Structural requirement of spirostanol glycosides for rat uterine contractility and mode of their synergism.
OBJECTIVE
Total steroidal saponins extracted from the rhizome of Paris polyphylla (TSSP) have been used in China for the treatment of abnormal uterine bleeding. The aim of this study was to analyse the structure-activity relationship of steroidal saponins purified from P. polyphylla Sm. var. yunnanensis on rat myometrial contractions, and investigate the synergism among themselves as well as with known inherent agonists, such as Prostaglandin F(2alpha) (PGF-2alpha).


METHODS
In this study, 22 steroidal saponins purified from TSSP were screened for their contractile activity in isolated uterine strips from estrogen-primed rats.


RESULTS
It was shown that spirostanol glycosides exhibited inducible or inhibitory activity in rat uterine contraction based on the difference of their structures, which was not only attributed in part to the number, the length and the position of sugar side chains attached by a glycoside, but also related to the structure of the aglycone. Furthermore, synergistic actions were observed among pennogenin or diosgenin glycosides as well as with the known inherent agonist PGF-2alpha, indicating they may share, at least in part, similar pathways with PGF-2alpha in stimulating myometrial contractions. Finally, the contractile response of rat myometrium to spirostanol glycosides was significantly enhanced with advancing pregnancy.


CONCLUSIONS
Together, these data support the possibility that some spirostanol glycosides may represent a new type of contractile agonist for the uterus and their synergism may be responsible for the therapeutic effect of TSSP on abnormal uterine bleeding.
Yu
Zu-Yin
ZY
Department of Pathophysiology, Beijing Institute of Radiation Medicine, Beijing, China.
Guo
Lin
L
Wang
Bo
B
Kang
Li-Ping
LP
Zhao
Zhen-Hu
ZH
Shan
Ya-Jun
YJ
Xiao
He
H
Chen
Jia-Pei
JP
Ma
Bai-Ping
BP
Cong
Yu-Wen
YW
D000818:Animals; D015237:Dinoprost / Q000378:metabolism; D004144:Diosgenin / Q000494:pharmacology; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D019668:Liliaceae / Q000737:chemistry*; D009215:Myometrium / Q000187:drug effects* / Q000502:physiology; D010840:Phytosterols / Q000737:chemistry / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D027343:Rhizome; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004365:Drugs, Chinese Herbal; D004967:Estrogens; D010840:Phytosterols; D012503:Saponins; D015237:Dinoprost; D004144:Diosgenin