In vivo efficacy study of milk thistle extract (ETHIS-094™) in STAM™ model of nonalcoholic steatohepatitis.

In vivo efficacy study of milk thistle extract (ETHIS-094™) in STAM™ model of nonalcoholic steatohepatitis.
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DOI:
10.1007/s40268-014-0068-2
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发表时间:
2014-12
期刊:
影响因子:
3
通讯作者:
D'Amato, Massimo
D'Amato, Massimo
中科院分区:
医学4区
文献类型:
--
作者:
Pais, Pilar;D'Amato, Massimo

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非酒精性脂肪性肝炎(NASH)是非酒精性脂肪性肝病(NAFLD)的一个亚类,其特征在于脂肪积聚,伴有炎症浸润和肝细胞损伤。水飞蓟的活性复合物是其种子的亲脂性提取物,包含三种异构体,统称为水飞蓟素。水飞蓟素已被证明具有抗氧化、抗炎和抗纤维化的特性,并已被广泛研究用于治疗肝脏疾病。大多数已发表的关于水飞蓟素的临床研究都使用了Legalon®(Rottapharm/Madaus),其中含有获得专利的奶蓟提取物ETIS-094™(Euromed)。进行本研究以检查ETIS-094™在Stelic动物模型(STAM™)中的作用,Stelic动物模型(STAM™)是一种经验证且广泛使用的NASH动物模型。在4至8周龄禁食4小时后,每天一次口服施用其中已诱导NASH的15只雄性小鼠(1)体积为10 mL/kg的媒介物(盐水),(2)补充有剂量为500 mg/kg的奶蓟的媒介物,或(3)补充有剂量为1,000 mg/kg的奶蓟的媒介物。与溶剂组相比,水飞蓟高剂量组的平均肝脏重量和肝体重比显著降低(P < 0.01)。与媒介物组相比,奶蓟治疗组的NAFLD活动评分(NAS)倾向于降低,脂肪变性评分也是如此。与溶媒组相比,水飞蓟提取物给药诱导NAS降低趋势。与溶剂相比,水飞蓟诱导脂肪变性评分数值降低,并伴有肝脏重量和肝脏/体重比的统计学显著性降低,表明水飞蓟具有潜在的抗脂肪变性作用。本文的在线版本(doi:10.1007/s40268-014-0068-2)包含补充材料,可供授权用户使用。
A subcategory of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) is characterized by accumulation of fat accompanied by inflammatory infiltration and hepatocellular damage. The active complex of milk thistle is a lipophilic extract from its seeds, comprising three isomers, collectively known as silymarin. Silymarin has demonstrated antioxidant, anti-inflammatory, and antifibrotic properties, and has been extensively studied in the treatment of liver diseases. The majority of published clinical research on silymarin has used Legalon® (Rottapharm/Madaus), containing the patented extract of milk thistle ETHIS-094™ (Euromed). The current study was undertaken to examine the effects of ETHIS-094™ in the Stelic Animal Model (STAM™), a validated and widely used animal model for NASH. After 4 h fasting from 4 to 8 weeks of age, 15 male mice in whom NASH had been induced were orally administered, once daily, either (1) vehicle (saline) at a volume of 10 mL/kg, (2) vehicle supplemented with milk thistle at a dose of 500 mg/kg, or (3) vehicle supplemented with milk thistle at a dose of 1,000 mg/kg. Mean liver weight and the liver-to-body weight ratio were significantly (P < 0.01) decreased in the milk thistle high-dose group compared with the vehicle group. NAFLD activity score (NAS) tended to decrease in the milk thistle treatment groups compared with vehicle group, as did steatosis scores. Milk thistle extract administration induced a decreasing trend in NAS compared with the vehicle group. Milk thistle induced a numerical decrease of the steatosis score compared with vehicle, and this was accompanied by a statistically significant decrease in liver weight and the liver-to-body weight ratio, implying a potential anti-steatosis effect of milk thistle. The online version of this article (doi:10.1007/s40268-014-0068-2) contains supplementary material, which is available to authorized users.