title: Enhancing bio-availability of β-naphthoflavone by supramolecular complexation with 6,6'-thiobis(methylene)-β-cyclodextrin dimer.
abstract: The aryl hydrocarbon receptor (AhR) is a ligand activated transcriptional regulator, which governs key biological processes including detoxification of carcinogens. β-Naphthoflavone (β-NF) is a non-toxic flavonoid, and a potent AhR agonist. Thus, β-NF can induce the representative detoxifying enzyme cytochrome P4501A1, thereby enhancing the detoxification potential. However, its low water solubility hampers the use. We found that supramolecular complexation of β-NF with the synthetic 6,6'-thiobis(methylene)-β-cyclodextrin (β-CD-S) dimer significantly enhanced β-NF's role as an AhR agonist. The water solubility of β-NF was increased to 469 fold by effective supramolecular complexation with the β-CD-S dimer, and caused significant induction of cytochrome P4501A1. Stable formation of the supramolecular complex of β-NF with β-CD-S-dimer was verified by various analyses. In summary, supramolecular complexation of β-NF with β-CD-S dimer greatly enhanced bio-availability of β-NF as an AhR agonist. Our findings provide an easy, non-destructive, and alternative approach to enhance the bio-availability of therapeutics.
authors.affiliation: Center for Biotechnology Research in UBITA (CBRU), Institute for Ubiquitous Information Technology and Applications (UBITA), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Electronic address: jm.choi.25@gmail.com.
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Choi
authors.affiliation: Center for Biotechnology Research in UBITA (CBRU), Institute for Ubiquitous Information Technology and Applications (UBITA), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Electronic address: 82goodgirl@hanmail.net.
authors.forename: Eunae
authors.initials: E
authors.lastname: Cho
authors.affiliation: Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MBRC) & Center for Biotechnology Research in UBITA (CBRU), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Electronic address: formangel@naver.com.
authors.forename: Benel
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MBRC) & Center for Biotechnology Research in UBITA (CBRU), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Electronic address: darkamir@nate.com.
authors.forename: Daham
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Departments of Food Science and Technology, BioChip Research Center, Hoseo University, 20, Hoseo-ro 79 beon-gil, Baebang-eup, Asan-si 31499, Chungcheongnam-do, Republic of Korea. Electronic address: ojchoi@hoseo.edu.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Departments of Bacteriology and Genetics, University of Wisconsin, Madison 53706, WI, USA. Electronic address: jyu1@wisc.edu.
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Yu
authors.affiliation: Department of Bioscience and Biotechnology, Microbial Carbohydrate Resource Bank (MBRC) & Center for Biotechnology Research in UBITA (CBRU), Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Electronic address: shjung@konkuk.ac.kr.
authors.forename: Seunho
authors.initials: S
authors.lastname: Jung
mesh_terms: D001682:Biological Availability; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D012995:Solubility; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018336:Receptors, Aryl Hydrocarbon; D047392:beta-Cyclodextrins; D019324:beta-Naphthoflavone; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1
keywords: 6,6′-thiobis(methylene)-β-cyclodextrin dimer; Aryl hydrocarbon receptor agonist; Complexation; Solubilization; β-Naphthoflavone