Rhus Verniciflua Stokes Extract Research Articles

Evaluation of the Antifungal Effect of Rhus verniciflua Stokes Extract for Oral Application Potential.

Background and Objectives: This study confirms the possibility of using Rhus verniciflua Stokes (RVS) extract as a natural treatment for oral candidiasis. Materials and Methods: RVS was extracted with 70% ethanol to examine the antioxidant activity through polyphenol, flavonoid content, and DPPH (1,1-diphenyl-2-picrylhydrazyl). To evaluate the antifungal effect against Candida albicans (C. albicans; KCTC 7965/ATCC 10231) and evaluate the stability of RVS, a water-soluble tetrazolium salt (WST-1) assay was performed in human keratinocytes (HaCaT). Results: The findings revealed that RVS extract has fairly high antioxidant activity. The clear zones of the RVS extract against C. albicans increased in diameter due to the inhibition of fungal growth at higher concentrations. Treatment with the 1.25 mg/mL RVS extract had a more than 99% antifungal effect against C. albicans, and the 20 mg/mL RVS extract had a 100% antifungal effect. The WST-1 assay showed that the RVS extract induced low cell viability in the HaCaT cells, which inhibited their proliferation, and the RVS extract is also toxic to normal cells. Conclusions: Although the RVS extract with high antioxidant activity showed clear antifungal activity against C. albicans, it exhibited a low survival rate. Therefore, the development of a safe natural antibiotic is necessary.

Rhus Verniciflua Stokes Extract Suppresses Expression of Metalloproteinases, iNOS and COX-2 in THP-1 Cells Via Inhibiting NF-κB and MAPK Phosphorylation

Rhus Verniciflua Stokes Extract Suppresses Expression of Metalloproteinases, iNOS and COX-2 in THP-1 Cells Via Inhibiting NF-κB and MAPK Phosphorylation

Fermented Rhus Verniciflua Stokes Extract Alleviates Nonalcoholic Fatty Liver through the AMPK/SREBP1/PCSK9 Pathway in HFD-Induced Nonalcoholic Fatty Liver Animal Model

Background: We have previously reported the anti-hepatic lipogenic effect of fermented Rhus verniciflua stokes extract (FRVE) in an oleic-acid-treated HepG2 cell model. Methods: Herein, we advanced our understanding and evaluated the impact of FRVE in HFD-fed C57BL/6 mice using an animal model of nonalcoholic fatty liver disease (NAFLD). Milk thistle extract was used as a positive control to compare the effects of FRVE. Results: FRVE decreased body weight, intra-abdominal fat weight, and liver weight. Furthermore, FRVE decreased HFD-induced elevated serum levels of ALT, AST, TC, and TG, and downregulated the increase in hepatic lipid accumulation and TG levels. FRVE reduced hepatic SREBP-1, PCSK-9, SREBP-2, and ApoB mRNA levels. IHC data showed that FRVE reduced the levels of nucleic SREBP-1, increased the levels of LDLR, and upregulated the expression of p-AMPK. Conclusion: Overall, these results demonstrate the anti-hepatic lipidemic effect of FRVE in an animal model. These findings are consistent with our previous study and strongly suggest that FRVE exerts anti-hepatic lipogenic effects by activating AMPK.

Rhus verniciflua Stokes extract suppresses migration and invasion in human gastric adenocarcinoma AGS cells.

BACKGROUND/OBJECTIVESMany studies have suggested that Rhus verniciflua Stokes (RVS) and its extract are anticancer agents. However, RVS had limited use because it contains urushiol, an allergenic toxin. By improving an existing allergen-removal extraction method, we developed a new allergen-free Rhus verniciflua Stokes extract (RVSE) with higher flavonoid content. In this study, we examined whether RVSE inhibits the ability of AGS gastric cancer cells to migrate and invade.MATERIALS/METHODSThe flavonoids content of RVSE was analyzed by HPLC. The effects of RVSE on migration and invasion in AGS cells were analyzed by each assay kit. Matrix metalloproteinase (MMP)-9, plasminogen activator inhibitor-1 (PAI-1) and urokinase-type plasminogen activator (uPA) protein expression was analyzed by protein antibody array. The Phosphorylation of signal transducer and activator of transcription (STAT) 3 were assayed by Western blot analysis.RESULTSRVSE treatment with 0–100 μg/mL dose-dependently reduced the ability of AGS cells to migrate and invade. Notably, treatment with RVSE strongly inhibited the expression of MMP-9 and uPA and the phosphorylation of STAT3. In contrast, RVSE treatment dramatically increased the expression of PAI-1. These results indicate that the inhibition of MMP-9 and uPA expression and STAT3 phosphorylation and the stimulation of PAI-1 expression contributed to the decreased migration and invasion of AGS cells treated with RVSE.CONCLUSIONSThese results suggest that RVSE may be used as a natural herbal agent to reduce gastric cancer metastasis.

Extract of Rhus verniciflua Stokes Induces p53-Mediated Apoptosis in MCF-7 Breast Cancer Cells.

Rhus verniciflua Stokes has long been used as a food supplement and traditional herbal medicine for various ailments in East Asia. We evaluated the anticancer effects of Rhus verniciflua Stokes extract (RVSE) on MCF-7 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, annexin V/7-AAD staining, and western blotting. In addition, the gallic acid content of RVSE was assayed using high-performance liquid chromatography. RVSE inhibited the growth of MCF-7 cells in a dose-dependent manner by inducing apoptosis in the sub-G1 phase. RVSE also significantly increased the number of apoptotic cells and increased the expression of p53 and p21 in a dose-dependent manner. Furthermore, RVSE treatment increased the Bax:Bcl-2 ratio and the levels of apoptosis-related factors, such as cleaved caspase-3 and -9 and PARP, in MCF-7 cells. Our findings suggest that the proapoptotic effect of RVSE on MCF-7 cells is mediated by p53, p21, and the intrinsic mitochondrial cascade. Thus, RVSE shows promise for the prevention and treatment of breast cancer.

Macrophages from Mice Administered Rhus verniciflua Stokes Extract Show Selective Anti-Inflammatory Activity.

The bark of Rhus verniciflua Stokes (RVS) is used as a food additive and herbal medicine for various inflammatory disorders and cancer in Eastern Asia. RVS has been shown to exert anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated macrophages in vitro, but whether oral administration of RVS affects the inflammatory response of macrophage needs to be verified. RVS was given orally to mice for ten days. For isolation of macrophages, intraperitoneal injection of thioglycollate was performed. For determination of serum inflammatory response, intraperitoneal injection of LPS was applied. RVS stimulated monocyte differentiation in thioglycollate-induced peritonitis by increasing the population of cells expressing CD11b and class A scavenger receptors. These monocyte-derived macrophages showed an increased uptake of acetylated low-density lipoprotein. When peritoneal macrophages from the RVS group were stimulated with LPS, the levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the supernatant decreased, but the level of IL-12 increased. The surface expression of CD86 was reduced, but surface expression of class II major histocompatibility complex molecules was increased. RVS suppressed the serum levels of LPS-induced TNF-α and IL-6. Collectively, RVS promoted monocyte differentiation upon inflammatory insults and conferred selective anti-inflammatory activity without causing overall inhibitory effects on immune cells.

Antimicrobial activity and active compounds of a Rhus verniciflua Stokes extract.

The Rhus verniciflua Stokes (RVS) extract is used as a traditional herbal medicine in Southeast Asian countries such as Korea and China. In the present study, one phenolic acid and six flavonoids were isolated from an 80% ethanol RVS extract to examine their antimicrobial activities. These compounds were identified as 3',4',7-trihydroxyflavone (1), methyl gallate (2), gallic acid (3), fusti (4), fisetin (5), butin (6), and sulfuretin (7) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nuclear magnetic resonance spectroscopy. The antimicrobial activities of compounds 5 and 6 (at a dose of 16 μg/mL each) were superior to that of the control, cycloheximide (at a dose of 25 μg/mL), against Hypocrea nigricans; additionally, the activities of compounds 1 and 2 (at a dose of 8 μg/mL each) were superior to the control against Penicillium oxalicum. Also, chemical compounds 1 and 5 (at a dose of 16 μg/mL each) had higher activities than the control (25 μg/mL) against Trichoderma virens. Chemical compound 1 (at a dose of 8 μg/mL) had a similar activity to that of the control against Bacillus subtilis. The obtained results suggest that the RVS extract could be a promising food and nutraceutical source because of the antimicrobial properties of its phenolic compounds.

Potential Efficacy of Allergen Removed Rhus Verniciflua Stokes Extract to Maintain Progression-Free Survival of Patients With Advanced Hepatobiliary Cancer

Hepatobiliary cancers are among the leading causes of cancer-related deaths worldwide. Most of the early-stage, surgically resectable cases show recurrence, and when they do, the prognosis is dismal with limited available treatment options. Here, we report three patients with relapsed hepatobiliary cancers who presented relatively long progression-free survival with the administration of a natural product, allergen removed Rhus verniciflua Stokes (RVS) extract. After commencement of RVS extract, they were progression-free for over 56 months in one case of recurred cholangiocarcinoma, and for over 16 and 114 months respectively, in two cases of advanced hepatocellular carcinoma. These cases suggest that the RVS extract could be a potential alternative for advanced hepatobiliary cancer that has no other available treatment.

Rhus verniciflua Stokes extract induces inhibition of cell growth and apoptosis in human chronic myelogenous leukemia K562 cells.

Rhus verniciflua Stokes has been widely used as a traditional medicinal plant with a variety of pharmacological activities. We investigated the mechanisms involved in mediating the effects of Rhus verniciflua Strokes (R.verniciflua) extract in human chronic myelogenous leukemia K562 cells, including caspase-dependent apoptotic pathways related to cell-cycle arrest, as well as the inhibition of nuclear factor NF-κB activation and upregulation of the mitogen-activated protein kinase (MAPK) signaling pathway. R.verniciflua extract suppressed the abnormal cellular proliferation of K562 cells in a dose- and time‑dependent manner and increased the quantitative proportions of cells involved in the early and late process of apoptosis. Furthermore, R.verniciflua extract significantly mediated the mRNA levels of pro-apoptotic and anti-apoptotic regulators, such as Bcl-2, Bax, Mcl-1 and survivin in apoptotic cells. Particularly, the treatment of K562 cells with R.verniciflua extract augmented the caspase‑3 activity and increased the expression of caspase‑3 protein, while co-treatment with R.verniciflua extract and the permeant pan‑caspase inhibitor Z-VAD-FMK and caspase‑3 inhibitor Z-DEVD-FMK inversely enhanced the proliferation of K562 cells. The extract of R.verniciflua inhibited the activation of NF-κB and the phosphorylation of ERK. Collectively, these results indicated that the extract of R.verniciflua inhibited the proliferation of human chronic myelogenous leukemia K562 cells by activating the apoptotic process via caspase‑3 overexpression and the regulation of the NF-κB and MAPK signaling.

Sulfuretin has therapeutic activity against acquired lymphedema by reducing adipogenesis

Acquired lymphedema is a pathological condition associated with lymphatic dysfunction caused by surgical treatments for cancer. Although global estimates of the prevalence of acquired lymphedema have been rising, there are currently no effective therapeutics available. Since adipose tissue accumulation is a clinical hallmark of lymphedema, we hypothesized that regulation of adipogenesis in lymphedematous tissue could be used as a therapeutic intervention against lymphedema. Toward this, we investigated the possibility of anti-adipogenic 30% ethanol Rhus verniciflua Stokes (RVS) extract as a potential lymphedema treatment. Oral administration of RVS extract ameliorated volumetric symptoms of lymphedema in a mouse model. RVS administration also reduced adipose tissue accumulation in lymphedematous tissue and downregulated expression of adipocyte markers, including Pparγ and Fabp4. Sulfuretin was identified as a major bioactive compound in the 30% ethanol RVS extract in liquid chromatography-mass spectrometry analysis. Similar to the activities of RVS, sulfuretin inhibited adipocyte differentiation in 3T3-L1 preadipocytes. Moreover, treatment with sulfuretin on lymphedema-induced mice reduced lymphedema volume, decreased the expression of adipogenic markers, but induced the expression of markers associated with lymphangiogenesis. Taken together, our data raise the possibility that sulfuretin might be used in therapeutic interventions against acquired lymphedema.

Rhus verniciflua Stokes Extract and Its Flavonoids Protect PC-12 Cells against H2O2-Induced Cytotoxicity.

Rhus verniciflua Stokes (RVS), an herbal medicine found in East Asia, was extracted and further fractionated to investigate its antioxidant capacity and neuroprotective effects. The RVS ethyl acetate (EtOAc) fraction had the highest level of total phenolics and antioxidant capacity among all solvent fractions tested. Pretreatment of PC-12 cells with the EtOAc fraction effectively attenuated H2O2-induced oxidative damage. Furthermore, the EtOAc fraction significantly attenuated caspase-3 activity, resulting in inhibition of H2O2-induced apoptosis. We identified and quantified fustin, sulfuretin, and butein in the EtOAc fraction using accurate mass quadrupole time-of-flight mass spectrometry and reversed-phase high-performance liquid chromatography. The intracellular antioxidant capacity and superoxide dismutase (SOD) activity were significantly increased in PC-12 cells treated with the EtOAc fraction and with individual flavonoids. When cells were pretreated with the EtOAc fraction or individual flavonoids and then co-incubated with diethyldithiocarbamic acid (an inhibitor of SOD activity), cell viability against H2O2-induced oxidative stress was attenuated. These results suggest that the RVS EtOAc fraction and its flavonoid constituents protect PC-12 cells against H2O2-induced neurotoxicity through their antioxidant properties.

Effects of Fermented Rhus Verniciflua Stokes Extract on Diet-induced Hyperlipidemia in Rats

This study was designed to investigate the antihyperlipidemic activity of Fermented Rhus Verniciflua Stokes Extract(FRVSE) on diet-induced hyperlipidemia in rats. The animals were divided into 4 groups of the normal group(fed with normal diet), control group(fed with high fat diet), sample A group(fed with high fat diet and medicated FRVSE 192 ㎎/㎏/day), sample B group(fed with high fat diet and medicated FRVSE 384 ㎎/㎏/day), and received oral administration of each prescription with diet for a period of six weeks. The changes in the body weight, the liver weight, the epididymal fat weight, and the plasma levels of total cholesterol, triglyceride(TG), high density lipoprotein(HDL) cholesterol and low density lipoprotein(LDL) cholesterol were measured. In sample A group, the weight of liver and plasma level of TG decreased significantly. There was a significant decrease in the plasma level of total cholesterol, TG and LDL cholesterol in the sample B group. These results suggest that the FRVSE have a good antihyperlipidemic activity and a potential to treat hyperlipidemia.

A Standardized Extract of Rhus verniciflua Stokes Protects Wistar Rats Against Lipopolysaccharide-Induced Acute Inflammation.

Rhus verniciflua stokes (RVS) (Anacardiaceae) has been traditionally used as a folk remedy for gastritis, several cancers, and various metabolic diseases. The present study evaluated the anti-inflammatory effect of RVS extract standardized to fustin content using lipopolysaccharide (LPS)-stimulated rats. The rats were randomly divided into six groups and intragastrically administered 0, 100, 250, or 500 mg/kg body weight (bw) of RVS or 15 mg/kg bw of fustin for 14 days. LPS was intraperitoneally injected 18 h before sacrifice. The nitric oxide levels of RVS extract in either the serum or liver were significantly decreased compared to the LPS-treated rats (P<.05). The treatment with the RVS extract also blunted the rise of malondialdehyde levels in the liver (P<.05). The administration of RVS extract and fustin significantly prevented the elevation of interleukin 6 cytokine, iNOS, and COX-2 mRNA expression in the liver. Inflammatory cell infiltration was also significantly attenuated by the RVS extract or fustin supplementation. These results suggest that our standardized RVS extract has preventive effects on inflammatory reactions.

Anti-inflammatory effect of Rhus verniciflua stokes extract in the murine macrophage cell line, Raw264.7

Rhus verniciflua stokes (RVS) (Anacardiaceae), which contains the major flavonoids fustin, fisetin, and sulfuretin, is known to have anti-inflammatory effects. Using lipopolysaccharide (LPS)—induced RAW264.7 cells, we examined which flavonoids were the most active compounds in the RVS extract. RVS extract dose-dependently reduced the production of nitric oxide, prostaglandin E2, interleukin-6 (IL-6), and reactive oxygen species (ROS) induced by LPS. Only sulfuretin significantly suppressed IL-6 and ROS levels although the effects were smaller than those provided by the RVS extract at the equivalent concentration (0.25 µg/mL of pure sulfuretin and 100 µg/mL of RVS extract). Other flavonoids such as fisetin and fustin did not show anti-inflammatory effects at the levels typically contained in the RVS extract. Taken together, sulfuretin was postulated to be the major anti-inflammatory flavonoid in RVS extract.

Extract of Rhus verniciflua stokes protects the diet-induced hyperlipidemia in mice.

Rhus verniciflua stokes (RVS) is a popular medicinal plant in oriental medicines which is commonly used to resolve extravasated blood. To elucidate the molecular mechanism of the role of RVS extracts on the regulation of lipid and cholesterol biosynthesis, we investigated whether RVS extract protect the hyperlipidemia in western diet-induced C57BL6/J mice. Mice fed a western diet and additionally RVS extracts was administered orally at a dose of 0.1 or 1g/kg/day for 2weeks respectively. Group with higher dose of RVS extract showed a significantly decreased body weight compared with western diet fed mice groups. And total cholesterol, LDL-cholesterol levels and fatty liver formation were also improved especially in group of mice fed western diet supplemented high dose RVS extracts. Next, synthesis of hepatic bile acids were significantly increased in RVS extract fed groups. Furthermore, RVS extracts significantly increase promoter activity of Cyp7a1 via up-regulate the transcriptional expression level of LXRα. Our data suggest that RVS extracts could be a potent therapeutic ingredient for prevent a hyperlipidemia via increase of bile acids biosynthesis.

Successful Outcome of Elderly Patients with Advanced Malignant Melanoma by Standardized Allergen-removed Rhus verniciflua Stokes Extract and Bojungikki-tang: Two Cases

Objectives: Advanced malignant melanoma (MM) has a poor prognosis, with an expected 2-year survival rate of 10 to 20%. It has long been recognized as an immunogenic tumor, and is worse for elderly patients. Many studies have suggested that herbal treatments improve immune functions, but few clinical studies have reported on this topic. Patients and History: We present two cases of female patients (72 and 77 years old, respectively) with advanced MM. The 72-year-old female patient was, at first, diagnosed with MM with multiple bone metastases. She received resection of the primary lesion, but refused further chemotherapy. The 77-year-old female patient was diagnosed with cutaneous MM of the left heel, with suspicion of sentinel node lymphadenopathy; however, she also refused any conventional treatment due to old age. Course of Therapy and Results: Both patients were exclusively treated with standardized allergen-removed Rhus verniciflua stokes (aRVS) extract combined with Bojungikki-tang (BT, Bu-Zhong-Yi-Qi-Tang in Chinese or Hochu-ekki-to in Japanese). Both patients are still alive and doing well (Feb. 2014), demonstrating that the 72-year-old patient has lived for 27 months and the 77-year-old patient has lived for 31 months without disease progression since the aRVS and BT administration. Conclusion: We suggest that the combination of aRVS extract and BT could be a candidate for overcoming the cancer’s immunoediting process especially for elderly MM patients intolerant of conventional treatment.

Standardized Rhus verniciflua stokes extract and its major flavonoid fustin attenuate oxidative stress induced by tert-butyl hydroperoxide via activation of nuclear factor erythroid 2-related factor

The antioxidant effects of an urushiol-free standardized Rhus verniciflua Stokes (RVS) extract and fustin were investigated using oxidative stress-induced rats by tert-butyl hydroperoxide (t-BHP). Hepatic glutathione levels were higher in RVS and fustin groups than those of the t-BHP treated control group. The level of hepatic nuclear factor erythroid 2-related factor was increased by RVS and fustin. The histology results indicated that rats fed RVS had a lower rate of necrosis than the control rats injected with t-BHP.

옻나무 추출물의 침지가 가스조절포장으로 저장한 한우고기 스테이크의 총환원력, 단백질산화 및 육색소산화에 미치는 영향

The objective of this research was to investigate the effect of immersion in Rhus verniciflua Stokes extract (RVSE) on the total reducing ability (TRA), protein oxidation and myoglobin oxidation of beef steak (Hanwoo longissimus muscle) stored with high oxygen-modified-atmosphere packaging (MAP) (HOMAP, 75% +20% +5% ) and low oxygen-MAP (LOMAP, 0% +20% +80% ) at for nine days. RVSE induced TRA (p value but reduced the carbonyl content and R630-R580, as an index of the intensity of redness by oxymyoglobin, and the CIE ,, and values. HOMAP maintained a lower TRA, MetMb concentration, and CIE value but had higher R630-R580 and CIE , , and values compared to LOMAP. Therefore, RVSE induced TRA and protein oxidation stability but reduced myoglobin stability in Hanwoo beef steak. In addition, the effects of HOMAP were opposite those of RVSE.

Efficacy and Safety of Standardized Allergen-Removed Rhus verniciflua Stokes Extract in Patients with Advanced or Metastatic Pancreatic Cancer: A Korean Single-Center Experience

Background: Pancreatic cancer has the worst prognosis because of poor response to conventional therapy. We investigated the clinical feasibility of the standardized allergen-removed Rhus verniciflua Stokes (aRVS) extract as a potential therapeutic agent for advanced or metastatic pancreatic cancer. Patients and Methods: From July 2006 to June 2010, patients with advanced or metastatic pancreatic adenocarcinoma were checked in our institution. After applying inclusion/exclusion criteria, 42 patients were eligible for the final analysis. Overall survival, clinical benefit and adverse events of these patients treated with aRVS in the aftercare period were determined. Results: In May 2011, 39 patients had died and the remaining 3 patients were alive with evidence of disease. The mean RVS administration period was 3.86 months (95% confidence interval 2.52–5.20). The median overall survival for the entire population was 7.87 months (95% confidence interval 5.14–10.59), and the 1-year survival rate was 26.2%, which is compatible with external controls. Using univariate and multivariate analyses, aRVS treatment including performance status and prognostic index significantly affected overall survival. A clinical benefit response was also shown by aRVS treatment which was not dependent on concurrent chemotherapy. Adverse reactions to aRVS treatment were mostly mild and self-limiting. Conclusions: The standardized aRVS extract might be beneficial for patients with advanced or metastatic pancreatic cancer since it positively affected overall survival and clinical symptoms without significant adverse effects.

Leaf extract ofRhus vernicifluaStokes protects dopaminergic neuronal cells in a rotenone model of Parkinson's disease

The present study investigated the neuroprotective effects of Rhus verniciflua Stokes (RVS) leaf extract on rotenone-induced apoptosis in human dopaminergic cells, SH-SY5Y. Cells were pretreated with RVS extract for 1 h then treated with vehicle or rotenone for 24 h. Cell viability, cell cytotoxicity, cell morphology and nuclear morphology were examined by MTT assay, lactate dehydrogenase release assay, phase contrast microscopy and staining with Hoechast 33342, respectively. Reactive oxygen species were measured by 2'7'-dichlorofluorescein diacetate and fragmented DNA was observed by TUNEL assay. Mitochondrial membrane potential was determined by Rhodamine 123. Pro-apoptotic and anti-apoptotic proteins and tyrosine hydroxylase were analysed by Western blotting. Results showed that RVS suppressed rotenone-induced reactive oxygen species generation, cellular injury and apoptotic cell death. RVS also prevented rotenone-mediated changes in Bax/Bcl-2 levels, mitochondrial membrane potential dissipation and Caspase 3 activation. Moreover, RVS pretreatment increased the tyrosine hydroxylase levels in SH-SY5Y cells. These findings demonstrate that RVS protects SH-SY5Y cells against rotenone-induced injury and suggest that RVS may have potential therapeutic value for neurodegenerative disease associated with oxidative stress.