黃連水萃物與酒萃物透過不同機轉影響早期脂肪細胞分化

Water and ethanol extracts of Coptidis Rhizoma affect the early stage of adipogenesis by different mechanisms

柯雅甄(Ya-Chen Ko)

指導教授 ： 王惠君

高雄醫學大學/藥學院/天然藥物研究所碩士班/碩士(2019年)

摘要

全球的肥胖人口比例逐年的升高，成為無法忽視的疾病風險。在3T3-L1脂肪細胞分化模式中，已知胰島素、糖皮質素、和3-isobuty-1-methylxanthine (IBMX)，簡稱MDI。這三種因素在誘導脂質細胞分化過程中缺一不可。藉由胰島素和cAMP分別活化PI3K/Akt和cAMP-dependent protein kinase (PKA)/ cAMP response element-binding protein (CREB)，在早期階段的脂質生成中扮演著很重要的角色，能進一步的誘導peroxisome proliferator-activated receptor γ (PPARγ) 與CCAAT-enhancer-binding protein α (C/EBPα) 的基因表現，促使脂肪細胞的產生。本實驗室過去研究發現黃連水萃物 (CRW) 及酒萃物 (CRE) 都能在脂肪細胞分化的早期有抑制的效果。因此本研究目的是要探討黃連水萃物或酒萃物在早期的脂質生成階段對於MDI誘導分化培養基所誘導的CREB和AKT磷酸化活化的影響。
結果顯示，MDI刺激3T3-L1脂肪前驅細胞30分鐘後就可以磷酸化CREB和AKT。而前處理黃連水萃物、酒萃物或黃連有效主成分小蘗鹼都顯著抑制MDI刺激所活化的CREB磷酸化，但在AKT磷酸化方面則會提升。以不同誘導分化培養液分別刺激3T3-L1脂肪細胞作用30分鐘後，黃連水萃物、酒萃物或黃連有效主成分小蘗鹼都能有效抑制由IBMX誘導的CREB磷酸化。另一方面，結果顯示CRW、CRE和BBR在胰島素所誘導的AKT磷酸化模式中，各自有著不同的作用。我們以不同因子誘發信息的方式可以將黃連萃取物的分子作用機轉一一釐清，有助於未來了解黃連不同有效成分抑制脂肪細胞分化的作用機轉。

關鍵字

黃連 ； 抗脂肪生成 ； 3T3-L1脂肪細胞 ； 肥胖

並列摘要

The incidence of obesity increasing progressively worldwide becomes an unignorable risk of many diseases. In the in vitro study model, it is known that insulin, glucocorticoids, and 3-isobutyl-1-methylxanthine (IBMX), which called MDI. They are indispensable for 3T3-L1 adipogenesis. The PI3K/AKT and cAMP-dependent protein kinase (PKA)/ cAMP response element-binding protein (CREB) respectively activated by insulin and IBMX have an important roles at the early stage of adipogenesis, which are induced peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding protein α (C/EBPα) gene expression to produce adipocytes. Previous studies from our lab found that the water (CRW) and ethanol (CRE) extracts from Coptidis rhizoma inhibited 3T3-L1 adipogenesis at the early stage. Therefore, the purpose of this study is to investigate the effects of CRW or CRE on MDI induction medium induced CREB and AKT phosphorylation during 3T3-L1 adipogenesis at the early stage. Our results show that the CREB and AKT phosphorylation are soon induced by MDI stimulation for 30 mins in 3T3-L1 pre-adipocytes. The CREB phosphorylation is inhibited by pre-treatment of CRW, CRE and the major constituent of Coptidis rhizoma berberine (BBR), but AKT phosphorylation is increased. By different induction medium stimulated CREB or AKT phosphorylation on 3T3-L1 adipocytes for 30 mins, CRW, CRE, and BBR are significantly inhibited CREB phosphorylation on IBMX induction medium model. On the other hand, the data show CRW, CRE, and BBR have a different effect on the insulin induction medium model. In this way, applying differentiation inducers individually we could clarify the mechanism of action for the compounds in Coptidis rhizoma extracts on against 3T3-L1 adipogenesis.

並列關鍵字

Coptidis rhizoma ； anti-adipogenic ； 3T3-L1 adipocyte ； obesity

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