Saikokeishikankyoto extract alleviates muscle atrophy in KKAy mice

Yanglan Ou,Kei Kawada,Shumpei Morisawa,Hiroko Fujita,Kohei Jobu,Tomoaki Ishida,Saburo Yoshioka,Mitsuhiko Miyamura

doi:10.1007/s11418-021-01590-2

Yanglan Ou, Kei Kawada + Show 6 more

Open Access

https://doi.org/10.1007/s11418-021-01590-2

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Abstract

Sarcopenic obesity is associated with increased visceral fat and decreased muscle mass, resulting in decreased insulin sensitivity, increased production of inflammatory cytokines, and oxidative stress. In this study, we first evaluated the effects of herbal medicines on the transcriptional activity of the Sirtuin 1 (sirt1) promoter in vitro as an indicator of their therapeutic effect. Our data suggested that hot water Saikokeishikankyoto (SKK) extracts increased sirt1 transcriptional activity in vitro, identifying it as a candidate therapeutic for evaluation in the KKAy type 2 diabetic obesity mouse model. These in vivo evaluations revealed that SKK treatment increased the wet weight and muscle fiber content in cross sections of the gastrocnemius muscle (GA) and restored motor function in these animals. In addition, SKK treatment reduced tumor necrosis factor-α (TNFα) expression in the sera and suppressed Atrogin1 and MuRF1 transcription in the GA samples. This treatment also increased sirt1 expression in these tissues. These results suggest that SKK inhibits skeletal muscle atrophy and improves motor function in KKAy mice by suppressing inflammation. In actual clinical practice, SKK is expected to inhibit muscle atrophy and improve motor dysfunction in sarcopenic obesity.Graphical abstract

Highlights

Materials and methodsSarcopenic obesity is associated with increased visceral fat and decreased muscle mass [1, 2], and decreases the patient's motor function and significantly reduces quality of life [3, 4]
This assay allowed us to evaluate the transcriptional activity of the sirt1 promoter under these conditions and showed that both the SKK and Rikkosan hot water extracts induced an almost 200% increase in sirt1 promoter activity compared to the control
We evaluated the effects of SKK and crude drugs consist of SKK in C2C12 cells using a luciferase assay. sirt1 promoter activities were significantly higher in the 100 μg/ml SKK (P < 0.05), 1000 μg/mL SKK (P < 0.01), and resveratrol groups (P < 0.01) when compared to the control (Fig. 2a)

Summary

Materials and methods

Sarcopenic obesity is associated with increased visceral fat and decreased muscle mass [1, 2], and decreases the patient's motor function and significantly reduces quality of life [3, 4]. Several studies have reported that various substances increase Sirtuin (sirt1) expression and exert an inhibitory effect on muscle atrophy [19, 20]. Hot water extracts of 62 herbal medicines [27] were provided to our group from Tsumura (Tokyo, Japan) as spray dried products. U and the extract was added to C2C12 cells at a concentration of 1.0 × 10–4 U/ml These data were expressed as mean ± SD (n = 4), and evaluated by one way ANOVA, and followed by Bonferroni test. QRT-PCR was performed using the Step One Plus Real-Time PCR System (Applied Biosystems, CA, USA) and the mRNA expression levels of sirtuin (sirt1) and ubiquitin ligases (murf and atrogin1) were evaluated using GAPDH as the internal reference standard. Statistical analysis was performed using the Stat Flex program (View Flex, Tokyo, Japan) and statistical significance was set at P < 0.05

Results

Discussion

Conclusion