title: The blood-brain barrier permeability of 18β-glycyrrhetinic acid, a major metabolite of glycyrrhizin in Glycyrrhiza root, a constituent of the traditional Japanese medicine yokukansan.
abstract: 18β-Glycyrrhetinic acid (GA) is a major metabolite of glycyrrhizin (GL), which is one of the components of glycyrrhiza root, a constituent herb of the traditional Japanese medicine yokukansan. It is well known that most GL is metabolized to GA in the intestine by bacteria. A previous in vitro study using cultured rat cortical astrocytes suggested that GA activates glutamate transport, which is a putative mechanism of the psychotropic effect of yokukansan. To activate the glutamate transport in the brain, GA must be absorbed into the blood after oral administration of yokukansan and then cross the blood-brain barrier (BBB) to reach the brain. However, there is no data on the BBB permeability of GA derived from yokukansan. In the present study, the BBB permeability of GA was investigated in both in vivo and in vitro studies. In the in vivo study, GA was detected in the plasma, brain, and cerebrospinal fluid of rats orally administered yokukansan. In the in vitro study using a BBB model composed of co-culture of endothelial cells, pericytes, and astrocytes, the permeability rate and apparent permeability coefficient of GA were found to be 13.3 ± 0.5 % and 16.5 ± 0.7 × 10(-6) cm/s. These in vivo and in vitro results suggest that GL in orally administered yokukansan is absorbed into the blood as GA, and then reaches the brain through the BBB. This evidence further supports the possibility that GA is an active component in the psychotropic effect of yokukansan.
authors.affiliation: Tsumura Research Laboratories, Tsumura & Co., Ami-machi, Inashiki-gun, Ibaraki, Japan. tabuchi_masahiro@mail.tsumura.co.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tabuchi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Imamura
authors.forename: Zenji
authors.initials: Z
authors.lastname: Kawakami
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kase
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D004365:Drugs, Chinese Herbal / Q000378:metabolism* / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D006035:Glycyrrhiza; D019695:Glycyrrhizic Acid / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D007564:Japan; D008297:Male; D008518:Medicine, East Asian Traditional; D018517:Plant Roots; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004365:Drugs, Chinese Herbal; C524644:Yi-Gan San; C119129:18alpha-glycyrrhetinic acid; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid