香瓜茄葉萃取物對於代謝症候群及肝臟脂毒性之影響

高熱量飲食習慣與久坐不動的生活習慣引起肥胖、高血糖、高血脂及胰島素阻抗的代謝系統異常，代謝症候群為現代社會重要的全球健康議題。持續的高血脂及脂質代謝異常造成脂質清除不易而累積於肝臟中，由於肝臟為脂質代謝重要器官，脂質異常累積將引發脂毒性影響肝臟正常運作甚至造成非酒精性脂肪肝病(non-alcoholic liver disease , NAFLD)。香瓜茄葉取自香瓜茄 (Solanum muricatum Aiton)，先前研究發現香瓜茄葉水萃物(aqueous extract pepino leaves, AEPL) 能保護酒精性引起的肝損傷並且抑制酒精性脂肪肝的形成，推測AEPL具有潛力改善代謝症候群及脂質代謝異常造成的肝損傷。本研究首先建立代謝症候群動物模型，給予AEPL觀察胰島素阻抗、血脂、血糖的變化及脂質累積於肝臟的情形，並且以肝細胞探討相關分子機轉，同時以高解析液相層析串聯質譜儀(HPLC-ESI-MS/MS)方法對AEPL進行成分分析。結果發現AEPL能夠改善胰島素阻抗、降低血脂及空腹血糖值。脂質堆積於肝臟的情形在給予AEPL組別有明顯的改善，可能與AMPK(5' AMP-activated protein kinase)及SREBP-1、2(sterol regulatory element-binding proteins)調控的脂質合成途徑及PPARα(peroxisome proliferator-activated receptor α)調控的脂質氧化作用有關。在醣類代謝的部分發現AEPL透過減少肝醣分解，降低空腹血糖。除此之外，給予AEPL的代謝症候群小鼠之肝臟之抗氧化酵素活性增加。進一步以HepG2細胞分析機轉發現AEPL具有降低棕櫚酸(palmitic acid, PA)引起脂毒性之內質網壓力、維持粒線體穩定及抑制細胞凋亡發生，並且驅動Nrf2(nuclear factor erythroid 2-related factor 2)進入細胞核中促進抗氧化基因表現。成分分析結果顯示AEPL主要含有類黃酮kaempferol及isorhamentin之衍生物，兩者皆有文獻指出在脂質代謝的調控及抗氧化活性。綜合上述研究結果，AEPL具有改善代謝症候群，防止脂肪肝形成，並且保護脂毒性引起的肝損傷。本研究關於AEPL的研究可提供作為輔助治療代謝症候群及防止非酒精性脂肪肝形成的新型保健食品。

關鍵字

香瓜茄葉水萃物；代謝症候群；非酒精性脂肪肝；脂毒性；類黃酮

並列摘要

Since the accessibility of calorie-rich foods and a sedentary lifestyle causes metabolic disorders including obesity, hyperglycemia, hyperlipidemia, and insulin resistance, metabolic syndrome becomes a critical global health issue. Continuous abnormal lipid and glucose metabolism and insulin resistance elevate oxidative stress and cause lipotoxicity to liver, where is the major organ for metabolism and consequently progressing to non-alcoholic liver disease (NAFLD). Pepino leaves from pepino (Solanum muricatum Aiton) were explored that aqueous extract of pepino leaves (AEPL) ameliorated alcoholic-induced liver injuries and suppressed fatty liver formation. We suggested the potential of AEPL on preventing the progression of metabolic syndrome and alleviating lipotoxicity-induced liver injuries. The study first designed a mouse model of metabolic syndrome to investigate the effect of AEPL on insulin resistance, hyperglycemia, dyslipidemia, and lipid accumulation in liver. HepG2 cells were used to explore the further regulation of AEPL on lipotoxicity. And the compounds of AEPL were identified by HPLC-ESI-MS/MS. The results revealed that the intervention of AEPL improved insulin resistance decreased hyperlipidemia and fasting blood glucose. The lipid accumulation in liver was obviously reduced in AEPL treatment and involved with inhibiting AMPK(5' AMP-activated protein kinase) and SREBP-1and 2(sterol regulatory element-binding proteins)-mediated lipogenesis as well as promoting fatty acid oxidation through PPARα(peroxisome proliferator-activated receptor α). AEPL treatment group was observed the decline of glycogenolysis which was concerned with the reduction of fasting blood glucose. In addition, the liver antioxidant ability was elevated in AEPL group. Further molecule regulatory mechanisms were investigated by HepG2 cells and the results revealed that AEPL protected from palmitic acid (PA)-induced lipotoxicity by decreasing ER (endoplasmic reticulum) stress, preserving mitochondrial, and avoiding apoptosis cascade initiation. Also, AEPL decreased PA-induced oxidative stress by Nrf2 and antioxidant genes expressions. These bioactivities are probably related to the kaempferol and isorhamnetin derivatives. Therefore, these data demonstrated that AEPL could be a novel dietary supplement or complementary medicine for metabolic syndrome as well as NAFLD.

並列關鍵字

aqueous extract of pepino leaves ； metabolic syndrome ； NAFLD ； lipotoxicity ； flavonoids

參考文獻

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