Pennogenin glycosides with a spirostanol structure are strong platelet agonists: structural requirement for activity and mode of platelet agonist synergism

Abstract

Summary. Background: Steroidal saponins have long attracted scientific attention, due to their structural diversity and significant biological activities. For example, total steroidal saponins extracted from the rhizome of Paris polyphylla Sm. var. yunnanensis (TSSPs) constitute an effective treatment for abnormal uterine bleeding. Objective: To determine the active constituents in TSSPs and elucidate the mechanisms that underlie their in vivo pharmacologic actions on hemostasis. Methods: Steroidal saponins were purified by chromatography, and their effects upon hemostasis and platelet function were evaluated by tail bleeding time in mice and rats, aggregometry, flow cytometry and Western blotting. Results: TSSPs promoted hemostasis in vivo and dose-dependently induced rat or human platelet aggregation in vitro. Using bioassay-guided separation, four known pennogenin glycosides with a spirostanol structure were identified as the active ingredients of TSSPs. A structure-activity assay showed that the aglycone and sugar moieties of pennogenin glycosides are both essential for their aggregatory activity. Their synergistic actions on platelet aggregation were observed with pennogenin glycosides and with other known platelet agonists, suggesting that these glycosides are platelet agonists. Aggregation in response to the pennogenin glycosides involved a IIb b 3 activation, was inhibited by cAMP, was dependent upon extracellular calcium, secreted ADP and thromboxane synthesis, and was mediated by phosphatidylinositol-3-kinase. Conclusion: We identified pennogenin glycosides with a spirostanol structure as the active ingredients of Paris polyphylla Sm. var. yunnanensis in promoting hemostasis in vivo. Their mode of their action on platelets suggests that they represent a new type of platelet agonist.

Study on hemostatic activities of the rhizome ofParis bashanensis

“…The hemostatic of steroidal saponins was dependent on their structures, especially on the nature, number and sequence of the sugars in the saponins, while extending sugar units of pennogenin glycosides from diglycoside to triglycosides, and then to tetraglycosides, also significantly enhanced their activities. Their effects upon hemostasis and platelet function were evaluated and identified as the active ingredients of total steroidal saponins by Fu et al (2008).…”

Steroidal saponins with induced platelet aggregation activity from the aerial parts of Paris verticillata

“…Recently, Cong's group reported that pennogenin glycosides with a spirostanol structure isolated from Paris polyphylla var. yunnanensis were the active ingredients in promoting hemostasis in vivo and directly induced platelet activation by dense granule secretion of ADP, which in turn activated the P2Y1 and P2Y12 receptor signaling pathways [2,3]. Due to long growth cycle and the expansion of industrial demand, the wild populations of this genus are dramatically decreased, which reminds us to find alternative resources urgently.…”

Qualitative and quantitative analysis of steroidal saponins in crude extracts from Paris polyphylla var. yunnanensis and P. polyphylla var. chinensis by high performance liquid chromatography coupled with mass spectrometry

“…It is one of the major components of many well-known prepared Chinese medicines like Yunnan Baiyao Powder, Gongxuening Capsules and Jidesheng Sheyao Tablet, and has frequently played an important role in clinics for immunity adjustment and treating fractures, parotitis, tumours, analgesia and bleeding [2]. A lot of steroidal saponins have been isolated and identified from Chonglou and other species of the genus Paris [2], and they were considered as the major effective constituents for significant biological activities, such as antitumour [3,4], antifungal [5], inhibitory activities against abnormal uterine bleeding [6,7], chronotropic effects on spontaneous beating of myocardial cells [8], and protective effects on ethanol-or indomethacin-induced gastric mucosal lesions in rats [9]. The structures of these saponins were mainly classified into two types, pennogenin (PNA-PNE) and diosgenin (DSF-DSK), according to the differences of steroidal aglycones (Fig.…”