Chapter 4 - Drug Metabolism and Pharmacokinetic Diversity of Ranunculaceae Medicinal Compounds

Abstract

Chemical components of the Ranunculaceae family include several representative groups: benzylisoquinoline alkaloid, ranunculin, triterpenoid saponin, diterpene alkaloid, etc. 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 Ranunculaceae-derived medicinal compounds have not been summarized. Black cohosh (Cimicifuga) and goldenseal (Hydrastis) raise concerns of herb-drug interaction. DMPK studies of other Ranunculaceae genera, for example, Nigella, Delphinium, Aconitum, Trollius, and Coptis, are also rapidly increasing and becoming more and more clinically relevant. In this chapter, 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, is highlighted. 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 the TCM formula. Although progress has been made on revealing the absorption, distribution, metabolism, excretion, and toxicity of Ranunculaceae compounds, there is a lack of DMPK studies of the 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 interindividual inconsistency of drug metabolism.