| Description: |
Euxanthone has vasorelaxation effect, may be through multiple pathways involved PKC-mediated signal pathway and calcium-independent pathway, it induces its vasodilator effect through inhibition of calcium-sensitive mechanisms activated by protein kinase C. Euxanthone-induced neurite outgrowth was actively regulated by transcription factor E2F-5 via PKC pathway, it-induced differentiation of the neuroblastoma BU-1 cells may be mediated through the differential expression of PKC-alpha, -beta, -delta, -lambda and -zeta isoforms. |
| In vitro: |
| Vascul Pharmacol. 2006 Aug;45(2):96-101. | | Vasorelaxant effect of euxanthone in the rat thoracic aorta.[Pubmed: 16678494] | This study was undertaken to investigate the effect of Euxanthone on isolated rat thoracic aorta.
METHODS AND RESULTS:
Euxanthone concentration-dependently relaxed high K+-induced sustained contractions with IC50 values of 32.28+/-1.73 microM and this inhibition was antagonized by increasing the Ca2+ concentration in the medium. These results indicated that Euxanthone may have calcium antagonistic property. Euxanthone also relaxed norepinephrine (NE)-induced sustained contractions with IC50 values of 32.50+/-2.15 microM and this relaxant effect was unaffected by the removal of endothelium or by the presence of propranolol, indomethacin, glibenclamide or N(omega)-nitro-L-arginine. Moreover, Euxanthone inhibited both the phasic and tonic contractions induced by NE in a concentration-dependent manner and showed more potent inhibition on phasic contraction (P < 0.01). Pre-treatment with Euxanthone inhibited vascular contraction induced by phorbol 12, 13-dibutyrate (PDBu), a protein kinase C (PKC) agonist, in either the presence or absence of Ca2+ in the solution with IC50 values of 20.15+/-1.56 and 18.30+/-1.62 microM, respectively. However, when the tissues were treated with Euxanthone after the PDBu-induced contraction had reached a steady state, the tension was not affected by Euxanthone. This study also showed that the inhibitory effect of pre-treatment of Euxanthone was more potent than the post-treatment after the tension had reached a steady state.
CONCLUSIONS:
These results suggested that the vasorelaxation of Euxanthone may be through multiple pathways involved PKC-mediated signal pathway and calcium-independent pathway besides the direct inhibition of calcium influx and its vasorelaxant effect is more active on calcium-independent pathway and more sensitive to the initial stage of contraction. | | Planta Med. 2001 Jul;67(5):400-5. | | Expression of protein kinase C isoforms in euxanthone-induced differentiation of neuroblastoma cells.[Pubmed: 11488451] | Euxanthone, a potent neuritogenic compound isolated from the roots of the medicinal herb Polygala caudata, has recently been shown to induce the differentiation of murine neuroblastoma Neuro 2A (BU-1) cells.
METHODS AND RESULTS:
In this study, the role of protein kinase C (PKC) and the expression of various PKC isoforms in Euxanthone-treated BU-1 cells were examined. mRNA phenotyping using the reverse-transcription polymerase chain reaction (RT-PCR) showed that BU-1 cells express six different PKC isoforms, namely PKC-alpha, -beta, -delta, -epsilon, -lambda, and -zeta. Differential regulation and expression of PKC isoforms was observed in BU-1 cells treated with 100 microM Euxanthone. PKC-apha, -beta, -delta, -lambda and -zeta were all up-regulated, with 1.7- to 9.5-fold increase, at around 30 to 60 minutes after Euxanthone treatment. The expression level of PKC-epsilon remained relatively constant during the treatment. PKC-gamma, -eta, and -theta were not detected in both untreated and Euxanthone-treated BU-1 cells. Staurosporine, a broad spectrum PKC inhibitor, was found to inhibit both spontaneous and Euxanthone-induced neuritogenesis in BU-1 cells. A significant reduction of the Euxanthone-induced neuritogenic effect was also observed when the PKC isoform-specific inhibitor Go6976 was included in the culture.
CONCLUSIONS:
These results suggest that the Euxanthone-induced differentiation of the neuroblastoma BU-1 cells may be mediated through the differential expression of PKC-alpha, -beta, -delta, -lambda and -zeta isoforms. |
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