Pharmacokinetic and Metabolic Profiling of Key Active Components of Dietary SupplementExtract for Prevention against Oral Carcinoma.
J Agric Food Chem. 2020 Jun 17 ;68(24):6576-6587. Epub 2020 Jun 4. PMID: 32348135
Among the three key active components (KACs) ofbark extract (ME), 4--methylhonokiol and honokiol showed higher antiproliferation activities than magnolol in the oral squamous cancer cell lines (Cal-27, SCC-9, and SCC-4). Oral bioavailabilities of ME-KACs were poor (<0.2%) in C57BL/6 mice primarily due to their extensive first-pass phase II metabolism and poor solubilities. High plasma concentration of glucuronides upon oral administration and faster rate of glucuronidation by intestinal microsomes indicated intestine as one of the major metabolic organs for ME-KACs. Despite the increase in bioavailabilities of ME-KACs (∼8-10-fold) and decrease in AUCof glucuronides (∼10-fold) upon ME solubility enhancement, systemic exposure of ME-KACs failed to improve meaningfully. In conclusion, we propose a quality-controlled and chemically defined ME mixture, containing an optimized ratio of three KACs, delivered locally in the oral cavity as the most promising strategyfor ME use as an oral cancer chemopreventive dietary supplement.