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  • Two-step inhibitory effect of kanzo on oxytocin-induced and prostaglandin F2α-induced uterine myometrial contractions.

Two-step inhibitory effect of kanzo on oxytocin-induced and prostaglandin F2α-induced uterine myometrial contractions.

Journal of natural medicines (2014-04-18)
Genichiro Sumi, Katsuhiko Yasuda, Chiharu Kanamori, Megumi Kajimoto, Akemi Nishigaki, Tomoko Tsuzuki, Hisayuu Cho, Hidetaka Okada, Hideharu Kanzaki
ABSTRACT

We previously reported that shakuyaku-kanzo-to, a kampo medicine consisting of shakuyaku and kanzo, has an inhibitory effect on myometrial contractions in pregnant women. In this study, we evaluated the effects of kanzo, glycyrrhizin (a major component of kanzo), glycyrrhetinic acid (GA; a major metabolite of glycyrrhizin), shakuyaku, and paeoniflorin (a major component of shakuyaku) on agonist-induced contractions of the uterus of pregnant humans and rats. We prepared myometrial strips from the uterus of pregnant humans and rats and induced contractions with oxytocin (50 μU/mL) or prostaglandin F2α (PGF2α) (10(-7) or 10(-6) M). Kanzo (250 μg/mL) and GA (5 × 10(-6) M) inhibited the oxytocin-induced and PGF2α-induced contractions in pregnant human and rat myometrium, but shakuyaku (250 μg/mL), paeoniflorin (10(-5) M), and glycyrrhizin (10(-5) M) did not inhibit contractions in either. Interestingly, kanzo and GA showed an inhibitory effect after temporarily enhancing the PGF2α-induced contractions in the rat myometrium, but not in the human myometrium. These results suggest that kanzo has at least a two-step inhibitory effect on the myometrial contractions that originate from the kanzo itself and a metabolite of glycyrrhizin in kanzo. Furthermore, kanzo was found to be safe for inhibiting PGF2α-induced contractions in humans because it did not temporarily enhance PGF2α-induced contractions.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Oxytocin
Sigma-Aldrich
Oxytocin, lyophilized powder, ~15 IU/mg solid (Prepared from synthetic oxytocin)
Sigma-Aldrich
Paeoniflorin, ≥98% (HPLC)
USP
Oxytocin, United States Pharmacopeia (USP) Reference Standard
Oxytocin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
18β-Glycyrrhetinic acid, 97%
Enoxolone, European Pharmacopoeia (EP) Reference Standard
Supelco
Paeoniflorin, analytical standard
Sigma-Aldrich
Oxytocin acetate salt hydrate, ≥97% (HPLC)