Anti-platelet effects of bioactive compounds isolated from the bark of Rhus verniciflua Stokes.

Quality Control of Herbal Medicine Department, Korea Institute of Oriental Medicine, Daejeon 461-24, South Korea.
Journal of Ethnopharmacology (Impact Factor: 2.76). 07/2006; 106(1):62-9. DOI: 10.1016/j.jep.2005.12.015
Source: PubMed

ABSTRACT It has previously been shown that EtOAc extracts of Rhus verniciflua Stokes (RVS) inhibit the platelet aggregation response. In this report, bioassay-guided fractionation using ADP-, arachidonic acid-, and collagen-induced human platelet aggregation by a whole blood aggregometer yielded the bioactive compounds isomaltol and pentagalloyl glucose from different highly effective fractions. In addition, column chromatography of fractions from RVS yielded another five compounds: butin, fisetin, sulfuretin, butein and 3,4',7,8-tetrahydroxyflavone. We investigated the effects of bioactive compounds from RVS fractions on several markers of platelet activation using receptor expression on platelet membranes, including glycoprotein IIb/IIIa (CD41), GPIIb/IIIa-like expression (PAC-1) and P-selectin (CD62), and intracelluar calcium mobilization responses by flow cytometry in healthy subjects. Dose-dependent inhibition of platelet aggregation and significantly decreased platelet activation were observed for the isomaltol- and pentagalloyl glucose-treated platelets, respectively. These results show that isomaltol and pentagalloyl glucose from the bark of Rhus verniciflua Stokes have potent anti-platelet activity and emphasize the need to further examine the mechanism of these active compounds for platelet modulation.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Rhus verniciflua Stokes (RVS) has been used as a traditional herbal medicine for its various biological activities including anti obesity effects. Activity guided separation led to the identification of the anti adipogenic functions of butein. Butein a novel anti adipogenic compound robustly suppressed lipid accumulation and inhibited expression of adipogenic markers. Molecular studies showed that activated TGFβ and suppressed STAT3 signaling pathways were mediated by butein. Analysis of the temporal expression profiles suggests that TGFβ signaling precedes the STAT3 in the butein mediated anti adipogenic cascade. Small interfering RNA mediated silencing of STAT3 or SMAD2/3 blunted the inhibitory effects of butein on adipogenesis indicating that an interaction between two signaling pathways is required for the action of butein. Upon butein treatments, stimulation of TGFβ signaling was still preserved in STAT3 silenced cells, whereas regulation of STAT3 signaling by butein was significantly impaired in SMAD2/3 silenced cells, further showing that TGFβ acts upstream of STAT3 in the butein mediated anti adipogenesis. Taken together, the present study shows that butein, a novel anti adipogenic compound from RVS, inhibits adipocyte differentiation through the TGFβ pathway followed by STAT3 and PPARγ signaling, further implicating potential roles of butein in TGFβ and STAT3 dysregulated diseases.
    The Journal of Lipid Research 03/2013; · 4.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A simple, sensitive, and precise reversed-phase liquid chromatographic method was developed for the quantitative determination of 4 bioactive phenolic compounds (gallic acid, fustin, fisetin, and sulfuretin) from the stem extract of Rhus verniciflua stokes. Chromatographic analysis was performed on a Capcell Pak C18 column (150×4.6mm, 3μm) with a mobile phase consisting of 0.1% formic acid and 90% acetonitrile at a flow rate of 1mL/min. Quantitation was performed using a UV-vis detector at 260nm. The method was validated in terms of selectivity, linearity, accuracy, precision, and recovery. Excellent linear behavior was observed over the investigated concentration range (10-500μg/mL for gallic acid, fustin, and fisetin; 0.5-100μg/mL for sulfuretin) with correlation coefficient (r(2)) values >0.99. The intra- and inter-day precision over the concentration range of compounds was less than 6.65% (relative standard deviation) and the accuracy was between 92.42% and 103.62%. The mean recoveries for all the analytes were more than 92.18%. This method was successfully applied for the analysis of bioactive phenolic compounds in the R. verniciflua extracts.
    Food Chemistry 12/2013; 141(4):3813-9. · 3.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sulfuretin, a potent anti-oxidant, has been thought to provide health benefits by decreasing the risk of oxidative stress-related diseases. In this study, we investigated the mechanisms of sulfuretin protection of neuronal cells from cell death induced by the Parkinson's disease (PD)-related neurotoxin 6-hydroxydopamine (6-OHDA). We examined whether sulfuretin acts as an anti-oxidant to reduce oxidative stress and mitochondrial-mediated apoptotic cascade events in 6-OHDA-induced neurotoxicity in SH-SY5Y cells. We also investigated whether sulfuretin specifically acts by inhibiting phosphorylation of mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and glycogen synthase kinase-3beta (GSK-3β) as well as activation of the nuclear factor-κappa B (NF-κB) pathway. Sulfuretin significantly inhibited neuronal cell death, neurotoxicity, apoptosis, and reactive oxygen species (ROS) production. Sulfuretin also strikingly attenuated 6-OHDA-induced mitochondrial dysfunction. Moreover, sulfuretin significantly attenuated 6-OHDA-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase 1/2 (ERK 1/2) MAPKs, PI3K/Akt, and GSK-3β. Eventually, sulfuretin inhibited 6-OHDA-induced NF-κB translocation to the nucleus induced by 6-OHDA. The results of the current study provide the first evidence that sulfuretin protects SH-SY5Y cells against 6-OHDA-induced neuronal cell death, possibly through inhibition of phosphorylation of MAPK, PI3K/Akt, and GSK-3β, which leads to mitochondrial protection, NF-κB modulations and subsequent suppression of apoptosis via ROS-dependent pathways. Thus, we conclude that sulfuretin may have a potential role for neuroprotection and, therefore, may be used as a therapeutic agent for PD.
    Neurochemistry International 05/2014; · 2.66 Impact Factor