Emerging applications of metabolomics in studying chemopreventive phytochemicals

Abstract

Phytochemicals from diet and herbal medicines are under intensive investigation for their potential use as chemopreventive agents to block and suppress carcinogenesis. Chemical diversity of phytochemicals, together with complex metabolic interactions between phytochemicals and biological system, can overwhelm the capacity of traditional analytical platforms, and thus pose major challenges in studying chemopreventive phytochemicals. Recent progresses in metabolomics have transformed it to become a robust systems biology tool, suitable for examining both chemical and biochemical events that contribute to the cancer prevention activities of plant preparations or their bioactive components. This review aims to discuss the technical platform of metabolomics and its existing and potential applications in chemoprevention research, including identifying bioactive phytochemicals in plant extracts, monitoring phytochemical exposure in humans, elucidating biotransformation pathways of phytochemicals, and characterizing the effects of phytochemicals on endogenous metabolism and cancer metabolism.

Fig. 1

The work flow of untargeted metabolomics. Samples from diverse sources need to be processed appropriately to make them compatible with MS- and NMR-based metabolomic analysis. Chemical derivatization can be performed to facilitate the chromatographic separation of metabolites and increase the sensitivity of metabolite detection in LC-MS and GC-MS systems. Spectral data acquired by MS and NMR need to be deconvoluted to a data matrix compatible to multivariate data analysis. Subsequently, a multivariate model can be established in which the scores plot illustrates the principal or latent components of the model as well as sample classification while the loadings plot presents the contribution of each ion to sample classification in the model

Fig. 2

Major applications of metabolomics in studying chemopreventive phytochemicals in vitro and in vivo. Metabolomics-based phytochemical profiling and in vitro bioassays of chemopreventive activities may establish the correlation between specific phytochemicals in plant extracts and different bioactivity of plant preparations, leading to the identification of bioactive phytochemicals. Depending on the experimental design, metabolomic analysis of biological samples from the treatments of phytochemicals or plant extracts can be utilized to evaluate phytochemical exposure, elucidate biotransformation pathways of phytochemicals, and characterize the effects of phytochemicals on endogenous metabolism and cancer metabolism

Fig. 3

Utilization of metabolomics in both exploratory and hypothesis-driven investigation of phytochemical-related metabolic events. Metabolic events in phytochemical treatment include phytochemical biotransformation and phytochemical-induced metabolic changes. Metabolomics is not only able to identify the metabolites generated or affected by these events (exploratory investigation), but also capable of revealing the mechanisms underlying these events when combined with other experimental models and biochemical analyses on upstream/downstream metabolic reactions and regulatory pathways (hypothesis-driven investigation)