title: Effect of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin complex on indomethacin-induced small intestinal injury in mice.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal injury is a serious clinical event with recent advances of diagnostic technologies, but a successful therapeutic method to treat such injuries is still lacking. Licorice, a traditional herbal medicine, and its derivatives have been widely used for the treatment of a variety of diseases due to their extensive biological actions. However, it is unknown whether these derivatives have an effect on NSAIDs-induced small intestinal damage. Previously, the anti-inflammatory effects of three compounds extracted from the licorice root, glycyrrhizin, 18β-glycyrrhetinic acid, and dipotassium glycyrrhizinate, were compared in vitro cell culture. The most prominent inhibitory effect on the tumor necrosis factor-α (TNF-α) production was observed with the administration of 18β-glycyrrhetinic acid as an active metabolite of glycyrrhizin. In this study, a complex compound of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin was examined to improve the oral bioavailability. After administration of this complex to indomethacin treated mice, a significantly high plasma concentration of 18β-glycyrrhetinic acid was detected using the tandem mass spectrometry coupled with the HPLC. Furthermore, the complex form of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin reduced mRNA expressions of TNF-α, interleukin (IL)-1β, and IL-6, which was histologically confirmed in the improvement of indomethacin-induced small intestinal damage. These results suggest that the complex of 18β-glycyrrhetinic acid and hydroxypropyl γcyclodextrin has the potential therapeutic value for preventing the adverse effects of indomethacin-induced small intestinal injury.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ishida
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Saori
authors.initials: S
authors.lastname: Yagi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kondo
authors.forename: Jun
authors.initials: J
authors.lastname: Inoue
authors.forename: Shoji
authors.initials: S
authors.lastname: Kawauchi
authors.forename: Sin
authors.initials: S
authors.lastname: Nishiumi
authors.forename: Masaru
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hideko
authors.initials: H
authors.lastname: Maeda
authors.forename: Chisato
authors.initials: C
authors.lastname: Tode
authors.forename: Atsuko
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Nakayama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Shigeto
authors.initials: S
authors.lastname: Mizuno
mesh_terms: D000818:Animals; D001682:Biological Availability; D005786:Gene Expression Regulation / Q000187:drug effects; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007213:Indomethacin / Q000009:adverse effects*; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007421:Intestine, Small / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012995:Solubility; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D047408:gamma-Cyclodextrins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D047408:gamma-Cyclodextrins; C479659:hydroxypropyl-gamma-cyclodextrin; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid; D007213:Indomethacin
keywords: 18β-Glycyrrhetinic acid; Glycyrrhizin; Hydroxypropyl γcyclodextrin; Indomethacin; Small intestinal injury