Cancer Chemoprevention with Korean Angelica: Active Compounds, Pharmacokinetics, and Human Translational Considerations.

Angelica gigas Nakai (AGN) is a major medicinal herb used in Korea and several other Asian countries. Traditionally, its dried root has been used to treat anemia, pain, infection and articular rheumatism, most often through boiling in water to prepare the dosage forms. AGN extract or AGN-containing herbal mixtures are sold in the US and globally as dietary supplements for pain killing, memory enhancement and post-menopausal symptom relief. Decursin (D) and its isomer decursinol angelate (DA) are the major chemicals in the alcoholic extracts of the root of AGN. The anti-cancer activity of AGN alcoholic extract has been established in a number of animal cancer models, including a transgenic model of prostate carcinogenesis. Cell culture structure-activity studies have uncovered distinct cellular and molecular effects of D and DA vs. their pyranocoumarin core decursinol (DOH) with respect to cancer cells and those associated with their microenvironment. Pharmacokinetic (PK) study by us and others in rodent models indicated that DOH is the major and rapid in vivo first-pass liver metabolite of D and DA. Cognizant of metabolic differences among rodents and humans, we carried out a first-in-human PK study of D/DA to inform the translational relevance of efficacy and mechanism studies with rodent models. The combined use of vigorous animal tests and human PK studies can provide stronger scientific rationale to inform design and execution of translational studies to move AGN toward evidence-based herbal medicine.