Yimam Mesfin, Jiao Ping, Hong Mei, Jia Qi
Unigen, Inc. , Seattle, Washington, USA.
J Med Food. 2016 Aug;19(8):780-8. doi: 10.1089/jmf.2016.0023. Epub 2016 Jun 29.
Despite the promising advances in therapeutic discovery, there still is a major challenge in the development of a safe, effective, and economical intervention for managing alcohol-related liver disorders. In this study, we describe the potential use of "MAP," a standardized composition comprising three extracts from Myristica fragrans, Astragalus membranaceus, and Poria cocos, in ameliorating alcohol-induced acute liver toxicity. Ethanol-induced acute hepatotoxicity as an animal model of binge drinking was utilized. Mice received oral doses of MAP at 300 mg/kg for four consecutive days. Mice were orally gavaged with 50% ethanol in 12 mL/kg dosing volume following the third dose of MAP every 12 h thereafter for a total of three doses. Hepatic functional tests from serum collected at T12, and hepatic glutathione (GSH), superoxide dismutases (SODs), and triglyceride from liver homogenates were evaluated. Histopathology analysis and alcoholic steatohepatitis (ASH) scoring were also determined. Excessive increases of serum alanine aminotransferase and aspartate aminotransferase were significantly inhibited at 46.3% and 43.6%, respectively, when mice were treated with MAP. MAP replenished the depleted SOD by more than 60%, while causing significant stimulation of GSH productions. MAP showed statistically significant reduction in ballooning degeneration, vascular steatosis, cytoplasmic or nuclear condensation, and shrinkage, as well as inflammations when compared to vehicle-treated alcohol-induced liver toxicity model. Mice treated with MAP showed statistically significant reduction in ASH scoring when compared to vehicle control. Therefore, the composition MAP could be potentially utilized as an effective hepatic-detoxifying agent for the protection of liver damage caused by alcohol consumptions.
尽管在治疗药物研发方面取得了令人鼓舞的进展,但在开发一种安全、有效且经济的干预措施来管理酒精相关肝病方面,仍然存在重大挑战。在本研究中,我们描述了“MAP”的潜在用途,它是一种标准化组合物,由肉豆蔻、黄芪和茯苓的三种提取物组成,可改善酒精诱导的急性肝毒性。我们采用乙醇诱导的急性肝毒性作为暴饮的动物模型。小鼠连续四天口服300mg/kg的MAP。在第三次给予MAP后,每隔12小时给小鼠口服灌胃12mL/kg剂量体积的50%乙醇,共给药三次。评估在T12时采集的血清中的肝功能测试,以及肝匀浆中的肝谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和甘油三酯。还进行了组织病理学分析和酒精性脂肪性肝炎(ASH)评分。当用MAP治疗小鼠时,血清丙氨酸转氨酶和天冬氨酸转氨酶的过度升高分别被显著抑制了46.3%和43.6%。MAP使耗尽的SOD补充超过60%,同时显著刺激GSH的产生。与载体处理的酒精诱导肝毒性模型相比,MAP在气球样变性、血管脂肪变性、细胞质或核浓缩、萎缩以及炎症方面显示出统计学上的显著降低。与载体对照相比,用MAP治疗的小鼠在ASH评分上显示出统计学上的显著降低。因此,组合物MAP可能潜在地用作一种有效的肝脏解毒剂,以保护由饮酒引起的肝损伤。