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
Open Access
- 31 January 2008
- journal article
- Published by Oxford University Press (OUP) in Human Reproduction
- Vol. 23 (4), 964-971
- https://doi.org/10.1093/humrep/den001
Abstract
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. 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. 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-α-L-arabinofuranosyl(1→4)[α-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. 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.Keywords
This publication has 22 references indexed in Scilit:
- Cytosolic calcium concentration is reduced by photolysis of a nitrosyl ruthenium complex in vascular smooth muscle cellsNitric Oxide, 2006
- abnormal Uterine BleedingThe Nurse Practitioner, 2005
- Alternative medical and surgical options to hysterectomyBest Practice & Research Clinical Obstetrics & Gynaecology, 2005
- Characterization of intracellular Ca2+ stores in gallbladder smooth muscleAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2005
- Characterization of Contractile Activity and Intracellular Ca2+ Signalling in Mouse MyometriumJournal of the Society for Gynecologic Investigation, 2004
- Assessment of abnormal bleeding in menopausal women: an updatePost Reproductive Health, 2003
- The Bioactivity of Saponins: Triterpenoid and Steroidal GlycosidesDrug Metabolism and Drug Interactions, 2000
- Stimulation of Oscillatory Uterine Contraction by the PCB Mixture Aroclor 1242 May Involve Increased [Ca2+]ithrough Voltage-Operated Calcium ChannelsToxicology and Applied Pharmacology, 1999
- Effects of Prostanoids on the Rat’s Myometrium in Vitro during Pregnancy1Biology of Reproduction, 1992
- Steroid saponins from Paris polyphylla Sm.-supplement.CHEMICAL & PHARMACEUTICAL BULLETIN, 1982