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口服琥珀酸二乙酯 DWP208 可改善 ZYM201 的琥珀酸钠形式引起的酒精性高脂血症。

Alcohol-induced Hyperlipidemia Is Ameliorated by Orally Administered DWP208, a Sodium Succinate Form of ZYM201.

机构信息

Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Korea.

College of Pharmacy, Kyungsung University, Busan 608-736, Korea.

出版信息

Korean J Physiol Pharmacol. 2014 Dec;18(6):469-74. doi: 10.4196/kjpp.2014.18.6.469. Epub 2014 Dec 30.

DOI:10.4196/kjpp.2014.18.6.469
PMID:25598660
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4296035/
Abstract

DWP208 is a sodium succinate form of ZYM-201 which is a triterpenoid glycoside isolated from Sanguisorba officinalis, a medicinal plant prescribed for various diseases, such as duodenal ulcers and bleeding in East Asian counties. We demonstrated that this compound is able to normalize the altered lipid metabolism induced by hyperglycemia and a high fat diet. In this study, we determined whether hyperlipidemic conditions induced with chronically treated alcohol can also be restored by DWP208. Similar to our previous results, orally administered DWP208 (1 to 10 mg/kg) also ameliorated the hyperlipidemia that was induced by alcohol. This compound reversed the alcohol-induced hyperlipidemia including (i) up-regulated hyperlipidemic parameters such as low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), atherosclerotic index (AI), triglyceride, and total cholesterol, and (ii) down-regulated hyperlipidemic parameters such as absolute body weight, superoxide dismutase (SOD) activity, and high-density lipoprotein (HDL) in serum and liver. According to our data, the ameliorative activity of DWP208 is due to its indirect anti-oxidative activity as a result of which lipid peroxide and hydroxyl radical levels were reduced and the activity of SOD was enhanced. Therefore, our data strongly suggest that DWP208 can be used as a remedy against alcohol-induced hyperlipidemia.

摘要

DWP208 是 ZYM-201 的琥珀酸盐形式,ZYM-201 是一种从药用植物地榆中分离得到的三萜糖苷,用于治疗多种疾病,如十二指肠溃疡和东亚国家的出血。我们证明,这种化合物能够使高血糖和高脂肪饮食引起的脂质代谢异常恢复正常。在这项研究中,我们确定了慢性酒精处理引起的高脂血症是否也可以被 DWP208 恢复。与我们之前的结果类似,口服给予 DWP208(1 至 10mg/kg)也可改善酒精引起的高脂血症。该化合物逆转了酒精引起的高脂血症,包括:(i)上调了高脂血症参数,如低密度脂蛋白(LDL)、极低密度脂蛋白(VLDL)、动脉粥样硬化指数(AI)、甘油三酯和总胆固醇;(ii)下调了高脂血症参数,如血清和肝脏中的体重、超氧化物歧化酶(SOD)活性和高密度脂蛋白(HDL)。根据我们的数据,DWP208 的改善作用是由于其间接的抗氧化活性,从而降低了脂质过氧化物和羟自由基的水平,并增强了 SOD 的活性。因此,我们的数据强烈表明,DWP208 可用于治疗酒精引起的高脂血症。

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本文引用的文献

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Planta Med. 2012 Jan;78(1):12-7. doi: 10.1055/s-0031-1280219. Epub 2011 Sep 16.
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Gypenosides protects dopaminergic neurons in primary culture against MPP(+)-induced oxidative injury.绞股蓝总苷可减少 MPP(+)诱导的原代培养多巴胺能神经元氧化损伤。
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Chronic alcohol consumption disrupted cholesterol homeostasis in rats: down-regulation of low-density lipoprotein receptor and enhancement of cholesterol biosynthesis pathway in the liver.慢性酒精摄入破坏了大鼠的胆固醇稳态:肝脏中低密度脂蛋白受体下调和胆固醇生物合成途径增强。
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