title: Chemical and biological characterization and clinical evaluation of botanical dietary supplements: a phase I red clover extract as a model.
abstract: Botanical dietary supplements, as compared with nutritional supplements or single-component pharmaceutical drugs, are typically less-refined preparations derived from bulk plant material and, as such, require a modified approach to their development, production, and evaluation. An integrated, multidisciplinary team of scientific and clinical investigators is required in order to develop high quality phytomedicines and rigorously evaluate their safety and efficacy. Research on botanicals involves unique challenges as plant source materials frequently vary in chemical content and may contain unwanted pesticides, heavy metals, contaminant plant species, or other adulterants. Ideally, a botanical formulation should be standardized, both chemically and biologically, by a combination of analytical techniques and bioassays. This combination approach provides multiple measures by which reproducible quality and efficacy of botanical supplements may be achieved, and is particularly useful for botanical products for which the active compound(s) have not yet been identified. Safety and toxicity should be evaluated during the supplement development process in both in vitro and in vivo systems. A number of liquid chromatography-mass spectrometry methods can aid in the assessment of purity, bioavailability, toxicity, metabolism, and molecular target profiling of botanical extracts. Clinical investigators must appreciate the complexity of multi-component phytomedicines and adjust trial protocols accordingly. This review highlights practical considerations of value to basic science and clinical investigators engaged in the study of botanical supplements. Lessons and examples are drawn from the authors' experience in designing and developing a red clover (Trifolium pratense L.) standardized extract for evaluation in Phase I and Phase II clinical trials.
authors.affiliation: UIC/NIH Center for Botanical Dietary Supplements Research, and Department of Medicinal Cehemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Piersen
authors.forename: N L
authors.initials: NL
authors.lastname: Booth
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: W
authors.initials: W
authors.lastname: Liang
authors.forename: J E
authors.initials: JE
authors.lastname: Burdette
authors.forename: R B
authors.initials: RB
authors.lastname: van Breemen
authors.forename: S E
authors.initials: SE
authors.lastname: Geller
authors.forename: C
authors.initials: C
authors.lastname: Gu
authors.forename: S
authors.initials: S
authors.lastname: Banuvar
authors.forename: L P
authors.initials: LP
authors.lastname: Shulman
authors.forename: J L
authors.initials: JL
authors.lastname: Bolton
authors.forename: N R
authors.initials: NR
authors.lastname: Farnsworth
mesh_terms: D000818:Animals; D017321:Clinical Trials, Phase I as Topic / Q000379:methods*; D017322:Clinical Trials, Phase II as Topic; D019587:Dietary Supplements / Q000145:classification / Q000191:economics / Q000592:standards*; D004341:Drug Evaluation / Q000379:methods* / Q000639:trends; D004345:Drug Industry / Q000191:economics; D006801:Humans; D009316:National Institutes of Health (U.S.); D008517:Phytotherapy / Q000592:standards; D010936:Plant Extracts / Q000737:chemistry* / Q000191:economics / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic; D029921:Trifolium / Q000737:chemistry*; D014481:United States
chemical_list: D010936:Plant Extracts