and fiber cross-sectional areas.
- Evaluation of motor function using rota-rod tests.
- Measurement of serum IGF-1, tumor necrosis factor-α, and interleukin-6 levels.
- Quantification of Sirt1, Atrogin1, and MuRF1 mRNA expression in GA muscle.
Main Results:
- JTT treatment increased GA and EDL muscle weights and GA muscle fiber cross-sectional area.
- JTT administration improved motor function in SAMP8 mice.
- JTT elevated serum IGF-1 and GA Sirt1 mRNA levels, while reducing inflammatory cytokines and Atrogin1/MuRF1 mRNA expression.
- GA muscle fiber cross-sectional area positively correlated with GA Sirt1 mRNA levels.
Conclusions:
- JTT effectively suppresses skeletal muscle atrophy and motor function decline in SAMP8 mice.
- The beneficial effects of JTT are likely mediated by increased Sirt1 and IGF-1 expression, alongside reduced ubiquitin ligase activity.
