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Sulfuretin is a natural flavonoid found in the plant Rhus verniciflua STOKES. The plant has been traditionally used as medicinal agent for antiviral, cathartic, diaphoretic, anti-rheumatic and sedative activities in East Asia. In this study we isolated and identified sulfuretin from R. verniciflua and investigated its anti-adipogenic activity against 3T3-L1 preadipocytes cells. We evaluated the effects of sulfuretin on the adipogenic transcription factors like peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid synthase (FAS), Fabp4, adiponectin and zinc fingerprint protein (Zfp) 521 by gene expression (real-time QPCR) and Western blot analysis. Sulfuretin treatment at Day 0 and 2 showed significant reduction of lipid production in 3T3-L1 cells in concentration dependent manner. Gene expression analysis (real-time PCR) revealed that sulfuretin inhibited the both major adipogenic factors (C/EBPα, C/EBPβ and PPARγ) and minor adipogenic factors (sterol regulatory element-binding protein (SREBP1c), adiponectin, FAS, Fabp4, Zfp423, and Ebf1). Western blot analysis showed the increased expression of β-catenin and suppression of PPARγ after sulfuretin treatment. Overall, sulfuretin is a natural flavonoid having potent anti-adipogenic activity through the suppression of major adipogenic factors C/EBPα, C/EBPβ and PPARγ, which initiate adipogenesis.

Rhus verniciflua STOKES (RVS) is used as an anti-cancer agent in traditional herbal medicine. However, the underlying molecular mechanism of its action is poorly understood. Here, we elucidated the mechanism of the anti-cancer mechanism of RVS in MCF-7 human breast cancer cells. We found that RVS increased the phosphorylation of AMP-activated protein kinase (AMPK) and downstream acetyl-CoA carboxylase (ACC) and suppressed cell viability in an AMPK-dependent fashion. RVS also induced an increase in reactive oxygen species (ROS) levels. RVS-induced AMPK phosphorylation was not observed in the presence of N-acetyl-cysteine (NAC), which indicated that ROS is associated with RVS-induced AMPK phosphorylation. In addition, fluorescent staining (Annexin V/propidium iodide) revealed that RVS increased the expression of Annexin V, which indicates that RVS leads to cancer-induced apoptosis. Moreover, RVS increased the phosphorylation of p53 and the expression of Bax. The inhibition of AMPK blocked RVS-induced p53 phosphorylation and Bax expression, which suggests that AMPK is involved in RVS-induced cancer apoptosis. Taken together, these results demonstrate that RVS has anti-tumor effects on MCF-7 cells through an AMPK-signaling pathway.

In the present study, extracts from Rhus verniciflua were demonstrated to significantly attenuate the negative effects of hydrogen peroxide (H(2)O(2)) on transformed retinal ganglion cell line (RGC-5 cells), indicating that they may be protective against oxidative stress-induced retinal degeneration. The inclusion of R. verniciflua in the culture was found to both reduce the levels of reactive oxygen species (ROS) present and lessen the up-regulation of apoptotic proteins such as cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, and cleaved caspase-9. Active compounds were also successfully isolated from R. verniciflua using high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3.5:5:3.5:5, v/v). Using this method, we successfully separated 252.1 mg of fustin at a purity of over 93.09%, 51.2 mg of fisetin at a purity of over 95.45%, 39.7 mg of sulfuretin at a purity of over 95.17%, and 10.7 mg of butein at a purity of over 95.01% from 1.5 g of R. verniciflua extract. The chemical structures of these compounds were elucidated by chemical and spectral analyses. There isolated compounds also significantly attenuated the negative effects of H(2)O(2) on RGC-5 cells. Results therefore suggest that, due to its anti-oxidative and anti-apoptotic effects, R. verniciflua could be used as a lead substance for the treatment of retinal diseases such as glaucoma.

Butein (3,4,2',4'-tetrahydroxychalcone), a plant polyphenol, is a major component in isolate of Rhus verniciflua STOKES (Anacardiaceae). It is shown to exert various potent effects such as antioxidant, antiinflammatory induction of apoptosis among many properties. In this study, we investigated the effect of butein on cytokine-induced β-cell damage. Pre-treatment with butein is shown to increase the viability of cytokine-treated INS-1 cells at concentrations of 15-30 µM. Butein prevented cytokine-mediated cell death, as well as nitric oxide (NO) production, and these effects correlated well with reduced levels of protein expression of the inducible nitric oxide synthase (iNOS). Furthermore, the molecular mechanisms by which butein inhibits iNOS gene expression appeared to be through the inhibition of nuclear factor-κB (NF-κB) translocation. In a second set of experiments, rat islets were used to demonstrate the protective effects of butein and the results were essentially the same as those observed in Beutin pretreated INS-1 cells. Butein prevented cytokine-induced NO production, iNOS expression, and NF-κB translocation and inhibition of glucose-stimulated insulin secretion (GSIS). In conclusion, these results suggest that butein can be used for the prevention of functional β-cell damage and preventing the progression of Type 1 diabetes mellitus (T1DM).

Nowadays herbal medicines of skin-whitening cosmetics are popular with women. We attempted to find the whitening activity compounds present in many herbal medicines used for this purpose and discuss their mechanisms in melanin biosynthesis. The 70% acetone extracts of 10 kinds of herbs were investigated for their mushroom tyrosinase activity inhibition. Among these 10 extracts, Chinese galls showed inhibitory activity against tyrosinase, with a 50% inhibitory concentration (IC(50)) value of 22 microg/ml. In a B16 mouse melanoma cell culture assay, Chinese galls dose-dependently inhibited melanin biosynthesis. Using ultraviolet A (UVA) or alpha-melanocyte-stimulating hormone (alpha-MSH) to stimulate B16 cells after Chinese gall treatment, the melanin biosynthesis of B16 cells was inhibited in a dose-dependent manner. The active compounds of Chinese galls were isolated by column chromatography, and the melanin biosynthesis inhibition in B16 melanoma cells was measured. Three gallotannins, 2,3,4,6-tetra-O-galloyl-D-glucopyranose, 1,2,3,6-tetra-O-galloyl-beta-D-glucopyranose, and 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose, were isolated from Chinese gall extract, and their IC(50) values of tyrosinase inhibition activity were 54, 30, and 15 muM, respectively. By the mushroom tyrosinase inhibition kinetics assay, the three gallotannins were all determined to be non-competitive inhibitors. These results indicated that Chinese galls inhibit melanin biosynthesis, associated with hyperpigmentation and can be used as skin-whitening cosmetics for skin care.

The aim of this paper was to evaluate active principles for diabetic complications from Rhus verniciflua. Nine compounds were isolated via bioactivity guided fractionation and isolation and tested for their effects on recombinant human aldose reductase and advanced glycation endproducts. Butein and sulfuretin isolated from ethyl acetate fraction were found to possess strongly both forms of aldose reductase and advanced glycation endproducts inhibition. The inhibitory activity of butein against a recombinant human aldose reductase (IC(50) value: 0.5 microM) was 2.6 times more potent that of epalrestat as a positive control (IC(50) value: 1.3 microM). The inhibitory potency of sulfuretin (IC(50) value: 124.7 microM) on advanced glycation end-products was about 10 times more potent that of aminoguanidine as a positive control (IC(50) value: 1231.0 microM). These compounds all displayed antioxidative activity which was measured by Photochem apparatus. It was concluded, therefore, butein and sulfuretin have antioxidative as well as aldose reductase and advanced glycation endproducts inhibitory effects. As a result, these compounds could be proposed as a leading compound for further study as a new natural products drug that could be used for diabetic complications.

Rhus verniciflua Stokes (RVS) has traditionally been used for medical purpose, such as healing of inflammatory diseases in South Korea. Glycoprotein (36 kDa) was isolated from RVS fruit, purified and used to evaluate the inhibitory effect on inflammatory-related proteins and nitric oxide (NO) production in lipopolysaccharide (LPS, 200 ng/ml)-stimulated RAW 264.7 (murine macrophage cell line). Our results were showed that RVS glycoprotein has a strong antioxidative activity against lipid peroxyl radicals in cell-free system, and inhibits NO production in LPS-stimulated RAW 264.7 cells. To elucidate the inhibitory effect of RVS glycoprotein on activities of inflammatory-related proteins, we firstly evaluated the amount of intracellular reactive oxygen species (ROS), and expression of intracellular protein kinase C (PKC), nuclear factor (NF)-kappaB, and activator protein-1 (AP-1). The results in the present study showed that RVS glycoprotein (200 microg/ml) inhibits ROS production and PKCalpha translocation, and down-regulates the expression of NF-kappaB and AP-1. Such upstream signals consequently inhibited the levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 expression. Therefore, we speculate that RVS glycoprotein inhibits the inflammatory-related protein and can act as an anti-inflammatory agent.

The goal of this study was to determine the effects of Rhus verniciflua stokes (RVS) on the radical scavenging activities and H2O2-induced cytotoxicity in macrophage 264.7 cells. An 80% ethanol extract of RVS was purified by ion exchange chromatography (IEC). Purified RVS extract contained a high amount of phenolics (55.5 g/100 g of extract) and flavonoids (5.9 g/100 g of extract) and its antioxidant activities, such as DPPH, superoxide anion and hydroxyl radical scavenging activities, was higher than the unpurified RVS extract. Purified RVS extract significantly reduced intracellular ROS formation caused by H2O2. Purified RVS extract also prevented the cell death of macrophage RAW 264.7 cells induced by H2O2. Interestingly, co-treated purified RVS extract effectively reduced thiobarbituric acid reactive substance (TBARS) formation, and attenuated catalase depletion at concentration of 100 microg/ml (p<0.05). Study using PDA-HPLC analyses have found that the purified RVS extract contains six major low molecular compounds as p-coumaric acid, fustin, kaempferol-3-O-glucoside, sulfuretin, butein and kaempferol. These results indicate that purified RVS extract, tested in this study, could contribute to the antioxidant activities and inhibition of intracellular ROS level.