Jung Hyun Ah, Jung Hee Jin, Jeong Hyun Young, Kwon Hyun Ju, Kim Min-Sun, Choi Jae Sue
Department of Food Science and Human Nutrition, Chonbuk National University, Jeonju, 561-756, Republic of Korea.
Arch Pharm Res. 2014 Jun;37(6):713-20. doi: 10.1007/s12272-013-0237-9. Epub 2013 Sep 8.
Fucosterol is a sterol metabolite of brown algae and regulates genes involved with cholesterol homeostasis. As a part of our continuous search for anti-obesity agents from natural marine sources, the anti-adipogenic activities of Ecklonia stolonifera and its sterol, fucosterol, were evaluated for the inhibition of adipocyte differentiation and lipid formation. Oil Red O staining was used to evaluate triglyceride contents in 3T3-L1 pre-adipocytes primed by differentiation medium (DM) I and DM II. The methanolic extract of E. stolonifera showed strong anti-adipogenic activity, and was thus fractionated with several solvents. Among the tested fractions, the dichloromethane (CH2Cl2) fraction was found to be the most active fraction, with significant inhibition (40.5 %) of intracellular lipid accumulation at a non-toxic concentration, followed by the ethyl acetate fraction (30.2 %) at the same concentration, while the n-butanol and water fractions did not show inhibitory activity within the tested concentrations. The strong anti-adipogenic CH2Cl2-soluble fraction was further purified by a repeated chromatography to yield fucosterol. Fucosterol reduced lipid contents in a concentration-dependent manner without showing any cytotoxicity. Fucosterol treatment also yielded a decrease in the expression of the adipocyte marker proteins peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα) in a concentration-dependent manner. Taken together, these results suggest that fucosterol inhibits expression of PPARγ and C/EBPα, resulting in a decrease of lipid accumulation in 3T3-L1 pre-adipocytes, indicating that the potential use of E. stolonifera and its bioactive fucosterol as an anti-obesity agent.
岩藻甾醇是褐藻的一种甾醇代谢产物,可调节与胆固醇稳态相关的基因。作为我们从天然海洋来源持续寻找抗肥胖药物的一部分,对长囊水云及其甾醇岩藻甾醇的抗脂肪生成活性进行了评估,以抑制脂肪细胞分化和脂质形成。采用油红O染色法评估经分化培养基I和分化培养基II诱导的3T3-L1前脂肪细胞中的甘油三酯含量。长囊水云的甲醇提取物显示出很强的抗脂肪生成活性,因此用几种溶剂进行了分离。在测试的馏分中,发现二氯甲烷(CH2Cl2)馏分活性最强,在无毒浓度下对细胞内脂质积累有显著抑制作用(40.5%),其次是相同浓度下的乙酸乙酯馏分(30.2%),而正丁醇和水馏分在测试浓度范围内未显示抑制活性。通过反复色谱法进一步纯化具有强抗脂肪生成活性的二氯甲烷可溶馏分,得到岩藻甾醇。岩藻甾醇以浓度依赖的方式降低脂质含量,且未显示任何细胞毒性。岩藻甾醇处理还以浓度依赖的方式使脂肪细胞标记蛋白过氧化物酶体增殖物激活受体γ(PPARγ)和CCAAT/增强子结合蛋白α(C/EBPα)的表达降低。综上所述,这些结果表明岩藻甾醇抑制PPARγ和C/EBPα的表达,导致3T3-L1前脂肪细胞中脂质积累减少,表明长囊水云及其生物活性岩藻甾醇具有作为抗肥胖药物的潜在用途。