The wide-reaching distributed angiosperm family Ranunculaceae has approximately 2200 species in
around 60 genera. Chemical components of this family include several representative groups: benzylisoquinoline
alkaloid (BIA), ranunculin, triterpenoid saponin and diterpene alkaloid, etc. Their extensive clinical utility has been
validated by traditional uses of thousands of years and current evidence-based medicine studies. Drug metabolism
and pharmacokinetic (DMPK) studies of plant-based natural products are an indispensable part of comprehensive
medicinal plant exploration, which could facilitate conservation and sustainable utilization of Ranunculaceae pharmaceutical resources,
as well as new chemical entity development with improved DMPK parameters. However, DMPK characteristics of Ranunculaceaederived
medicinal compounds have not been summarized. Black cohosh (Cimicifuga) and goldenseal (Hydrastis) raise concerns of herbdrug
interaction. DMPK studies of other Ranunculaceae genera, e.g., Nigella, Delphinium, Aconitum, Trollius, and Coptis, are also rapidly
increasing and becoming more and more clinically relevant. In this contribution, we highlight the up-to-date awareness, as well as
the challenges around the DMPK-related issues in optimization of drug development and clinical practice of Ranunculaceae compounds.
Herb-herb interaction of Ranunculaceae herb-containing traditional Chinese medicine (TCM) formula could significantly influence the in
vivo pharmacokinetic behavior of compounds thereof, which may partially explain the complicated therapeutic mechanism of TCM formula.
Although progress has been made on revealing the absorption, distribution, metabolism, excretion and toxicity (ADME/T) of
Ranunculaceae compounds, there is a lack of DMPK studies of traditional medicinal genera Aquilegia, Thalictrum and Clematis. Fluorescent
probe compounds could be promising substrate, inhibitor and/or inducer in future DMPK studies of Ranunculaceae compounds.
A better understanding of the important herb-drug/herb-herb interactions, bioavailability and metabolomics aspects of Ranunculaceae
compounds will bolster future natural product-based drug design and the comprehensive investigation of inter-individual inconsistency of