Effect of 18¦Â-glycyrrhetinic acid and hydroxypropyl ¦Ãcyclodextrin complex on indomethacin-induced small intestinal injury in mice
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- 作者：Tsukasa Ishida ; Ikuya Miki ; Toshihito Tanahashi ; Saori Yagi ; Yasuyuki Kondo ; Jun Inoue ; Shoji Kawauchi ; Sin Nishiumi ; Masaru Yoshida ; Hideko Maeda ; Chisato Tode ; Atsuko Takeuchi ; Hirokazu Nakayama ; Takeshi Azuma ; Shigeto Mizuno
- 关键词：Glycyrrhizin ; 18¦Â-Glycyrrhetinic acid ; Hydroxypropyl ¦Ãcyclodextrin ; Indomethacin ; Small intestinal injury
- 刊名：European Journal of Pharmacology
- 出版年：2013
- 出版时间：15 August, 2013
- 年：2013
- 卷：714
- 期：1-3
- 页码：125-131
- 全文大小：757 K
文摘
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, 18¦Â-glycyrrhetinic acid, and dipotassium glycyrrhizinate, were compared in vitro cell culture. The most prominent inhibitory effect on the tumor necrosis factor-¦Á (TNF-¦Á) production was observed with the administration of 18¦Â-glycyrrhetinic acid as an active metabolite of glycyrrhizin. In this study, a complex compound of 18¦Â-glycyrrhetinic acid and hydroxypropyl ¦Ãcyclodextrin was examined to improve the oral bioavailability. After administration of this complex to indomethacin treated mice, a significantly high plasma concentration of 18¦Â-glycyrrhetinic acid was detected using the tandem mass spectrometry coupled with the HPLC. Furthermore, the complex form of 18¦Â-glycyrrhetinic acid and hydroxypropyl ¦Ãcyclodextrin reduced mRNA expressions of TNF-¦Á, interleukin (IL)-1¦Â, and IL-6, which was histologically confirmed in the improvement of indomethacin-induced small intestinal damage. These results suggest that the complex of 18¦Â-glycyrrhetinic acid and hydroxypropyl ¦Ãcyclodextrin has the potential therapeutic value for preventing the adverse effects of indomethacin-induced small intestinal injury.