Merging bioactivity with liquid chromatography-mass spectrometry-based chemometrics to identify minor immunomodulatory compounds from a Micronesian adaptogen, Phaleria nisidai
Merging bioactivity with liquid chromatography-mass spectrometry-based chemometrics to identify minor immunomodulatory compounds from a Micronesian adaptogen, Phaleria nisidai
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DOI：
10.1016/j.chroma.2014.08.049
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发表时间：
2014-10-17
影响因子：
4.1
通讯作者：
Kennelly, Edward J.
中科院分区：
文献类型：
--
作者：
Kulakowski, Daniel M.;Wu, Shi-Biao;Kennelly, Edward J.
这项研究提出了一种策略，基于可重复的反相LC-TOF-MS方法和化学计量统计工具，包括非靶标PCA和监督的OPLS-DA模型，以确定在密克罗尼西亚帕劳群岛上作为适应原使用的一种植物Phaleria nisidai(Thymelaeaceae)中具有强大免疫刺激活性的低产化合物。在LC-TOF-MS化学计量学分析之前，使用干扰素-伽马-ELISA法根据免疫调节活性对色谱组分进行分类，以确定可能对观察到的活性有贡献的化合物。单纯素是一种瑞香烷二萜酯类化合物，为首次从该属植物中分离得到，可引起外周血单核细胞分泌细胞因子(干扰素-γ、白介素1-β、白介素6和白介素13)的增加。根据质谱学数据，首次从该植物中初步鉴定了另外5个瑞香烷二萜酯类化合物，它们是区分活性和非活性部位的标志性代谢物。这种分析方法提高了生物活性导向分离的效率，并有可能最大限度地减少多余的分离，并从复杂的基质中鉴定具有强大活性的次要成分。(C)2014爱思唯尔B.V.保留所有权利。
This study presents a strategy based on repeatable reversed-phase LC-TOF-MS methods and chemometric statistical tools, including untargeted PCA and supervised OPLS-DA models, to identify low-yielding compounds with potent immunostimulant activity in Phaleria nisidai (Thymelaeaceae), a plant with a history of use as an adaptogen on the islands of Palau in Micronesia. IFN gamma ELISA assays were used to classify chromatographic fractions according to imunomodulatory activity prior to LC-TOF-MS chemometric analysis to target and identify compounds likely to contribute to observed activity. Simplexin, a daphnane diterpene ester, was identified for the first time from this genus and caused an increase in the production of cytokines (IFN gamma, IL1 beta, IL6, and IL13) by peripheral blood mononuclear cells. Five other daphnane diterpene esters were tentatively identified for the first time from this plant based on mass spectral data and are marker metabolites distinguishing active from inactive fractions. This analytical approach increased the efficiency of bioactivity-guided fractionation and has the potential to minimize redundant isolation and identify minor constituents with potent activity from a complex matrix. (C) 2014 Elsevier B.V. All rights reserved.