School of Biology, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, Thailand.
J Ethnopharmacol. 2010 Jul 20;130(2):315-9. doi: 10.1016/j.jep.2010.05.010. Epub 2010 May 19.
Phyllanthus urinaria is widely used as anti-inflammatory, anti-diarrheal and hepatoprotective medicines in Asian countries such as India, China and Thailand. In Thailand, Phyllanthus urinaria is traditionally used as an adjuvant or alternative medicine for cancer patients, including liver cancer. However, there is limited scientific evidence supporting its use in cancer particularly hepatocellular carcinoma.
To investigate the cytotoxic effect of Phyllanthus urinaria extract on human hepatocellular carcinoma HepG2 cells and the effect on oxidative phosphorylation by isolated rat liver mitochondria.
HepG2 cells and isolated rat liver mitochondria were treated with the 50% methanolic extract of Phyllanthus urinaria. Cytotoxicity of the extract was assessed by trypan blue exclusion and MTT assay. Rates of oxygen consumption of isolated mitochondria were determined with a Clark oxygen electrode.
It was found that the hydromethanolic extract induced cell death of HepG2 cells in a dose-dependent fashion. The IC(50) of Phyllanthus urinaria extract measured by trypan blue exclusion and MTT assay were 431+/-65 microg/ml and 445+/-62 microg/ml, respectively. Morphological changes of the cells were also observed. With isolated rat liver mitochondria, the extract slightly stimulated mitochondrial state 4 respiration but profoundly depressed state 3 respiration and respiratory control ratio.
The extract impairs energy metabolism by acting as inhibitor of oxidative phosphorylation and weak mitochondrial uncoupler. These mitochondrial effects may play a role in the cytotoxic action of Phyllanthus urinaria extract on HepG2 cells. These results provide preliminary experimental evidence supporting the use of Phyllanthus urinaria against hepatocellular carcinoma and open the possibility of considering this plant an adjunctive medicine for the treatment of this deadly disease.
在印度、中国和泰国等亚洲国家，叶下珠被广泛用作抗炎、止泻和保肝药物。在泰国，叶下珠传统上被用作癌症患者的辅助药物或替代药物，包括肝癌。然而，目前仅有有限的科学证据支持其在癌症特别是肝细胞癌中的应用。
研究叶下珠提取物对人肝癌 HepG2 细胞的细胞毒性作用及其对分离大鼠肝线粒体氧化磷酸化的影响。
用叶下珠的 50%甲醇提取物处理 HepG2 细胞和分离的大鼠肝线粒体。用台盼蓝排斥和 MTT 测定法评估提取物的细胞毒性。用克拉克氧电极测定分离线粒体的耗氧量。
发现水-甲醇提取物以剂量依赖的方式诱导 HepG2 细胞死亡。用台盼蓝排斥和 MTT 测定法测定的叶下珠提取物的 IC50 分别为 431+/-65μg/ml 和 445+/-62μg/ml。还观察到细胞的形态变化。用分离的大鼠肝线粒体，提取物轻微刺激线粒体状态 4 呼吸，但显著抑制状态 3 呼吸和呼吸控制比。
提取物通过作为氧化磷酸化抑制剂和弱线粒体解偶联剂来损害能量代谢。这些线粒体效应可能在叶下珠提取物对 HepG2 细胞的细胞毒性作用中起作用。这些结果提供了初步的实验证据，支持将叶下珠用于治疗肝细胞癌，并为将这种植物作为治疗这种致命疾病的辅助药物提供了可能性。
