Graduate School of Integrated Arts and Sciences, Kochi University, 185-1 Kohasu, Oko-cho, Nankoku, Kochi, Japan.
Department of Pharmacy, Kochi Medical School Hospital, 185-1 Kohasu, Oko-cho, Nankoku, Kochi, Japan.
J Nat Med. 2022 Mar;76(2):379-388. doi: 10.1007/s11418-021-01590-2. Epub 2022 Jan 8.
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.
肌少症性肥胖与内脏脂肪增加和肌肉量减少有关，导致胰岛素敏感性降低、炎症细胞因子产生增加和氧化应激。在这项研究中，我们首先评估了草药对 Sirtuin 1（sirt1）启动子转录活性的体外影响，作为其治疗效果的指标。我们的数据表明，热水 Saikokeishikankyoto（SKK）提取物在体外增加了 sirt1 转录活性，将其鉴定为候选治疗药物，可在 KKAy 型 2 型糖尿病肥胖小鼠模型中进行评估。这些体内评估表明，SKK 治疗增加了比目鱼肌（GA）横截面上的湿重和肌纤维含量，并恢复了这些动物的运动功能。此外，SKK 治疗降低了血清中的肿瘤坏死因子-α（TNFα）表达，并抑制了 GA 样本中的 Atrogin1 和 MuRF1 转录。这种治疗还增加了这些组织中的 sirt1 表达。这些结果表明，SKK 通过抑制炎症抑制 KKAy 小鼠的骨骼肌萎缩并改善运动功能。在实际的临床实践中，SKK 有望抑制肌少症性肥胖患者的肌肉萎缩并改善运动功能障碍。
