Isolation of phorbol esters from euphorbia grandicornis and evaluation of protein kinase c- and human platelet-activating effects of euphorbiaceae diterpenes

Ju Ying Tsai, Dóra Rédei, Peter Forgo, Yu Li, Andrea Vasas, J. Hohmann, Chin Chung Wu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Human platelets contain conventional (α and β) and novel isoforms of PKC (δ and θ), and PKC activation can result in platelet aggregation and secretion reaction that are important for thrombus formation. Several tumor-promoting Euphorbiaceae diterpenes are known to act as direct activators of PKC, but many types of such diterpenes have not been studied as platelet stimulators. In the present study, two new and five known phorbol esters were isolated from Euphorbia grandicornis. Two of the isolated phorbol esters together with compounds representing ingenane, jatrophane, and myrsinane structural types were studied on PKC activation and platelet stimulation. The investigated phorbol esters and ingenane esters induced blood platelet aggregation and ATP secretion. PKC activation was demonstrated by inducing membrane translocation of PKCs, phosphorylation of PKC substrates, and activation of PKC signaling pathways. The PKC-activating effect of the compounds correlated well with their efficacy to cause platelet stimulation. Moreover, by using an isoform-specific PKC inhibitor, it was found that besides conventional PKCs novel PKCs also play a positive role in platelet activation caused by phorbol/ingenane esters, especially in regulating platelet aggregation. The present results suggest that platelets afford a useful model for studying PKC activators of natural origin or their chemical derivatives.

Original languageEnglish
Pages (from-to)2658-2666
Number of pages9
JournalJournal of Natural Products
Volume79
Issue number10
DOIs
Publication statusPublished - Oct 28 2016

Fingerprint

Euphorbiaceae
Euphorbia
Diterpenes
Phorbol Esters
Platelets
Protein Kinases
Blood Platelets
Platelet Aggregation
Platelet Activation
Chemical activation
Protein Isoforms
Agglomeration
Esters
Thrombosis
Adenosine Triphosphate
Phosphorylation
Membranes
Tumors
Blood
ingenane

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

Isolation of phorbol esters from euphorbia grandicornis and evaluation of protein kinase c- and human platelet-activating effects of euphorbiaceae diterpenes. / Tsai, Ju Ying; Rédei, Dóra; Forgo, Peter; Li, Yu; Vasas, Andrea; Hohmann, J.; Wu, Chin Chung.

In: Journal of Natural Products, Vol. 79, No. 10, 28.10.2016, p. 2658-2666.

Research output: Contribution to journalArticle

Tsai, Ju Ying ; Rédei, Dóra ; Forgo, Peter ; Li, Yu ; Vasas, Andrea ; Hohmann, J. ; Wu, Chin Chung. / Isolation of phorbol esters from euphorbia grandicornis and evaluation of protein kinase c- and human platelet-activating effects of euphorbiaceae diterpenes. In: Journal of Natural Products. 2016 ; Vol. 79, No. 10. pp. 2658-2666.
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