• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.3
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• pp.533-539
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• 2011

Sulfuretin is one of the main flavonoids produced by Rhusverniciflua. Sulfuretin has been shown to exhibit many pharmacological activities including anti-oxidant, anti-obesity, anti-inflammatory and anti-mutagenic activities. However, the anti-skin photoaging effects of sulfuretin has not yet been reported. In the present study, we investigated the inhibitory effect of sulfuretin on the expression levels of MMP-1 and -3 in the human dermal fibroblast cells. Western blot analysis and real-time PCR revealed sulfuretin inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB-induced MAPK/NF-${\kappa}B$/p50 activation and MMP expression were completely blocked by pretreatment of sulfuretin. Taken together, sulfuretin could prevent UVB-induced MMP expressions through inhibition of MAPK/NF-${\kappa}B$/p50 activation.

• Natural Product Sciences
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• v.19 no.1
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• pp.54-60
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• 2013

Rhus verniciflua Stokes (Anacadiaceae) is a plant that is native to East Asian countries, such as Korea, China, and Japan, and it has been found to exert various biological activities including antioxidative, anti-aggregatory, anti-inflammatory, anti-mutagenic, and apoptotic effects. Sulfuretin is one of the major flavonoid component isolated from the heartwood of R. verniciflua. Reactive oxygen species (ROS), produced via dental adhesive bleaching agents and pulpal disease, can cause oxidative stress. In the present study, we isolated sulfuretin from R. verniciflua and demonstrated that sulfuretin possesses cytoprotective effects against hydrogen peroxide ($H_2O_2$)-induced dental cell death. $H_2O_2$ is a representative ROS and causes cell death through necrosis in human dental pulp (HDP) cells. $H_2O_2$-induced cytotoxicity and production of ROS were blocked in the presence of sulfuretin, and these effects were dose dependent. Sulfuretin also increased heme oxygenase-1 (HO-1) protein expression. In addition, to determine whether sulfuretin-induced HO-1 expression mediated this cytoprotective effect, HDP cells were cotreated with sulfuretin in the absence or presence of SnPP, an inhibitor of HO activity. Sulfuretin-dependent HO-1 expression was required for suppression of $H_2O_2$-induced HDP cell death and ROS generation. These results indicate that sulfuretin-dependent HO-1 expression was required for the inhibition of $H_2O_2$-induced cell death and ROS generation. In addition, sulfuretin may be used to prevent functional dental cell death and thus may be useful as a pulpal disease agent.

• Natural Product Sciences
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• v.9 no.2
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• pp.97-101
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• 2003

This study was undertaken to evaluate the antinociceptive and antiinflammatory effects of the heartwood extract of Rhus verniciflua (Anacardiaceae) and the two major components, sulfuretin and fustin. The MeOH extract, its EtOAc-soluble portion and sulfuretin showed significant antinociceptive activity in writhing and hot plate test assays and antiinflammaory effects in carrageenan-induced hind paw edema in rats. In particular, treatment of sulfuretin with 10 mg/kg dose (i.p.) reduced writhing frequency by 48.0% (p<0.01) compared to that of a control group. Further, the treatment of sulfuretin (5, 10 mg/kg, i.p.) for 7 days prevented the carrageenan-induced hind paw edema significantly (p<0.01). The antiinflammatory effect of sulfuretin was also confirmed by microscopic observation of mast cell numbers in muscle. In addition, sulfuretin suppressed the cyclooxygenase- 2 (COX-2) activity $(IC_{50}\;=\;28.7\;{\mu}M)$ in lipopolysaccharide-activated macrophage cells. This result indicates that the inhibitory effect of sulfuretin on COX-2 may be one of the antinociceptive/antiinflammatory mechanism.

• BMB Reports
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• v.56 no.9
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• pp.496-501
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• 2023

Elongation of most bones occur at the growth plate through endochondral ossification in postnatal mammals. The maturation of chondrocyte is a crucial factor in longitudinal bone growth, which is regulated by a complex network of paracrine and endocrine signaling pathways. Here, we show that a phytochemical sulfuretin can stimulate hypertrophic chondrocyte differentiation in vitro and in vivo. We found that sulfuretin stabilized nuclear factor (erythroid-derived 2)-like 2 (Nrf2), stimulated its transcriptional activity, and induced expression of its target genes. Sulfuretin treatment resulted in an increase in body length of zebrafish larvae and induced the expression of chondrocyte markers. Consistently, a clinically available Nrf2 activator, dimethyl fumarate (DMF), induced the expression of hypertrophic chondrocyte markers and increased the body length of zebrafish. Importantly, we found that chondrocyte gene expression in cell culture and skeletal growth in zebrafish stimulated by sulfuretin were significantly abrogated by Nrf2 depletion, suggesting that such stimulatory effects of sulfuretin were dependent on Nrf2, at least in part. Taken together, these data show that sulfuretin has a potential use as supporting ingredients for enhancing bone growth.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.107-116
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• 2019

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin's but not resveratrol's anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.

• Natural Product Sciences
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• v.15 no.4
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• pp.208-212
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• 2009

The heartwood of Rhus verniciflua Stokes (Anacardiaceae) is widely used for a medicinal plant to treat diabetes mellitus and lingering intoxication in the folkloric society of Korea, while the stem bark has been traditionally used to treat menstrual disorder and helminthiasis. We previously reported that a flavonoid, fustin, isolated from the heartwood of R. verniciflua is effective in Alzheimer‘s disease and rheumatoid arthritis. To explore the possibility to produce more flavonoid-rich fraction from this plant, the MeOH extracts from the plant parts of stem bark, outer heartwood, and inner heartwood were quantitatively analyzed by HPLC. Phenolic or flavonoid compounds (chlorogenic acid, caffeic acid, p-coumaric acid, sulfuretin, fustin, fisetin, luteolin and astragalin) were detectable in the HPLC chromatogram. The orange-colored inner heartwood was found to contain the highest levels of fustin (16.96 mg/g) and sulfuretin (2.22 mg/g). Moreover, the inner heartwood accumulated fustin and sulfuretin at least 4-fold higher level as compared to the stem bark and outer heartwood. The levels of total phenolic compounds positively correlated with the extents of antioxidant properties. Therefore, the inner heartwood of R. verniciflua could be used to increase fustin concentration of the extract which is capable of treating Alzheimer‘s disease and rheumatoid arthritis.

• Preventive Nutrition and Food Science
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• v.7 no.4
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• pp.347-352
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• 2002

The present study was undertaken to evaluate the anti-rheumatoidal arthritis effect of the R. verniciflua heartwood extract, its EtOAc fraction, and its primary flavonoids, sulfuretin and fustin. All test samples showed variably significant inhibitory effects on hind paw edema and trypsin inhibitor activity induced by Freund's complete adjuvant reagent (FCA reagent), and on vascular permeability caused by acetic acid. Treatment with 10 mg/kg (i.p.) sulfuretin for seven days inhibited edema formation by 54.2$\pm$3.0%. Test samples, especially sulfuretin, shifted the values of biochemical parameters such as serum-cholesterol, serum-triglyceride and serum-total protein toward the normal and restored the numbers of leucocytes and platelets. These results suggest that the heartwood of R. verniciflua reduces immunological injuries caused by FCA reagent provides evidence that suluretin is an active anti-rheumatoid arthritis agent.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.84-84
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• 2001

The heartwood of Rhus verniciflua has been known to be effective for lingering intoxication and diabetes mellitus and rheumatoidal arthritis in traditional folk medicine in Korea. We have previously reported that antimutagenic effect of flavonoids derived from the heartwood extract of R. verniciflua, and sulfuretin was the active component. Recently, we have demonstrated that sulfuretin could be an anti-inflammatory principle of the R. verniciflua heartwood partially dependent on cyclooxigenase-inhibitory activity. The present study was undertaken to demonstrate the anti-rheumatoidal arthritis effect of the R. verniciflua heartwood extract, its EtOAc fraction and the main flavonoids, sulfuretin and fustin. All the test samples showed variably significant inhibitory effects on hind paw edema induced by Freund's complete adjuvant reagent (FCA reagent). Sulfuretin treatment with 10 mg/kg (i.p.) for seven days showed the inhibitory effect of 54.2${\pm}$3.0%, Similar trends in RA- and CRP tests, vascular permeability test and trypsin inhibitor test were also found. In addition, no dead mouse was found even when the dose was increased up to 5,000 mg/kg (i.p.). Treatment with 250-1,500 mg/kg on normal rats did not show any marked toxicological significances in the tests of body weight gain, wet weight of organs and hepatic functions. These results suggested that the heartwood of R. verniciflua could be an adequate crude drug for rheumatoidal arthritis with an active component of sulfuretin. The toxicological safety of the heartwood of R, verniciflua is contrasted to known severe allergenic action of the stem bark or its exudate.

• Journal of Life Science
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• v.12 no.3
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• pp.332-339
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• 2002

The pathogenesis of cholestatic liver injury as well as the modulation of hepatic fibrogenesis is causally associated with involvement of reactive oxygen species and free radical reactions. In this study, we investigated whether flavonoids (fustin, sulfuretin) which were isolated from Rhus verniciflua Stokes (RCS) have antioxidant and antihepatotoxicity effect under the biliary liver fibrosis condition. After surgery (control) and posttreated RCS methanol extract (250mg/kg), ethyl acetate extract (250mg/kg) and flavonoids were administered p.o. 10mg/kg/day in two weeks for control groups. The concentration of clinical parameters and product of hepatic lipid peroxidation and the hydroxyproline content were significantly increased in liver fibrosis developed rats. Among the clinical parameters of serum, value of ALT, AST, SDH, total bilirubin and ${\gamma}$ -GT in posttreated RCS components-group showed significantly lower than in control-group. The content of hydroxyproline in posttreated RCS components-group showed lower than in control group and then the value of MDA in posttreated RCS components-group was also significantly reduced to 40~60% of that in control group. The hepatic xanthine oxidase and aldehyde oxidate activities were posttreated RCS components-group showed significantly lower than in control-group. The hepatic SOD and glutathione peroxidase activities were posttreated RCS components-group showed significantly higher than in control-group. Hence we concluded that active components of fustin and sulfuretin which were isolated from R. verniciflua Stokes were hepatoprotective effect in experimental liver fibrosis.

• Journal of Life Science
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• v.13 no.6
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• pp.775-781
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• 2003

In this study, we investigated to elevate the modulatory effect of flavonoid(fustin, sulfuretin, 10 mg/kg) which was isolated from Rhus verniciflua Stokes(RVS) in male Sprague-Dawley rats for 2 weeks on the toxicity of paraquat. In the flavonoids pretreated groups, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, blood urea nitrogen, creatinine, malondialdehyde and alkaline phosphatase activity in serum and malondialdehyde, alkaline phosphatase activity and collagen in lung tissue which was induced paraquat toxicity were slightly decrease compared to the normal group. In the lung tissue of flavonoids pretreated groups, malodialdehyde value, G-6-phosphatase activity and collagen synthesis were recovered to tile normal values and alkaline phosphatase activity was increased. From these results, we concluded that flavonoids which were isolated from RVS is an effective agent to inhibit the pulmonary and internal toxicities and hence we concluded that acitive components of fustin and sulfuretin which were isolated from RVS might be removed free radicals induced by paraquat.