Effect of Seven Tricyclic Diterpenoids from Needles ofTaxus mediavar.Hicksiion Stimulus-Induced Superoxide Generation, Tyrosyl or Serine/Threonine Phosphorylation and Translocation of Cytosolic Compounds to the Cell Membrane in Human Neutrophils

Abstract

Taxol has been widely used as an anticancer drug for ovarian, breast, lung and prostate cancer. Some kinds of Taxus plants are widely distributed in the Northeast Asia region. We have isolated seven tricyclic diterpenoids, taxinine, taxagifine, 5-O-cinnamoyltaxacin I triacetate, 5-decinnamoyltaxinine J, 5-cinnamoyl-9-acetyltaxicin I, taxacin and taxol from the needles of Taxus media var. Hicksii, and investigated their effects on stimulus-induced superoxide generation and translocation of cytosolic compounds to the cell membrane in human neutrophils. Six tricyclic diterpenoids used in this experiment suppressed the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and arachidonic acid (AA) in a concentration-dependent manner. Taxinine significantly suppressed the superoxide generation induced by phorbol 12-myristate 13-acetate (PMA). The compounds also suppressed fMLP- and AA-induced tyrosyl or PMA-induced serine/threonine phosphorylation, and translocation of cytosolic compounds, p47 (phox), p67 (phox) and Rac to the cell membrane in parallel with the suppression of the stimulus-induced superoxide generation.

Natural Taxanes: Developments Since 1828

“…Recently, it was reported that taxinine together with another six tricyclic diterpenoids suppress superoxide generation mainly via suppressing tyrosine or serine/threonine phosphorylation, and the translocation of cytosolic compounds to the cell membrane in human neutrophils. In addition, when concentration reached to the dosage suppressing superoxide generation needed, these compounds showed no effect of hemolysis …”

“…In addition, when concentration reached to the dosage suppressing superoxide generation needed, these compounds showed no effect of hemolysis. 46 4.3. 6/8/6-Taxanes 3: Basic Taxa-4(20),11-dienes (Table 4 and Figure 10)…”

Inhibitory Effects of Secoiridoids from the Roots of Gentiana straminea on Stimulus‐induced Superoxide Generation, Phosphorylation and Translocation of Cytosolic Compounds to Plasma Membrane in Human Neutrophils

“…It was reported previously that some triterpenoids Yagi-Chaves et al, 2006;He et al, 2008) and tricyclic diterpenoids (Tong et al, 2009) suppressed tyrosyl or serine/threonine phosphorylation of proteins and translocation to the plasma membrane of p47 phox , p67 phox and rac in parallel to the effect of stimulus-induced superoxide generation. The present study investigated the effects of five secoiridoids isolated from the root of G. straminea on superoxide generation, tyrosyl or serine/threonine phosphorylation of proteins and the translocation of cytosolic compounds, p47 phox , p67 phox and rac to the plasma membrane in human neutrophils and antioxidant activity.…”

“…It was reported previously that some triterpenoids (Chen et al , ; Yagi‐Chaves et al , ; He et al , ) and tricyclic diterpenoids (Tong et al , ) suppressed tyrosyl or serine/threonine phosphorylation of proteins and translocation to the plasma membrane of p47 phox , p67 phox and rac in parallel to the effect of stimulus‐induced superoxide generation. The present study investigated the effects of five secoiridoids isolated from the root of G .…”

Effects of Bioflavonoids from Taxus Media var. Hicksii on Superoxide Generation, Phosphorylation of Proteins and Translocation of Cytosolic Compounds to the Cell Membrane in Human Neutrophils

“…We have reported that tricyclic diterpenoid compounds isolated from T. media suppressed stimulus-induced superoxide generation in human neutrophils [9]. However, the corresponding research on bioflavonoids from T. media have not been reported.…”