Nugara Ruwani N, Inafuku Masashi, Takara Kensaku, Iwasaki Hironori, Oku Hirosuke
United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima, Japan; Center of Molecular Biosciences, Tropical Biosphere Research Center, University of the Ryukyus, Okinawa, Japan.
Center of Molecular Biosciences, Tropical Biosphere Research Center, University of the Ryukyus, Okinawa, Japan.
Nutrition. 2014 Oct;30(10):1177-84. doi: 10.1016/j.nut.2014.01.015. Epub 2014 Feb 15.
Partially purified hexane phase (HP) of Peucedanum japonicum Thunb (PJT) was identified as an antiobesity candidate. However, the compound responsible for the antiobesity activity remained unknown. Thus, in this study we isolated the active compound, to determine the mechanisms related to antiobesity activity in vitro.
The HP was fractionated, and the effect on the triacylglycerol (TG) content was evaluated in 3T3-L1 preadipocytes and HepG2 hepatocytes. On the basis of comprehensive spectroscopic analyses, the structure of the active compound was identified as pteryxin, a known compound in PJT. However, to our knowledge, its biological activities against obesity have not been reported previously. The dose-dependent effect on the TG content, and the gene expressions related to adipogenesis, fatty acid catabolism, energy expenditure, lipolysis, and lipogenesis due to pteryxin (10, 15, and 20 μg/mL) were examined in vitro.
Pteryxin dose dependently suppressed TG content in both 3T3-L1 adipocytes (by 52.7%, 53.8%, and 57.4%, respectively; P < 0.05) and HepG2 hepatocytes (by 25.2%, 34.1%, and 27.4%, respectively; P < 0.05). Sterol regulatory element-binding protein-1 (SREBP-1c), fatty acid synthase (FASN), and acetyl-coenzyme A carboxylase-1 (ACC1) were down-regulated in pteryxin-treated 3T3-L1 adipocytes (by 18%, 36.1%, and 38.2%, P < 0.05) and HepG2 hepatocytes (by 72.3%, 62.9%, and 38.8%, respectively; P < 0.05). The adipocyte size marker gene, paternally expressed gene1/mesoderm specific transcript (MEST) was down-regulated (by 42.8%; P < 0.05), and hormone-sensitive lipase, a lipid catabolizing gene was up-regulated (by 15.1%; P < 0.05) in pteryxin-treated adipocytes. The uncoupling protein 2 (by 77.5%; P < 0.05) and adiponectin (by 76.3%; P > 0.05) were up-regulated due to pteryxin.
Our study demonstrated that pteryxin in PJT plays the key role in regulating the lipid metabolism-related gene network and improving energy production in vitro. Thus, the results suggest pteryxin as a new natural compound to be used as an antiobesity drug in the pharmaceutical industry.
日本前胡（Peucedanum japonicum Thunb，PJT）的部分纯化己烷相（HP）被确定为一种抗肥胖候选物。然而，负责抗肥胖活性的化合物仍不清楚。因此，在本研究中，我们分离出活性化合物，以确定体外抗肥胖活性相关的机制。
对HP进行分级分离，并在3T3-L1前脂肪细胞和HepG2肝细胞中评估其对三酰甘油（TG）含量的影响。基于综合光谱分析，活性化合物的结构被鉴定为pteryxin，这是PJT中的一种已知化合物。然而，据我们所知，其对肥胖的生物学活性此前尚未见报道。在体外检测了pteryxin（10、15和20μg/mL）对TG含量的剂量依赖性影响，以及与脂肪生成、脂肪酸分解代谢、能量消耗、脂肪分解和脂肪生成相关的基因表达。
pteryxin剂量依赖性地抑制3T3-L1脂肪细胞（分别降低52.7%、53.8%和57.4%；P<0.05）和HepG2肝细胞（分别降低25.2%、34.1%和27.4%；P<0.05）中的TG含量。在pteryxin处理的3T3-L1脂肪细胞（分别降低18%、36.1%和38.2%，P<0.05）和HepG2肝细胞（分别降低72.3%、62.9%和38.8%；P<0.05）中，固醇调节元件结合蛋白-1（SREBP-1c）、脂肪酸合酶（FASN）和乙酰辅酶A羧化酶-1（ACC1）下调。脂肪细胞大小标记基因父源表达基因1/中胚层特异性转录本（MEST）在pteryxin处理的脂肪细胞中下调（降低42.8%；P<0.05），而脂质分解代谢基因激素敏感性脂肪酶上调（升高15.1%；P<0.05）。由于pteryxin，解偶联蛋白2（升高77.5%；P<0.05）和脂联素（升高76.3%；P>0.05）上调。
我们的研究表明，PJT中的pteryxin在体外调节脂质代谢相关基因网络和改善能量产生中起关键作用。因此，结果表明pteryxin是一种新的天然化合物，可在制药行业用作抗肥胖药物。
