title: Two-step inhibitory effect of kanzo on oxytocin-induced and prostaglandin F2α-induced uterine myometrial contractions.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Takii Hospital, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan.
authors.forename: Genichiro
authors.initials: G
authors.lastname: Sumi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yasuda
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kanamori
authors.forename: Megumi
authors.initials: M
authors.lastname: Kajimoto
authors.forename: Akemi
authors.initials: A
authors.lastname: Nishigaki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Hisayuu
authors.initials: H
authors.lastname: Cho
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Okada
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kanzaki
mesh_terms: D000328:Adult; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005960:Glucosides / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry*; D019695:Glycyrrhizic Acid / Q000494:pharmacology; D006801:Humans; D039821:Monoterpenes; D009215:Myometrium / Q000187:drug effects / Q000502:physiology; D010121:Oxytocin / Q000494:pharmacology; D029596:Paeonia / Q000737:chemistry; D011247:Pregnancy; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects*; D006027:Glycosides
chemical_list: D001565:Benzoates; D001952:Bridged-Ring Compounds; D015237:Dinoprost; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D006034:Glycyrrhetinic Acid; D019695:Glycyrrhizic Acid; D039821:Monoterpenes; D010121:Oxytocin; C038462:shakuyaku-kanzoh-toh; C015423:peoniflorin; D006027:Glycosides
references.citation: J Agric Food Chem. 2011 Jul 27;59(14):7726-33
references.pmid: 21644799
references.citation: J Obstet Gynaecol Res. 2012 Jul;38(7):1004-10
references.pmid: 22568684
references.citation: Acta Pharmacol Sin. 2010 Apr;31(4):443-9
references.pmid: 20228825
references.citation: Support Care Cancer. 2009 Mar;17(3):315-20
references.pmid: 18839222
references.citation: J Steroid Biochem Mol Biol. 2004 Aug;91(4-5):211-8
references.pmid: 15336698
references.citation: World J Gastroenterol. 2006 Feb 7;12(5):760-4
references.pmid: 16521190
references.citation: Eur J Clin Invest. 1983 Aug;13(4):351-6
references.pmid: 6413222
references.citation: Nephron. 2002 Feb;90(2):240
references.pmid: 11818719
references.citation: Pharmacol Res Commun. 1984 Sep;16(9):875-84
references.pmid: 6594711
references.citation: Nephron Clin Pract. 2006;104(1):c28-32
references.pmid: 16685141
references.citation: Reproduction. 2006 Aug;132(2):343-53
references.pmid: 16885542
references.citation: Hum Reprod. 1996 Oct;11(10):2285-90
references.pmid: 8943542
references.citation: Mol Carcinog. 1996 Jul;16(3):157-64
references.pmid: 8688151
references.citation: Anticancer Res. 2012 Jul;32(7):2545-50
references.pmid: 22753712
references.citation: Biochem Biophys Res Commun. 1986 Jan 14;134(1):29-36
references.pmid: 3947327
references.citation: Am J Obstet Gynecol. 1985 Mar 15;151(6):757-61
references.pmid: 3976787
references.citation: Jpn J Pharmacol. 1996 Oct;72(2):111-8
references.pmid: 8912912
references.citation: Jpn J Pharmacol. 1985 Apr;37(4):395-9
references.pmid: 4010089
references.citation: J Med. 1995;26(3-4):163-74
references.pmid: 8558097
references.citation: Am J Chin Med. 2003;31(3):445-53
references.pmid: 12943175
references.citation: Biol Pharm Bull. 2007 Jan;30(1):145-9
references.pmid: 17202675
references.citation: Biol Pharm Bull. 1999 Mar;22(3):320-2
references.pmid: 10220293
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2004 Feb;70(2):137-48
references.pmid: 14683689
references.citation: J Cell Sci. 2006 May 1;119(Pt 9):1715-22
references.pmid: 16595547
references.citation: Endocrinol Jpn. 1977 Apr;24(2):155-62
references.pmid: 872820
references.citation: Nihon Sanka Fujinka Gakkai Zasshi. 1996 May;48(5):321-7
references.pmid: 8847457
references.citation: Clin Exp Obstet Gynecol. 2003;30(2-3):95-8
references.pmid: 12854851
references.citation: J Nat Med. 2009 Apr;63(2):200-3
references.pmid: 19050990