Ginsenoside Re, one of the main constituents of Panax ginseng, possesses novel antioxidant and anti-inflammatory properties. However, the pharmacological mechanism of ginsenoside Re in dopaminergic degeneration remains elusive. We suggested that protein kinase C (PKC) δ mediates methamphetamine (MA)-induced dopaminergic toxicity. Treatment with ginsenoside Re significantly attenuated methamphetamine-induced dopaminergic degeneration in vivo by inhibiting impaired enzymatic antioxidant systems, mitochondrial oxidative stress, mitochondrial translocation of protein kinase Cδ, mitochondrial dysfunction, pro-inflammatory microglial activation, and apoptosis. These protective effects were comparable to those observed with genetic inhibition of PKCδ in PKCδ knockout (-/-) mice and with PKCδ antisense oligonucleotides, and ginsenoside Re did not provide any additional protective effects in the presence of PKCδ inhibition. Our results suggest that PKCδ is a critical target for ginsenoside Re-mediated protective activity in response to dopaminergic degeneration induced by MA.

Tumor angiogenesis is required for tumor development and is stimulated by angiogenic inducers like VEGF (vascular endothelial growth factor). Our previous study demonstrated that STAT3 (signal transducer and activator of transcription 3) up-regulates HIF-1alpha (hypoxia inducible factor-1alpha) protein stability and enhances HIF-1-mediated VEGF expression in hypoxic solid tumor cells, thus suggesting that the inhibition of STAT3 signaling may have clinical applications. In this study, we examined in vitro and in vivo, whether caffeic acid (CA) or its derivative CADPE [3-(3,4-dihydroxy-phenyl)-acrylic acid 2-(3,4-dihydroxy-phenyl)-ethyl ester] exert anticancer activity by targeting STAT3. It was found that CA or CADPE significantly inhibit STAT3 activity, and that this in turn down-regulates HIF-1alpha activity. Consequently, sequential blockade of STAT3 and HIF-1alpha resulted in the down-regulation of VEGF by inhibiting their recruitment to the VEGF promoter. In mice bearing a Caki-I carcinoma, both CA and CADPE retarded tumor growth and suppressed STAT3 phosphorylation, HIF-1alpha expression, vascularization and STAT3-inducible VEGF gene expression in tumors. Taken together, our results demonstrate that CA and CADPE are potential inhibitors of STAT3 and that they suppress tumor angiogenesis by inhibiting the activity of STAT3, the expression of HIF-1alpha and VEGF.

This study examined the role of protein kinase C (PKC) isozymes in methamphetamine (MA)-induced dopaminergic toxicity. Multiple-dose administration of MA did not significantly alter PKCα, PKCβI, PKCβII, or PKCζ expression in the striatum, but did significantly increase PKCδ expression. Gö6976 (a co-inhibitor of PKCα and -β), hispidin (PKCβ inhibitor), and PKCζ pseudosubstrate inhibitor (PKCζ inhibitor) did not significantly alter MA-induced behavioral impairments. However, rottlerin (PKCδ inhibitor) significantly attenuated behavioral impairments in a dose-dependent manner. In addition, MA-induced behavioral impairments were not apparent in PKCδ knockout (–/–) mice. MA-induced oxidative stress (i.e., lipid peroxidation and protein oxidation) was significantly attenuated in rottlerin-treated mice and was not apparent in PKCδ (–/–) mice. Consistent with this, MA-induced apoptosis (i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive apoptotic cells) was significantly attenuated in rottlerin-treated mice. Furthermore, MA-induced increases in the dopamine (DA) turnover rate and decreases in tyrosine hydroxylase (TH) activity and the expression of TH, dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) were not significantly observed in rottlerin-treated or PKCδ (–/–) mice. Our results suggest that PKCδ gene expression is a key mediator of oxidative stress and dopaminergic damage induced by MA. Thus, inhibition of PKCδ may be a useful target for protection against MA-induced neurotoxicity.

Abstract:A method for the separation and quantification of three flavonoids and one isocoumarin by reverse-phase high performance liquid chromatography (HPLC) has been developed and validated. Four constituents present in a crude ethanolic extract of the flowers of Coryloposis coreana Uyeki, were analyzed. Bergenin, quercetin, quercitrin and isosalipurposide were used as calibration standards. In the present study, an excellent linearity was obtained with an r 2 higher than 0.999. The chromatographic peaks showed good resolution. In combination with other validation data, including precision, specificity, and accuracy, this method demonstrated good reliability and sensitivity, and can be conveniently used for the quantification of bergenin, quercetin, quercitrin and isosalipurposide in the crude ethanolic extract of C. coreana Uyeki flos. Furthermore, the plant extracts were analyzed with HPLC to determine the four constituents and compositional differences in the extracts obtained under different extraction conditions. Several extracts of them which was dependent on the ethanol percentage of solvent were also analyzed for their antimicrobial and antioxidant activities. One hundred % ethanolic extract from C. coreana Uyeki flos showed the best antimicrobial activity against the methicillin-resistant Staphylococcus aureus (MRSA) strain. Eighty % ethanolic extract showed the best antioxidant activity and phenolic content. Taken of all, these results suggest that the flower of C. coreana Uyeki flos may be a useful source for the cure and/or prevention of septic arthritis, and the validated method was useful for the quality control of C. coreana Uyeki.