• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.214.2-214.2
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• 2003

Eupatilin (5,7-dihydroxy-3",4",6-trimethoxyflavone) is an active ingredient of an ethanol extract of Artemisia asiatica (DA-9601) that is used in the treatment of gastritis. In vitro and in vivo metabolism of eupatilin in the rats has been studied by LC- electrospray mass spectrometry. Rat liver microsomal incubation of eupatilin in the presence of NADPH and UDPGA resulted in the formation of four metabolites (M1-M4). M1, M2, M3 and M4 were tentatively identified as 3"- or- 4"-O-demethyl-eupatilin glucuronide, eupatilin glucuronide, 6-O-demethyleupatilin and 3"-or 4"-O-demethyl- eupatilin glucuronide, eupatilin glucuronide, 6-O-demethyleupatilin and 3"-or 4"-O- demethyl-eupatilin glucuronide, eupatilin glucuronide, 6-O demethyleupatilin and 3"-or 4"-O-demethyl-eupatilin glucuronide, respectively. (omitted)

• Journal of Gastric Cancer
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• 제11권1호
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• pp.16-22
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• 2011

Purpose: Eupatilin is an antioxidative flavone and a phytopharmaceutical derived from Artemisia asiatica. It has been reported to possess anti-tumor activity in some types of cancer including gastric cancer. Eupatilin may modulate the angiogenesis pathway which is part of anti-inflammatory effect demonstrated in gastric mucosal injury models. Here we investigated the anti-tumor effects of eupatilin on gastric cancer cells and elucidated the potential underlying mechanism whereby eupatilin suppresses angiogenesis and tumor growth. Materials and Methods: The impact of eupatilin on the expression of angiogenesis pathway proteins was assessed using western blots in MKN45 cells. Using a chromatin immunoprecipitation assay, we tested whether eupatilin affects the recruitment of signal transducer and activator of transcription 3 (STAT3), aryl hydrocarbon receptor nuclear translocator (ARNT) and hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) to the human VEGF promoter. To investigate the effect of eupatilin on vasculogenesis, tube formation assays were conducted using human umbilical vein endothelial cells (HUVECs). The effect of eupatilin on tumor suppression in mouse xenografts was assessed. Results: Eupatilin significantly reduced VEGF, ARNT and STAT3 expression prominently under hypoxic conditions. The recruitment of STAT3, ARNT and HIF-$1{\alpha}$ to the VEGF promoter was inhibited by eupatilin treatment. HUVECs produced much foreshortened and severely broken tubes with eupatilin treatment. In addition, eupatilin effectively reduced tumor growth in a mouse xenograft model. Conclusions: Our results indicate that eupatilin inhibits angiogenesis in gastric cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of gastric cancer.

• Biomolecules & Therapeutics
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• 제11권3호
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• pp.163-168
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• 2003

Pharmacokinetics of eupatilin (an active components of $Stillen^{\circledR}$, a new antigastritic agent) were investigated after both intravenous and oral administration at a dose of 30mg/kg to rats. After intravenous administration, the plasma concentrations of unchanged eupatilin declined rapidly with a mean terminal half-life of 0.101 h. Eupatilin was eliminated fast in rats; the total body clearance was 121 mL/min/kg. Eupatilin was mainly metabolized in rats; the percentage of intravenous dose of eupatilin excreted in 24 h urine and feces as unchanged eupatilin was only 2.5 and 0.919％, respectively. Eupatilin was mainly metabolized to form its glucuronide conjugate; after intravenous administration, 15.9 and 51.7％ of intravenous dose was excreted in 24 h urine and feces, respectively, as eupatilin plus its glucuronide. After oral administration, the absolute bioavailability was only 3.86％ based on $AUC_{0-24h}$ of eupatilin plus its glucuronide. Approximately 68.5％ of oral dose was not absorbed from the entire gastrointestinal tract. Therefore, it could be concluded that the superior effect of eupatilin in experimental animal models of gastric ulcer and inflammatory bowel disease after oral administration could be due to the local action of eupatilin. Further pharmacokinetic studies to elucidate the local action of eupatilin are required.

• 한국작물학회지
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• 제50권spc1호
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• pp.204-207
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• 2005

본 연구는 최근 다양한 기능이 보고된 쑥의 eupatilin성분과 jaceosidin 성분 고함유 유전자원을 선발하고 기능성 작물로서의 개발가능성을 제시하고자 실험을 실시하고 그 결과를 요약하면 다음과 같다. 1. 12개 지역의 도서벽지에서 수집한 자생쑥을 분석한 결과 강화${\cdot}$백령도 지역의 수집 쑥에서 eupatilin과 jaceosidin함량이 높았다. 그 중 가장 높은 것은 강화의 싸주아리 쑥이었다. 2. 쑥의 채취시기별 함량을 분석한 결과 eupatilin과 jaceosidin 함량은 모두 5월 23일에서 6월 10일 사이 채취한 쑥에서 가장 높았다. 3 쑥의 식물체 부위별 함량을 분석한 결과, eupatilin 함량은 상위엽이 하위엽보다 2배가량 많이 함유되어 있었으나 jaceosidin 함량은 그 차이가 크지 않았다.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.385-394
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• 2020

Eupatilin is known to possess anti-apoptotic, anti-oxidative, and anti-inflammatory properties. We report here that eupatilin has a protective effect on the ethanol-induced injury in rats. Sprague-Dawley rats were divided into 6 groups: control, vehicle, silymarin, eupatilin 10 mg/kg, eupatilin 30 mg/kg, and eupatilin 100 mg/kg. Plasma levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were analyzed to determine the extent of liver damage. Total cholesterol (TC) and triglycerides (TG) were analyzed to determine the level of liver steatosis. Malondialdehyde level, superoxide dismutase (SOD) activity, and glutathione (GSH) level were analyzed to determine the extent of oxidative stress. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β were quantified to verify the degree of inflammation. Based on our findings, chronic alcohol treatment significantly changed the serum indexes and liver indicators of the model rats, which were significantly improved by eupatilin treatment. Rats in the eupatilin-treatment group showed reduced levels of AST, ALT, TG, TC, TNF-α, and IL-1β, increased SOD activity and GSH levels, and improved overall physiology compared to the alcoholic liver disease model rats. H&E staining also verified the eupatilin-mediated improvement in liver injury. In conclusion, eupatilin inhibits alcohol-induced liver injury via its antioxidant and anti-inflammatory effects.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.215.3-216
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• 2003

Eupatilin is a major active component of Stillen\ulcorner(Artemisia Herba Extract) having a potent antigastritic effect. We investigated the physical properties of eupatilin using high performance liquid chromatography. Solubility, stability & partition coefficient of eupatilin were investigated. pH-stability of eupatilin was examined over the broad range through pH1-9 at 37$^{\circ}C$ & it has good stability above the broad range pH. The solubility of eupatilin was extremely low but the value of logP was more than 2. Also, a high performance liquid chromatographic method was developed for the determination of eupatilin in rat plasma. (omitted)

• 한국작물학회지
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• 제49권6호
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• pp.452-456
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• 2004

약쑥의 eupatilin과 jaceosidin을 분리하여 그 화학구조를 분광학적 방법(^1H\;and\;^{13}C-NMR,\;MS)$으로 확인하였다. 이를 지표물질로 하여 HPLC분석조건과 HPLC용 검체의 조제, 표준 검량선을 작성하였다. 약쑥 eupatilin 성분의 검량선은 y=76069x+107329(r=0.9999), jaceosidin은 y=76651x+77399(r=0.9996)으로 각각 직선성이 인정되었다. 강화사자발쑥의 잎에는 eupatilin이 240mg(100g 잎), jaceosidin이 10mg(100g 잎) 함유되어 있고, 싸주아리쑥의 잎에는 eupatilin이 330mg(100g 잎), jaceosidin이 123mg(100g 잎)씩 각각 함유되어 있음이 확인되었다.

• Clinical and Experimental Reproductive Medicine
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• 제47권2호
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• pp.108-113
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• 2020

Objective: Endometrial fibrosis, the primary pathological feature of intrauterine adhesion, may lead to disruption of endometrial tissue structure, menstrual abnormalities, infertility, and recurrent pregnancy loss. At present, no ideal therapeutic strategy exists for this fibrotic disease. Eupatilin, a major pharmacologically active flavone from Artemisia, has been previously reported to act as a potent inducer of dedifferentiation of fibrotic tissue in the liver and lung. However, the effects of eupatilin on endometrial fibrosis have not yet been investigated. In this study, we present the first report on the impact of eupatilin treatment on transforming growth factor beta (TGF-β)-induced endometrial fibrosis. Methods: The efficacy of eupatilin on TGF-β-induced endometrial fibrosis was assessed by examining changes in morphology and the expression levels of fibrosis markers using immunofluorescence staining and quantitative real-time reverse-transcription polymerase chain reaction. Results: Eupatilin treatment significantly reduced the fibrotic activity of TGF-β-induced endometrial fibrosis in Ishikawa cells, which displayed more circular shapes and formed more colonies. Additionally, the effects of eupatilin on fibrotic markers including alpha-smooth muscle actin, hypoxia-inducible factor 1 alpha, collagen type I alpha 1 chain, and matrix metalloproteinase-2, were evaluated in TGF-β-induced endometrial fibrosis. The expression of these markers was highly upregulated by TGF-β pretreatment and recovered to the levels of control cells in response to eupatilin treatment. Conclusion: Our findings suggest that suppression of TGF-β-induced signaling by eupatilin might be an effective therapeutic strategy for the treatment of endometrial fibrosis.

• The Korean Journal of Physiology and Pharmacology
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• 제17권1호
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• pp.31-36
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• 2013

The present study was undertaken to investigate the influence of eupatilin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Eupatilin more significantly relaxed fluoride-induced vascular contraction than thromboxane $A_2$ or phorbol ester-induced contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, eupatilin significantly inhibited fluoride-induced increases in pMYPT1 levels. On the other hand, it didn't significantly inhibit phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the primarily inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1. This study provides evidence regarding the mechanism underlying the relaxation effect of eupatilin on agonist-induced vascular contraction regardless of endothelial function.

• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.383-390
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• 2014

Gastrointestinal motility consists of phasic slow-wave contractions and the migrating motor complex (MMC). Eupatilin (Stillen$^{(R)}$) has been widely used to treat gastritis and peptic ulcers, and various cytokines and neuropeptides are thought to be involved, which can affect gastrointestinal motility. We performed a study to identify the effects of eupatilin on lower gastrointestinal motility with electromechanical recordings of smooth muscles in the human ileum and colon. Ileum and colon samples were obtained from patients undergoing bowel resection. The tissues were immediately stored in oxygenated Krebs-Ringer's bicarbonate solution, and conventional microelectrode recordings from muscle cells and tension recordings from muscle strips and ileal or colonic segments were performed. Eupatilin was perfused into the tissue chamber, and changes in membrane potentials and contractions were measured. Hyperpolarization of resting membrane potential (RMP) was observed after administration of eupatilin. The amplitude, AUC, and frequency of tension recordings from circular and longitudinal smooth muscle strips and bowel segments of the ileum and colon were significantly decreased after admission of eupatilin. Eupatilin elicited dose-dependent decreases during segmental tension recordings. In conclusion, eupatilin (Stillen$^{(R)}$) showed inhibitory effects on the human ileum and colon. We propose that this drug may be useful for treating diseases that increase bowel motility, but further studies are necessary.