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.
These results suggest that lipid-soluble substances with low polarity derived from kanzo are responsible for the inhibitory effect of shakuyaku-kanzo-to on myometrial contraction.
Pain affects many cancer patients, and in advanced stages of the disease it can significantly affect the quality of their lives. Morphine has long been the 'gold standard' for the treatment of cancer pain. However, its side-effects, particularly sedation and cognitive impairment at high doses, have encouraged the use of 'opioid rotation'. The transdermal fentanyl patch has advantages over oral morphine, with reduced side-effects and increased convenience in practical usage. The side-effects were reduced in patients who changed to the fentanyl patch, but rescue analgesia was often needed because of the decrease of fentanyl release from the patch, especially on the patch replacement day. We have developed a three-cycle fentanyl patch system that provided an appropriate pain control, and this system should be considered for pain relief in cancer patients.
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