In vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum)
In vitro cytotoxicity of nonpolar constituents from different parts of kava plant (Piper methysticum)
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DOI：
10.1021/jf051853j
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发表时间：
2006-04-19
影响因子：
6.1
通讯作者：
Ang, CYW
中科院分区：
文献类型：
--
作者：
Jhoo, JW;Freeman, JP;Ang, CYW
卡瓦胡椒（Piper methysticum）是一种原产于南太平洋岛屿的多年生灌木，已被用来缓解焦虑。最近，已经报道了几起因食用含有卡瓦的膳食补充剂而导致严重肝毒性的病例。目前尚不清楚卡瓦成分卡瓦内酯是否与相关的肝毒性有关。为了研究导致肝毒性的关键成分，本研究进行了生物测定引导的分级分离。用甲醇提取卡瓦根、叶和茎皮，并将所得残留物用不同极性的溶剂（己烷、乙酸乙酯、正丁醇和水）进行分配，以基于 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定以及乳酸脱氢酶和天冬氨酸转氨酶渗漏测定评估其对 HepG2 细胞的细胞毒性。对于卡瓦的所有部分，有机溶剂级分均表现出比水级分更强的细胞毒性。根的己烷部分比用其他溶剂提取的根部分或卡瓦其他部分的提取物表现出更强的细胞毒性作用。使用生物测定指导的己烷级分分离和分析进行的进一步研究表明，造成细胞毒性的化合物是黄卡瓦因 B。通过 H-1 和 C-13 NMR 和 MS 技术证实了该化合物的身份。
Kava (Piper methysticum), a perennial shrub native to the South Pacific islands, has been used to relieve anxiety. Recently, several cases of severe hepatotoxicity have been reported from the consumption of dietary supplements containing kava. It is unclear whether the kava constituents, kavalactones, are responsible for the associated hepatotoxicity. To investigate the key components responsible for the liver toxicity, bioassay-guided fractionation was carried out in this study. Kava roots, leaves, and stem peelings were extracted with methanol, and the resulting residues were subjected to partition with a different polarity of solvents (hexane, ethyl acetate, n-butanol, and water) for evaluation of their cytotoxicity on HepG2 cells based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and lactate dehydrogenase and aspartate aminotransferase enzyme leakage assays. Organic solvent fractions displayed a much stronger cytotoxicity than water fractions for all parts of kava. The hexane fraction of the root exhibited stronger cytotoxic effects than fractions of root extracted with other solvents or extracts from the other parts of kava. Further investigations using bioassay-directed isolation and analysis of the hexane fraction indicated that the compound responsible for the cytotoxicity was flavokavain B. The identity of the compound was confirmed by H-1 and C-13 NMR and MS techniques.