育碧加冬提取物与妊娠大鼠肝毒性相关的基因表达谱

Ezarul Faradianna Lokman, H. Muhammad, N. Awang, Maizatul Hasyima Omar, F. Mansor, Fatin Saparuddin
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引用次数: 5

摘要

薯蓣是马来西亚最著名的淀粉块茎,被称为“ubi gadong”。尽管担心毒性作用,但由于存在生物活性化合物,如皂苷,已知块茎具有治疗价值。本研究采用RT²Profiler PCR阵列技术,对妊娠大鼠肝毒性相关基因表达谱的变化进行了研究。采用高效液相色谱-质谱联用技术对海棘草中甾体皂苷进行了鉴定。妊娠大鼠给药剂量在2000 mg/kg b.w.以上可致死亡。PCR阵列分析结果显示,有几个基因在毒蛾处理后出现了显著的上调和下调。在2000 mg/kg b.w处理下,海丝桃Btg2、Gsr、L2hgdn、S100a8、Slc17a3、Bhmt、Cd68、Cyp1a2等基因显著上调,而Abcb1a、Aldoa、Cdc14b、Icam1、Krt18、Hpn和Maob等基因下调。以较低剂量2000 mg/kg时,对大鼠无危害。给妊娠大鼠以最高剂量给药,可引起不同肝毒性组功能基因的改变,如坏死、胆汁淤积和磷脂沉积。
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Gene Expression Profiling associated with Hepatoxicity in Pregnant Rats treated with Ubi Gadong (Dioscorea hispida) Extract
Dioscorea hispida (D.hispida) is the most well-known starchy tuber in Malaysia and called ‘ubi gadong’. Despite concerns over toxicity effects, the tuber is known to possess therapeutic values due to the presence of bioactive compounds such as saponins. This study was performed to identify the changes in gene expression profiles associated with hepatoxicity in pregnant rat treated with D.hispida using RT² Profiler PCR Array. The identification of steroidal saponins from D.hispida was carried out by UHPLC/MS method. Treatment of D.hispida caused mortality when dosage above 2000 mg/kg b.w. was given to pregnant rats. The PCR array showed that several genes were significantly up and down-regulated upon treatment with D.hispida. Treatment of D.hispida at 2000 mg/kg b.w leads to significant upregulation of several genes such as Btg2, Gsr, L2hgdn, S100a8, Slc17a3, Bhmt, Cd68, Cyp1a2 whereas several genes were downregulated such as Abcb1a, Aldoa, Cdc14b, Icam1, Krt18, Hpn and Maob. The consumption of D.hispida extract when taken at lower dosage of 2000 mg/kg may not be harmful to rats. D.hispida extract given at the highest dosage to pregnant rats caused alterations of several genes categorized in different hepatotoxic group functions such as necrosis, cholestasis and phospholipodisis.
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