title: Plasma Pharmacokinetics of Polyphenols in a Traditional Japanese Medicine, Jumihaidokuto, Which Suppresses Propionibacterium acnes-Induced Dermatitis in Rats.
abstract: Most orally administered polyphenols are metabolized, with very little absorbed as aglycones and/or unchanged forms. Metabolic and pharmacokinetic studies are therefore necessary to understand the pharmacological mechanisms of polyphenols. Jumihaidokuto (JHT), a traditional Japanese medicine, has been used for treatment of skin diseases including inflammatory acne. Because JHT contains various types of bioactive polyphenols, our aim was to clarify the metabolism and pharmacokinetics of the polyphenols in JHT and identify active metabolites contributing to its antidermatitis effects. Orally administered JHT inhibited the increase in ear thickness in rats induced by intradermal injection of Propionibacterium acnes. Quantification by LC-MS/MS indicated that JHT contains various types of flavonoids and is also rich in hydrolysable tannins, such as 1,2,3,4,6-penta-O-galloyl glucose. Pharmacokinetic and antioxidant analyses showed that some flavonoid conjugates, such as genistein 7-O-glucuronide and liquiritigenin 7-O-glucuronide, appeared in rat plasma and had an activity to inhibit hydrogen peroxide-dependent oxidation. Furthermore, 4-O-methylgallic acid, a metabolite of Gallic acid, appeared in rat plasma and inhibited the nitric oxide reaction. JHT has numerous polyphenols; it inhibited dermatitis probably via the antioxidant effect of its metabolites. Our study is beneficial for understanding in vivo actions of orally administered polyphenol drugs.
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. matsumoto_takashi@mail.tsumura.co.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. matsubara_yousuke@mail.tsumura.co.jp.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Matsubara
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. mizuhara_yasuharu@mail.tsumura.co.jp.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Mizuhara
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. sekiguchi_kyouji@mail.tsumura.co.jp.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Sekiguchi
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. koseki_junichi@mail.tsumura.co.jp.
authors.forename: Junichi
authors.initials: J
authors.lastname: Koseki
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. tsuchiya_kazuaki@mail.tsumura.co.jp.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Tsuchiya
authors.affiliation: Kampo Formulations Development Center, Production Division, Tsumura & Co., Ibaraki 300-1192, Japan. nishimura_hiroaki@mail.tsumura.co.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nishimura
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. watanabe_junko@mail.tsumura.co.jp.
authors.forename: Junko
authors.initials: J
authors.lastname: Watanabe
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. kaneko_atsushi@mail.tsumura.co.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kaneko
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. maemura_kazuya@mail.tsumura.co.jp.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Maemura
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. hattori_tomohisa@mail.tsumura.co.jp.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki 300-1192, Japan. kase_yoshio@mail.tsumura.co.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000975:Antioxidants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003872:Dermatitis / Q000188:drug therapy* / Q000382:microbiology; D044950:Flavanones / Q000097:blood / Q000493:pharmacokinetics; D019833:Genistein / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008519:Medicine, Traditional; D010936:Plant Extracts / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D059808:Polyphenols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011425:Propionibacterium acnes / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D044950:Flavanones; D010936:Plant Extracts; D059808:Polyphenols; C466949:jumi-haidoku-to; D019833:Genistein; C083152:liquiritigenin
keywords: Gallic acid; antioxidant; dermatitis; flavonoid; genistein; glucuronides; jumihaidokuto; liquiritigenin; pharmacokinetics; tannin