| 引用本文: | 熊朝栋,陈红,陈丹,余文静,马国萍.玳玳果黄酮提取物关键效应组分辨识及调控脂质代谢作用机制研究[J].中国现代应用药学,2022,39(14):1818-1827. |
| XIONG Chaodong,CHEN Hong,CHEN Dan,YU Wenjing,MA Guoping.Study on the Identification of the Key Effect Components and the Lipid Metabolism Mechanism for Daidai Flavonoid Extracts[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(14):1818-1827. |
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| 摘要: |
| 目的 探究玳玳果黄酮提取物及其敲出目标组分对脂肪变性细胞调控脂质代谢作用及机制，辨识关键效应组分。方法 采用油酸诱导建立HepG2脂肪变性细胞模型，非诺贝特为阳性对照，油红O染色法及甘油三酯(triglycerides，TG)和总胆固醇(total cholesterol，TC)为评价指标，考察玳玳果黄酮提取物、柚皮苷(目标组分)、新橙皮苷(目标组分)、其他相关组分(黄酮提取物敲除柚皮苷、新橙皮苷)、黄酮提取物敲除其他相关组分(柚皮苷-新橙皮苷6︰ 7)对脂肪变性模型细胞脂质集聚影响。基于AMPK/SREBP-1c及PPARα信号通路，采用qRT-PCR法、Western blotting检测大鼠肝脏相关基因、蛋白的表达。结果 预防性给药后，与模型组相比，玳玳果黄酮提取物、柚皮苷、新橙皮苷、提取物敲除其他相关组分的细胞脂质积聚、TG及TC含量均有明显的改善(P<0.01或P<0.05)；玳玳果黄酮提取物及柚皮苷、新橙皮苷可使促腺苷酸激活蛋白激酶(ATP-activated protein kinase，AMPK)的mRNA及磷酸化蛋白表达水平明显升高(P<0.01或P<0.05)；显著抑制并明显下调固醇调节元件结合蛋白(sterol regulatory element binding protein，SREBP-1c)、脂肪酸合成酶(fatty acidsynthase，FAS)、乙酰辅酶羧化酶(coenzyme carboxylase，ACC)的mRNA和蛋白表达水平(P<0.01或P<0.05)；可促进过氧化物酶增殖物激活受体(peroxidase proliferator-activated receptor ，PPARα)、肉毒碱棕榈酰基转移酶(carnitinepalmitoyltransferase-1，CPT-l)的mRNA及蛋白表达水平明显上升(P<0.01或P<0.05)；其他相关组分无明显差异。结论 玳玳果黄酮提取物及其关键效应组分柚皮苷、新橙皮苷可有效改善脂质积聚；其作用机制为激活AMPK促其蛋白磷酸化表达，从而抑制脂质合成，同时促进脂肪酸的氧化分解，由此减少脂肪沉积，发挥调控脂质代谢的作用。 |
| 关键词: 玳玳果黄酮提取物 柚皮苷 新橙皮苷 HepG2细胞脂肪变性模型 促腺苷酸激活蛋白激酶 固醇调节元件结合蛋白 过氧化物酶增殖物激活受体 |
| DOI：10.13748/j.cnki.issn1007-7693.2022.14.005 |
| 分类号:R285.5 |
| 基金项目:福建省自然科学基金项目(2018J01253)；福建省卫生计生委医学创新项目(2016-CX-45)；福建省科技计划项目(2010Y2004) |
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| Study on the Identification of the Key Effect Components and the Lipid Metabolism Mechanism for Daidai Flavonoid Extracts |
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XIONG Chaodong1,2, CHEN Hong1, CHEN Dan2, YU Wenjing2, MA Guoping2
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1.Cadre Special Department, Fujian Provincial Hospital, Fuzhou 350001, China;2.Department of Pharmacy, Fujian University of TCM, Fuzhou 350122, China
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| Abstract: |
| OBJECTIVE To explore the effect and mechanism of Daidai flavonoid extracts and its key effect components on the regulation of lipid metabolism in steatosis cells and to identify the key effect components. METHODS HepG2 cell steatosis model was established by oleic acid induction. Fenofibrate was used as a positive control. The oil red O staining method, triglycerides(TG), and total cholesterol(TC) were used as evaluating indicators to investigate the effects of Daidai flavonoid extracts, naringin(key effect component), neohesperidin(key effect component), other related components(flavonoid extract excluded naringin and neohesperidin), and extracts excluded other related components(6:7 of naringin-neohesperidin) on the lipid accumulation in HepG2 cell steatosis model. Based on AMPK/SREBP-1c and PPARα signaling pathways, qRT-PCR and Western blotting were used to detect the expression of related genes and proteins in rat liver. RESULTS After preventive administration, compared with the model group, the cell lipid accumulation, TG and TC levels were significantly improved(P<0.01 or P<0.05) in the groups of Daidai flavonoid extracts, naringin, neohesperidin and extracts excluded other related components. Daidai flavonoid extracts, naringin and neohesperidin significantly increased the expression levels of ATP-activated protein kinase(AMPK) mRNA and phosphorylated protein(P<0.01 or P<0.05); inhibited and reduced the mRNA and protein expression levels of sterol regulatory element binding protein(SREBP-1c), fatty acid synthase(FAS) and acetyl coenzyme carboxylase(ACC)(P<0.01 or P<0.05); increased the mRNA and protein expression levels of peroxidase proliferator-activated receptor(PPARα) and carnitine palmitoyltransferase-1(CPT-l)(P<0.01 or P<0.05). There was no significant difference in other related component group. CONCLUSION The Daidai flavonoid extracts and the key effect components naringin and neohesperidin can effectively improve the lipid accumulation of steatosis model cells. The mechanism is to activate AMPK to promote its phosphorylation expression, thereby inhibiting lipid synthesis. At the same time, it promotes the oxidation and decomposition of fatty acids, thereby reducing fat deposition and regulating lipid metabolism. |
| Key words: Daidai flavonoid extracts naringin neohesperidin HepG2 cell steatosis model ATP-activated protein kinase(AMPK) sterol regulatory element binding protein(SREBP-1c) peroxidase proliferator activated receptor(PPARα) |
