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Hum. Reprod. Advance Access published online on February 7, 2008
Human Reproduction, doi:10.1093/humrep/den001
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Active pharmaceutical ingredients and mechanisms underlying phasic myometrial contractions stimulated with the saponin extract from Paris polyphylla Sm. var. yunnanensis used for abnormal uterine bleeding

L. Guo1,{dagger}, J. Su1,{dagger}, B.W. Deng1,{dagger}, Z.Y. Yu1, L.P. Kang2, Z.H. Zhao1, Y.J. Shan1, J.P. Chen1, B.P. Ma2 and Y.W. Cong1,3

1 Department of Pathophysiology, Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850, China 2 Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China

3 Correspondence address. Tel: +86-10-68210077 ext. 931223; Fax: +86-10-68214653; E-mail: congyw{at}nic.bmi.ac.cn

BACKGROUND: Total steroidal saponins of Paris polyphylla Sm. var. yunnanensis (TSSP) have been widely used in China for the treatment of abnormal uterine bleeding (AUB). But until now, the main active constituents and the mechanisms underlying the pharmacological actions on uterine activity have not been described.

METHODS: Total steroidal saponins were extracted with EtOH and purified by chromatography. In vitro isometric contraction studies were performed using myometrial strips from estrogen-primed or pregnant rats. Intracellular calcium was monitored under a confocal microscope using Fluo-3 AM-loaded myometrial cells.

RESULTS: TSSP dose-dependently induced phasic myometrial contractions in vitro. Experiments with calcium channel blockers or kinase inhibitors demonstrated that the TSSP-stimulated myometrial contraction was mediated by an increase in [Ca2+]i via influx of extracellular calcium and release of intracellular calcium. Through bioassay-guided separation, it was found that total spirostanol saponins exhibited contractile activity in myometrium and Pennogenin-3-O-{alpha}-L-arabinofuranosyl(1->4)[{alpha}-L-rhamnopyranosyl(1->2)]-β-D-glucopyranoside (PARG) was identified as the active ingredient of TSSP. Furthermore, the contractile response of rat myometrium to PARG was significantly enhanced with advancing pregnancy.

CONCLUSIONS: These data provide evidence that myometrial contractility stimulated by TSSP results from [Ca2+]i increase and supports the possibility that some spirostanol gylcosides may represent a new type of contractile agonist for the uterus.

Key words: steroidal saponins/Paris polyphylla Sm. var. yunnanensis/myometrial contractility/abnormal uterine bleeding/active pharmaceutical ingredients

{dagger} These authors contributed equally to this work.

Submitted on May 22, 2007; resubmitted on December 17, 2007; accepted on January 2, 2008.


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