基因表达谱分析揭示了叶下珠对硫代乙酰胺诱导的 Sprague Dawley 大鼠肝毒性的保护作用的潜在分子机制。
Gene expression profiling reveals underlying molecular mechanism of hepatoprotective effect of Phyllanthus niruri on thioacetamide-induced hepatotoxicity in Sprague Dawley rats.
出版信息
BMC Complement Altern Med. 2013 Jul 5;13:160. doi: 10.1186/1472-6882-13-160.
BACKGROUND
The liver plays an essential role in the body by regulating several important metabolic functions. Liver injury is associated with the distortion of these functions causing many health problems. Pharmaceutical drugs treat liver disorders but cause further damage to it. Hence, herbal drugs are used worldwide and are becoming increasingly popular.
METHODS
The hepatoprotective activity of Phyllanthus niruri (PN) was evaluated against liver cirrhosis induced by thioacetamide (TAA) in male Sprague Dawley rats. Rats received intraperitoneal injections of thioacetamide (TAA, 200 mg/kg, b.w. three times weekly) for eight weeks. Daily treatments with plant extract (200 mg/kg) were administered orally for eight weeks. At the end of the study, hepatic damage was evaluated by monitoring transforming growth factor (TGFβ), collagen α1 (Collα1), matrix metalloproteinase-2 (MMP2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP1) gene expression by real-time PCR. Moreover, different chromatographic techniques including column chromatography, thin layer chromatography, and Ultra Performance Liquid Chromatography (UPLC) with Liquid Chromatography/Mass Spectrometry (LC/MS) were used to isolate the active constituents of the plant.
RESULTS
The results revealed that treatment with PN significantly reduced the effect of thioacetamide toxicity and exhibited effective hepatoprotective activity. The mechanism of the hepatoprotective effect of PN is proposed to be by normalizing ROSs. Additionally, PN treatment regulated the expression of TGFβ, Collα1, MMP2, and TIMP1 genes. In the active fraction of P. niruri, the isolated chemical constituents were 4-O-caffeoylquinic acid and quercetin 3-O-rhamnoside.
CONCLUSIONS
The results of the present study indicate that PN ethanol extracts possess hepatoprotective activity that is most likely because of the isolated chemical constituents.
背景
肝脏在体内起着至关重要的作用，调节着多种重要的代谢功能。肝损伤与这些功能的扭曲有关，导致许多健康问题。药物治疗肝脏疾病，但会对其造成进一步的损害。因此，草药在全球范围内被使用，并越来越受欢迎。
方法
评估叶下珠（PN）对硫代乙酰胺（TAA）诱导的肝硬化的肝保护活性。雄性 Sprague Dawley 大鼠腹腔注射硫代乙酰胺（TAA，200mg/kg，b.w.每周三次）8 周。每天口服给予植物提取物（200mg/kg）进行 8 周的治疗。在研究结束时，通过实时 PCR 监测转化生长因子（TGFβ）、胶原α1（Collα1）、基质金属蛋白酶-2（MMP2）和基质金属蛋白酶抑制剂-1（TIMP1）基因的表达来评估肝损伤。此外，使用不同的色谱技术，包括柱色谱、薄层色谱和超高效液相色谱（UPLC）与液相色谱/质谱（LC/MS），从植物中分离活性成分。
结果
结果表明，PN 治疗可显著降低硫代乙酰胺毒性的影响，并表现出有效的肝保护活性。PN 肝保护作用的机制被提出是通过使 ROS 正常化。此外，PN 治疗还调节了 TGFβ、Collα1、MMP2 和 TIMP1 基因的表达。在 P. niruri 的活性部分中，分离出的化学成分为 4-O-咖啡酰奎宁酸和槲皮素 3-O-鼠李糖苷。
结论
本研究结果表明，PN 乙醇提取物具有肝保护活性，这很可能是由于分离出的化学成分。
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