肌少症是指隨著年齡增長而骨骼肌質量與強度下降的綜合症，不只影響老年人的身體健康與行動能力，還會增加跌倒風險、認知功能障礙並造成死亡。目前臨床預防與延緩肌少症方式為增加運動與攝取營養食品。Oligonol是一種以荔枝果實為原料萃取，經過特殊剪裁製成的寡酚，並與兒茶素形成穩定且容易吸收之結構。本實驗室先前研究證實，oligonol透過調控mTOR/SREBP-1減少高脂飲食小鼠肝臟和骨骼肌組織中脂質含量，改善其胰島素抗性；Oligonol透過抑制轉錄因子NFκB以及調控粒線體生合成，減低糖尿病小鼠發生腎臟損傷之併發症，並可抑制肌肉萎縮基因MuRF1與Atrogin-1，改善糖尿病肌肉萎縮之情形。然而，oligonol對於改善老化相關肌少症的功效仍尚付闕如。本研究利用老化促進小鼠(Senescence-Accelerated Mouse, SAM)來探討oligonol改善老化相關肌少症之功效及其分子機轉。實驗組別分為SAMR1 (SAM resistant 1)、SAMP8 (SAM prone 8)以及SAMP8餵食oligonol (200 mg/kg diet) 8週，測量握力之後犧牲，取小鼠的脛骨前肌與腓腸肌，進行組織切片、蛋白質和RNA分析。結果顯示，40週齡SAMP8小鼠的腓腸肌重量、四肢握力、腓腸肌纖維截面積相較於SAMR1皆顯著下降(p < 0.05)，餵食oligonol可以顯著提升SAMP8小鼠腓腸肌重量、四肢握力、腓腸肌纖維截面積，減緩肌肉萎縮。進一步探討分子機制，oligonol透過活化PI3K /AKT /mTOR /p70S6K訊息途徑增加肌肉蛋白合成(protein synthesis)，並抑制FoxO1a進入細胞核，降低MuRF1與Atrogin-1基因轉譯，減緩肌肉通過泛素-蛋白酶體 (ubiquitin-proteasome system)所造成的蛋白質降解(protein degradation)。同時oligonol降低Atg13, LC3, p62等自噬作用相關蛋白表達，減緩自噬-溶酶體系統(autophagy-lysosome system)介導的肌肉蛋白降解。
老化過程中會逐漸失去粒線體更新及汰舊的能力並產生大量活性氧(reactive oxygen species, ROS)。本研究發現，40週齡SAMP8小鼠骨骼肌負責調控粒線體生合成與融合/分裂基因相較於SAMR1顯著降低。餵食oligonol可以提高粒線體生合成相關基因(PGC1α、Tfam、Ndufs8)與融合相關基因(Mfn2與Opa1)表達，進而恢復粒線體生合成與融合之能力。先前文獻指出促發炎介質(proinflammatory cytokine)會促使轉錄因子NFĸB進入細胞核，啟動肌肉萎縮基因與發炎基因轉譯。本研究發現餵食oligonol可抑制SAMP8小鼠轉錄因子NFĸB進入細胞核，降低MuRF1與Atrogin-1肌肉萎縮基因轉譯，並降低 IL1α、IL6、MCP-1、TGFβ發炎因子表達，減緩肌肉組織發炎與萎縮。
總結以上結果，oligonol可以增加骨骼肌蛋白質合成並降低蛋白質降解、改善粒線體生合成、融合與細胞自噬，減少發炎介質產生來減緩肌肉萎縮。本研究建議oligonol可作為改善老年人肌肉萎縮之膳食補充品。

The purpose of this study was to examine whether oligonol ameliorates aged-related muscle atrophy in Senescence-accelerated mouse (SAM) prone 8 (SAMP8). Oligonol, a low molecular weight polyphenol derived from lychee, has been known for anti-inflammatory, anti-cancer, anti-diabetic and anti-obesity properties. Sarcopenia is an aging-related symptom with a significant reduction in mass and strength of skeletal muscle. In this study, we investigated the effect of oligonol on aging-related muscle atrophy and its related signaling. SAMP8 and senescence accelerated mouse resistant 1 (SAMR1) are recognized as appropriate models for studying muscle aging. We used SAMR1 as positive control, SAMP8 as negative control and SAMP8 + oligonol as experimental group. Male SAMP8 were fed with regular diet supplemented with 200 mg oligonol /kg diet for eight weeks. Dietary supplement of oligonol for 8 wk led to increase in skeletal muscle mass, grip strength and cross-section area. Oligonol supplementation significantly up-regulated protein synthesis via phosphorylation of mTOR and p70S6K in SAMP8. Oligonol prevented nuclear translocation of NFκB and FoxO1a, thereby suppressing Atrogin-1 and MuRF1 expression. Oligonol reduced inflammatory mediators and inhibited autophagy by decreasing the levels of Atg13, LC3 and p62. Oligonol restored mitochondrial dynamics and biogenesis, which contribute to the inhibiting autophagy evidenced in SAMP8. In conclusions, our results suggest oligonol as a supplement for alleviating sarcopenia evidenced by improving protein synthesis via PI3K/AKT pathway, suppressing protein degradation via ubiquitin-proteasome system, autophagy-lysosome system, mitochondrial dynamics and biogenesis and reducing inflammatory mediators in SAMP8.

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