dinoprost and peoniflorin

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.

Topics: Adult; Animals; Benzoates; Bridged-Ring Compounds; Dinoprost; Drug Combinations; Drugs, Chinese Herbal; Female; Glucosides; Glycyrrhetinic Acid; Glycyrrhiza; Glycyrrhizic Acid; Humans; Monoterpenes; Myometrium; Oxytocin; Paeonia; Pregnancy; Rats; Uterine Contraction

Paeoniae Radix (the roots of Paeonia lactiflora Pallas) is a crude drug that is used in Asia and Europe to improve blood flow. We studied its vasodilator effect and mechanisms of action in vitro. The extract from Paeoniae Radix (PRE) relaxed prostaglandin F2a-precontracted aortic ring preparations of isolated rat aorta that contained endothelium. Relaxation by PRE did not occur in specimens without endothelium, and was inhibited by pretreatment with 10(-4) M NG-nitro-1-arginine methyl ester. Paeoniflorin and paeonol, the main active components of Paeoniae Radix, lacked a vasodilator effect. The effect of the component gallotannin was examined after treating PRE with tannase, but the product lacked a vasodilator effect. Pentagalloylglucose, hexagalloylglucose, heptagalloylglucose, and octagalloylglucose were extracted from PRE; they relaxed aortic rings with endothelium, but failed to relax aortic rings without endothelium. We conclude that PRE exhibits an endothelium-dependent vasodilator effect on isolated rat aorta. The active component is gallotannin.

Topics: Acetophenones; Animals; Aorta, Thoracic; Asia; Benzoates; Bridged-Ring Compounds; Dinoprost; Endothelium, Vascular; Europe; Gallic Acid; Glucosides; In Vitro Techniques; Male; Monoterpenes; Muscle, Smooth, Vascular; Plant Extracts; Plant Roots; Plants, Medicinal; Rats; Rats, Wistar; Vasodilation