• 동의생리병리학회지
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• 제25권3호
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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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• 제19권1호
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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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• 제9권2호
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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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• 제56권9호
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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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• 제27권1호
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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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• 제15권4호
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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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• 제7권4호
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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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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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.

• 생명과학회지
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• 제12권3호
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• pp.332-339
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• 2002

옻나무(Rhus verniciflua Stokes)로부터 간섬유화에 따른 간독성의 경감기전을 추구할 목적으로 ethyl acetate 분획에서 분리한 fustin 및 sulfuretin을 실험동물에 투여하고서 혈액학적 변화 및 간장 중 활성산소에 미치는 영향 검토한 결과 담도결찰하여 간섬유화를 유도한 군에서는 AST, ALT, SDH, ${\gamma}$-GT활성 및 total bilirubin의 양이 현저히 증가되던 것이 옻나무의 메탄을 엑스(250 mg/kg), 에틸아세테이트 엑스(250 mg/kg), fustin(10 mg/kg) 및 sulfuretin(10 mg/kg)을 2주간 각각 경구투여 하므로서 유의성 있게 억제되었다. Hydroxyproline양 및 MDA 농도에서도 간섬유화를 유도하므로서 현저히 증가되던 것이 옻나무의 분획 및 sulfuretin과 fustin의 투여로서 각각 약 60% 및 47%정도 감소되었다. 간섬유화를 유도한 cytosolic계 효소인 xanthine oxidase 및 aldehyde oxidase의 활성이 현저히 증가되었으며 한편 superoxide dismutase, glutathione peroxidase 및 catalase은 간섬유화의 유도로 감소되었으나 옻나무의 분획(메탄올, 에틸아세테이트) 및 성분(fustin, sulfuretin)의 투여로서 조절되었다.

• 생명과학회지
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• 제13권6호
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• pp.775-781
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• 2003

옻나무(Rhus verniciflua Stokes)로부터 제초제인 paraquat(PQ)의 독성 경감기전을 추구할 목적으로 ethylacetate 분획에서 분리한 fustin 및 sulfuretin을 실험동물에 투여하고서 혈액학적 변화 및 간장 중 활성산소에 미치는 영향 검토한 결과 혈액 생화학적 인자 분석을 종합해 보면 옻나무의 메탄을 엑스(250 mg/kg), 에틸아세테이트 엑스(250 mg/kg), fustin(10 mg/kg) 및 sulfuretin(10 mg/kg)을 2주간 각각 경구투여 하고서 PQ를 투여하므로서 PQ의 독성이 유의성 있게 억제되었다. in vivo에서 옻나무의 분획 및 성분의 투여는 혈액생화학적 검사에서 PQ에 의해 유도된 간독성 지표인 s-GPT, s-GOT치, 신장독성지표인 BUN, creatinine치 및 조직손상의 지표인 ALP, MDA치를 억제하였다 폐조직중의 MDA함량, ALP활성 및 collagen함량도 억제하였다. 이로써 옻나무에는 PQ의 폐독성 및 각 장기의 독성을 효과적으로 경감시켜 줄 수 있는 물질이 함유되어 있는 것으로 사료된다.