Denudatin B
Denudatin B has nonspecific antiplatelet action at high concentration by inhibiting phosphoinositides breakdown induced by collagen and thrombin, it inhibits the aggregation and ATP release of washed rabbit platelets caused by platelet-activating factor (PAF) in a concentration-dependent manner. Denudatin B relaxes vascular smooth muscle by inhibiting the Ca2+ influx through voltage-gated and receptor-operated Ca2+ channels; its effect to increase cGMP may enhance the vasorelaxation. Denudatin B also shows potent 2, 2’-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activity.
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Thromb Res. 1990 Jul 1;59(1):121-30.
Inhibition of thrombin- and collagen-induced phosphoinositides breakdown in rabbit platelets by a PAF antagonist--denudatin B, an isomer of kadsurenone.[Pubmed:
2169076]
METHODS AND RESULTS:
Denudatin B, an isomer of kadsurenone, was isolated from Magnolia fargesii. It inhibited the aggregation and ATP release of washed rabbit platelets caused by platelet-activating factor (PAF) in a concentration-dependent manner. The IC50 on PAF (2 ng/ml)-induced aggregation was about 10 micrograms/ml. High concentration of Denudatin B (greater than 50 micrograms/ml) also inhibited the aggregation and ATP release of platelets caused by ADP, collagen, arachidonic acid and thrombin. However, shape change of platelets still existed. Prolongation of the incubation time with platelets could not cause further inhibition, and the aggregability of platelets could be restored after Denudatin B was washed out from platelets. Thrombin-induced thromboxane B2 formation was almost completely suppressed. In the absence of extracellular calcium (EGTA 1 mM), ATP release caused by thrombin was inhibited. Thrombin-induced rise of the intracellular calcium concentration was suppressed by Denudatin B, but not by BN52021 or kadsurenone. The generation of inositol phosphate in washed platelets caused by collagen, PAF and thrombin was also suppressed.
CONCLUSIONS:
The data indicate that PAF antagonist Denudatin B has nonspecific antiplatelet action at high concentration by inhibiting phosphoinositides breakdown induced by collagen and thrombin.
Eur J Pharmacol. 1990 Oct 2;187(1):39-47.
Vasorelaxing effect in rat thoracic aorta caused by denudatin B, isolated from the Chinese herb, magnolia fargesii.[Pubmed:
2176980]
Denudatin B is an antiplatelet agent isolated from the flower buds of Magnolia fargesii. We studied the effects of Denudatin B on the vasoconstriction of rat thoracic aorta induced by high potassium (K+) solution, norepinephrine (NE) and caffeine, and to elucidate its mode of action.
METHODS AND RESULTS:
The contraction of rat aorta caused by high K+ (60 mM) and cumulative concentrations of CaCl2 (0.03-3 mM) was inhibited concentration dependently by Denudatin B with an IC50 of 21.2 micrograms/ml. NE (3 microM)-induced phasic and tonic contractions of rat aorta were inhibited by pretreatment with Denudatin B (10-100 micrograms/ml). The relaxing action of Denudatin B persisted in denuded aorta, in Ca2(+)-free and EGTA (2 mM)-containing medium. The vasorelaxing effects were not affected by indomethacin (20 microM), hemoglobin (10 microM) or methylene blue (50 microM) and were not accompanied by PGI2 formation. In quin-2/AM-loaded cultured rat vascular smooth muscle cells, Denudatin B (100 micrograms/ml) inhibited the increase of intracellular calcium caused by NE (3 microM) in the presence or absence of extracellular calcium. Denudatin B did not affect the caffeine (10 mM)-induced contraction and the increase in intracellular calcium. Denudatin B (100 micrograms/ml) increased the cGMP, but not the cAMP level in intact and denuded aorta. The 45Ca2+ influx induced in rat aorta by high K+ (60 mM) or NE (3 microM) was markedly inhibited by Denudatin B in a concentration-dependent manner.
CONCLUSIONS:
These results indicate that Denudatin B relaxed vascular smooth muscle by inhibiting the Ca2+ influx through voltage-gated and receptor-operated Ca2+ channels; its effect to increase cGMP may enhance the vasorelaxation.
Pharmacogn Mag. 2015 Apr-Jun; 11(42): 235–241.
New free radical scavenging neolignans from fruits of Piper attenuatum[Pubmed:
25829760]
The aim was to study and identify free radicals scavenging and antihyperglycemic principles in fruit of Piper attenuatum.
METHODS AND RESULTS:
Bioassay guided identification of extracts possessing potent free radical scavenging activity, and isolation of compounds was done. Chloroform extract of P. attenuatum possessing potent radical scavenging activity was also evaluated for antihyperglycemic activity following oral glucose tolerance test in rats.
Nine neolignans namely, Denudatin B (1), iso-4', 5'-dimethoxy-3, 4-methylenedioxy-2'-oxo-Δ(3',5',8')-8.1'-lignan (2), lancifolin D (3), denudatin A (4), wallichinin (5), piperenone (6), lancifolin C (7), 2-oxo-piperol B (8), piperkadsin A (9) and a crotepoxide (10) was identified in Chloroform extract of P. attenuatum. Neolignans (1-9) displayed potent 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical and piperkadsin A (9) also displayed 1, 1-diphenyl-2-picrylhydrazyl radical scavenging activity. Analysis of structure-activity relationship revealed that presence of furan ring and methoxy groups is an important criterion to influence 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging potentials. Chloroform extract of P. attenuatum fruit could not display antihyperglycemic activity following oral glucose tolerance test in rats.
CONCLUSIONS:
Neolignans present in P. attenuatum fruits are potent free radical scavengers and this is the first report identifying these compounds and activities in this fruit.
