Drug metabolism and disposition diversity of Ranunculales phytometabolites: a systems perspective

ABSTRACT

Introduction: Although investigations in metabolism and pharmacokinetics of Ranunculales phytometabolites are booming, data obtained from human and animal studies have not been summarized as a whole to outline current trends and to predict future development.

Areas covered: Here, we highlight the current knowledge, as well as the challenges around the DMPK (drug metabolism and pharmacokinetics) associated concerns in streamlining drug research and therapeutic use of Ranunculales phytometabolites. Data from various in vivo and in vitro models are classified and discussed. DMPK characteristics of Ranunculales phytometabolites are summarized and presented according to the phylogenetic relationship of families and genera. This review also presents an overview of the complex interaction between drug metabolizing enzymes/transporters and phytochemicals, as well as of the most advanced approaches in the relevant field.

Expert opinion: Since species-specific differences in DMPK exist, data obtained from animal studies may not be sufficient to predict drug metabolism reactions in humans. Omics-based methodologies (genomics, epigenomics, transcriptomics, proteomics, microbiomics, and metabolomics) should be used to enhance the reliability of DMPK prediction. The fluorescent probes may bridge the gap between conventional models and in vivo clinical studies in humans and provide a consistent basis for DMPK assay development.

KEYWORDS:

• Phytometabolite
• systems perspective
• Ranunculales
• drug metabolism and disposition
• diversity

Article highlights

• Summarize DMPK studies of Ranunculales phytometabolites as a whole to outline current trends and to predict future development

• Classify and discuss in vivo and in vitro data; present DMPK characteristics of Ranunculales flavonoids, saponins, and alkaloids, according to the phylogenetic relationship

• Highlight the complex interaction between DMEs/transporters and phytochemicals, especially those in TCM formula, as well as most advanced approaches in the relevant field

• Omics-based methodologies should be used to enhance the reliability of DMPK prediction

• The fluorescent probes may bridge the gap between conventional models and in vivo clinical studies and provide a consistent basis for DMPK assay development

• The early ADME/T study of TCM is a commanding device in deciphering TCM at the level of systems biology

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Declaration of interest

This work is supported by Liaoning natural science fund (2015020663). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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