Open AccessPharmacokinetic and Metabolic Profiling of Key Active Components of Dietary Supplement Magnolia officinalis Extract for Prevention against Oral Carcinoma
Author(s) -
Dinh Bui,
Li Li,
Tongming Yin,
Xinli Wang,
Song Gao,
Ming You,
Rashim Singh,
Ming Hu
Publication year - 2020
Publication title -
journal of agricultural and food chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.203
H-Index - 297
eISSN - 1520-5118
pISSN - 0021-8561
DOI - 10.1021/acs.jafc.0c01475
Subject(s) - honokiol , magnolia officinalis , magnolol , bioavailability , pharmacokinetics , oral administration , pharmacology , chemistry , glucuronidation , kampo , first pass effect , metabolism , medicine , biochemistry , microsome , traditional chinese medicine , enzyme , alternative medicine , pathology
Among the three key active components (KACs) of Magnolia officinalis bark extract (ME), 4- O -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 AUC 0-24 of 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 strategy for ME use as an oral cancer chemopreventive dietary supplement.