Dipsacussaponin C
Dipsacussaponin C potently induces procoagulant activity in platelets and leads to increased thrombus formation. DSC has an antinociceptive effect when it is administered supraspinally and GABAA, NMDA and non-NMDA receptors, but not opioid and GABAB receptors located at the supraspinal level, may be involved in DSC-induced antinociception. Dipsacus saponin C evoked hemolysis directly on the erythrocytes.
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Arch Pharm Res. 1999 Jun;22(3):317-319.
In vitro anticomplementary activity of hederagenin saponins isolated from roots of Dipsacus asper[Pubmed:
10403139]
Anticomplementary activity of hederagenin and related saponins isolated from Dipsacus asper was investigated in vitro. HN saponin F (3) was most potent with IC50 value of 3.7x10(-5) M followed by 3-O-beta-D-glucopyranosyl-(1->3)-alpha-L-rhamnopyranosyl-(1->2)-beta-L-+ ++arabi nopyranosyl hederagenin 28-O-beta-D-glucopyranosyl-(1->6)-beta-D-glucopyrano side (8), 3-O-beta-L-arabinopyranosyl hederagenin 28-O-beta-D-glucopyranosyl-(1->6)-beta-D-glucopyranoside (5), dipsacus saponin A (4), and hederagenin (1) on the classical pathway (CP) of complement system, while the saponins 3-5 did not show the inhibition of hemolysis and rather increase the hemolysis on the alternative pathway (AP). However, all of C-3 monodesmosides [prosapogenin CP (2), dipsacus saponin B (6), and dipsacus saponin C (7)] evoked hemolysis directly on the erythrocytes.
J Thromb Haemost . 2012 May;10(5):895-906.
Procoagulant and prothrombotic effects of the herbal medicine, Dipsacus asper and its active ingredient, dipsacus saponin C, on human platelets[Pubmed:
22405282]
Background: In spite of the growing popularity of herbal medicines and natural food supplements, their effects on cardiovascular homeostasis remain largely unknown, especially regarding pro-thrombotic risks.
Objective: In the present study, 21 herbal tea extracts were screened for the procoagulant activities on platelets, an important promoter of thrombosis to examine if herbal medicines or natural products may have prothrombotic risks. We discovered that Dipsacus asper (DA), known to have analgesic and anti-inflammatory effects, potently induced procoagulant activities in platelets. We tried to identify the active ingredient and elucidate the underlying mechanism.
Results: Among 10 major ingredients of DA, dipsacus saponin C (DSC) was identified as a key active ingredient in DA-induced procoagulant activities. DSC-induced procoagulant activities were achieved by the exposure of phosphatidylserine (PS) and PS-bearing microparticle generation that were caused by the alteration in the activities of phospholipid translocases: scramblase and flippase. These events were initiated by increased intracellular calcium and ATP depletion. Notably, DSC induced a series of apoptotic events including the disruption of mitochondrial membrane potential, translocation of Bax and Bak, cytochrome c release and caspase-3 activation. The key roles of apoptotic pathway and caspase activation were demonstrated by the reversal of DSC-induced PS exposure and procoagulant activities with the pretreatment of caspase inhibitors. Interestingly, EGTA reversed DSC-induced procoagulant activities and apoptotic events suggesting that an intracellular calcium increase may play a central role. These results were also confirmed in vivo where platelets of the rats exposed to DSC or DA exhibited PS exposure. Most importantly, DSC or DA administration led to increased thrombus formation.
Conclusion: These results demonstrate that herbal medicines or natural products such as DA or DSC might have prothrombotic risks through procoagulant activation of platelets.
Gen Pharmacol. 1996 Oct;27(7):1167-1172.
Antinociceptive mechanisms of dipsacus saponin C administered intracerebroventricularly in the mouse[Pubmed:
8981063]
1. Dipsacus saponin C (DSC) administered intracerebroventricularly (i.c.v.) showed an antinociceptive effect in a dose-dependent (from 3.75 to 30 micrograms) manner as measured by the tailflick assay. The antinociception induced by DSC at the dose of 30 micrograms was maintained at least 1 h. 2. Sulfated cholecystokinin (CCK, from 0.1 to 0.5 ng); muscimol (a GABAA receptor agonist, from 50 to 200 ng); MK-801 [(+/-)-5-methyl-10, 11-dihydro-5H-dibenzo (a,d) cyclohepten-5, 10-imine maleate, from 0.1 to 1 microgram], a noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist; or CNQX (6-cyano-7-nitroquinoxaline-2,3-dione, from 0.1 to 0.5 microgram), a non-NMDA receptor antagonist, injected i.c.v. significantly reduced the inhibition of the tail-flick response induced by DSC (30 micrograms) administered i.c.v. However, naloxone (an opioid receptor antagonist, 2 micrograms) or baclofen (a GABAB receptor antagonist, 10 ng) did not affect the inhibition of the tail-flick response induced by DSC. 3. The intrathecal (i.t.) injection of yohimbine (an alpha 2-adrenergic receptor antagonist, from 5 to 20 micrograms) and methysergide (a serotonin receptor antagonist, from 5 to 20 micrograms) but not naloxone (from 2 to 8 micrograms), significantly attenuated inhibition of the tail-flick response induced by DSC (30 micrograms) administered i.c.v. 4. Our results suggest that DSC has an antinociceptive effect when it is administered supraspinally and GABAA, NMDA and non-NMDA receptors, but not opioid and GABAB receptors located at the supraspinal level, may be involved in DSC-induced antinociception. Furthermore, DSC administered supraspinally may produce antinociception by stimulating descending alpha 2-adrenergic and serotonin pathways but not the opioidergic pathway.
J Ethnopharmacol . 2000 Jul;71(1-2):211-218.
Antinociceptive mechanisms of dipsacus saponin C administered intrathecally in mice[Pubmed:
10904165]
Dipsacus saponin C (DSC) administered intrathecally (i.t.) showed antinociceptive effect in a dose-dependent (from 3.75 to 30 microg) manner as measured by the tail-flick assay. The antinociception induced by DSC at the dose of 30 microg reached at peak 7.5 min and almost returned to the control level after 60 min. 5-Amino-valeric acid (5-AVA, a GABA(A) receptor antagonist, from 1 to 20 microg) and SR 95531 (a GABA(B) receptor antagonist, from 0.1 to 2 ng) dose-dependently attenuated i.t. administered DSC-induced increase of the inhibition of the tail-flick response. The i.t. injection of yohimbine (an alpha(2)-adrenergic receptor antagonist, from 1 to 20 microg) and methysergide (a serotonin receptor antagonist, from 1 to 20 microg), but not naloxone (from 2 to 8 microg), significantly attenuated inhibition of the tail-flick response induced by DSC (30 microg) administered i.t. Sulfated cholecystokinin (CCK, from 0.05 to 0.5 ng) injected i.t. significantly reduced the inhibition of the tail-flick response induced by DSC (30 microg) administered i.t. Our results suggest that DSC shows an antinociceptive effect when it is administered spinally and GABA(A), GABA(B), alpha(2)-adrenergic and serotonin receptors located at the spinal cord level, but not opioid receptors, may be involved in DSC-induced antinociception. Furthermore, CCK may play an important role for the modulation of i. t. injected DSC-induced antinociception.
J Nat Prod . 1993 Nov;56(11):1912-1916.
Triterpene glycosides from the roots of Dipsacus asper[Pubmed:
8289062]
The roots of Dipsacus asper have yielded two new triterpenoid saponins, dipsacus saponins B [1] and C [2], which have been characterized by chemical and spectral means and spectral means as hederagenin-3-O-beta-D-glucopyranosyl-(1-->4)-[alpha-L-rhamnopy ran osyl- (1-->6)]-beta-D-glucopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-a lpha- L-arabinopyranoside [1] and hederagenin-3-O-beta-D-xylopyranosyl-(1-->4)- beta-D-glucopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->3)-[alpha-L- rhamnopyranosyl-(1-->4)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L- arabinopyranoside [2].