技術摘要

Sarcopenia is an aging associated involving skeletal muscle atrophy and reduction in muscle strength; and there are no pharmaceutical interventions available so far. Moreover, conditions like hyperglycaemia are known to further intensify muscle degradation. Therefore, novel strategies to attenuate skeletal muscle loss are essential to enhance muscle function and thereby to improve the quality of life in diabetic individuals. In this study we have investigated the efficiency of a soybean peptide fraction APPH and a short peptide from PP622 named DI-10 for their cytoprotective effects in skeletal muscle cells. PP622 and DI-10 treatment in C2C12 cells showed dose dependent activation of Akt/mtor signalling pathway that is involved in skeletal myogenesis. According to Western blotting analysis, PP622 and DI-10 induced the phosphorylation of Akt, mTOR proteins and induced myogenic differentiation of C2C12 myoblasts in a differentiation medium. The phosphorylation myogenic transcription factor Foxo3A was also found to be increased in the cells treated with PP622 and DI-10. In addition, reduction in cell viability caused by high glucose was also found to be reduced when treated with different doses of high glucose in a dose dependent manner. Moreover, number of myotybules in a differentiation medium reduced upon high glucose challenge, but treatment with PP622 increased the number of differentiated myotubules. Further, the phosphorylations of AMPK and mitochondrial-related transcription factors such as PGC-1α were suppressed upon high glucose challenge but PP622 and DI-10 treatment restored the protein levels. We demonstrate for the first time that a specific potato peptide has a therapeutic effect against sarcopenia. In addition, DI-10 and PP622 improved the myogenic differentiation and their mitochondrial biogenesis and further improved mygenic protein and inhibited muscle protein degradation in C212 cells challenged under high glucose condition.

肌少症是與老化相關的疾病，涉及骨骼肌萎縮和肌力減少；目前尚無有效的藥物治療方法。此外，像是高血糖等情況已知會進一步加劇肌肉退化。因此，開發新的策略來減緩骨骼肌損失對於提高肌肉功能並改善糖尿病患者的生活品質至關重要。在本研究中，我們探討了大豆肽分子APPH和PP622中短肽DI-10在骨骼肌細胞中的細胞保護效應。PP622和DI-10在C2C12細胞中的處理顯示出劑量依賴性地激活了涉及骨骼肌生成的Akt/mTOR信號通路。根據Western blot分析，PP622和DI-10誘導了Akt、mTOR蛋白的磷酸化，並在分化培養基中促進了C2C12肌母細胞的肌源性分化。在處理過PP622和DI-10的細胞中，我們還發現肌源性轉錄因子Foxo3A的磷酸化水準也有所增加。此外，在高糖挑戰下，細胞活力的下降被發現隨著不同劑量的高糖處理呈劑量依賴性減少。更重要的是，在分化培養基中，經高糖挑戰後，肌管數量減少，但PP622處理後，分化肌管的數量有所增加。此外，AMPK的磷酸化及與線粒體相關的轉錄因子如PGC-1α在高糖挑戰下被抑制，但PP622和DI-10的處理恢復了這些蛋白質的水平。我們首次證明了特定的馬鈴薯肽對抗肌少症的治療效果。此外，DI-10和PP622改善了肌源性分化、線粒體生物生成，並進一步改善了肌源性蛋白質，抑制了在高糖環境下C2C12細胞中的肌肉蛋白降解。

現有技術描述、問題及其缺陷

Sarcopenia is an aging associated involving skeletal muscle atrophy and reduction in muscle strength; and there are no pharmaceutical interventions available so far.

肌少症是與老化相關的疾病，涉及骨骼肌萎縮和肌力減少；目前尚無有效的藥物治療方法。

產業應用性

It can be used in the health food and pharmaceutical composition industries.

本技術發明之目的及達成功效

The novel active peptides disclosed in the present invention can be derived from natural plants (Potato), can also be mass-produced through biotechnology, and have good effects. Therefore, in addition to being used as medicines, they can also be developed into Functional foods.

本發明所揭示的創新活性肽可以來自天然植物（如馬鈴薯），並且可以通過生物技術進行大規模生產，具有良好的效果。因此，除了用作藥物外，還可以開發為功能性食品。

相關專利資訊

1.     DI-10 and PP622 effectively improve on muscle Protein synthesis mechanism 2.     DI-10 and PP622 accelerates Microtubule formation in differentiation media within 48 h 3.     DI-10 and PP622 improves the viability of C2C12 cells under High glucose stress 4.     DI-10 and PP622 improves myotubes differentiation as they can enhance muscle protein markers 5.     DI-10 and PP622 ameliorates High glucose associated modulations in protein synthesis and mitochondrial biogenesis in C2C12 cell viability 6.     DI-10 and PP622 improves the expression of mitochondrial biogenesis-regulating factors in myotubes 7.     DI-10 and PP622 Inhibits GSK3β thereby facilitates myogenic differentiation 8.     DI-10 and PP622 protects against High glucose induced muscle atrophy by downregulation of atrogin1/MAFbx and MuRF1 9.     DI-10 and PP622 ameliorates High glucose associated modulations in protein synthesis in C2C12 cell viability