Eupatilin protects surrogate markers of NSAIDs induced enteropathy in patients taking both NSAIDs and proton pump inhibitor: Prospective randomized double-blind controlled trial

开始日期2021-06-01

申办/合作机构

Kyung Hee University Hospital at Gangdong

NCT04885751

/ Unknown status临床4期IIT

Compare the Effect of Eupatilin and Rebamipide on the Prevention of Gastroenteropathy in Patients With NSAIDs and Low Dose Steroid: A Single-center, Randomized, Open Labeled, Pilot Study

The purpose of this study is to evaluate the efficacy of eupatilin on the prevention of gastroenteropathy in patients with NSAIDs and low dose steroid by comparing with rebamipide.

开始日期2021-06-01

申办/合作机构

SMG-SNU Boramae Medical Center

[+1]

IRCT20180422039378N1

/ Completed临床3期IIT

Evaluation of the efficacy and safety of stillen in comparison with pentoprazole in controlling the symptoms of gastro-myopic reflux in patients referred to the gastroenterology clinic of Baqiyatallah Hospital

开始日期2017-04-19

申办/合作机构-

100 项与 Eupatilin 相关的临床结果

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100 项与 Eupatilin 相关的转化医学

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100 项与 Eupatilin 相关的专利（医药）

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631

项与 Eupatilin 相关的文献（医药）

2025-04-01·Food Chemistry

Characterization of free and bound polymethoxyflavones in the dried peel of Citrus reticulata “Chachi” through fingerprint RDA ions and reversed-phase column retention by UPLC-Q-TOF-MS/MS

Article

作者: Jin, Mingyu ; Li, Longqing ; Yu, Yahui ; Yan, Jing-Kun ; Yu, Xiangying ; Li, Difan

Polymethoxyflavones (PMFs) from citrus peel, including permethoxylated PMFs and hydroxylated PMFs (OH-PMFs), have attracted much attention due to their potential strong biological activities. However, characterization of PMFs through LC-MS analysis was challenged due to numerous substituent positions in flavone. In this study, twelve PMF standards were analyzed by UPLC-QTOF-MS/MS to present fingerprint retro-Diels-Alder (RDA) ions ([^0,2B]⁺, ^1,3 A and ^1,3B(C) associated ions). Based on UPLC-QTOF-MS/MS characteristics of PMFs, 29 PMFs, screened through extracted ion chromatograms in UPLC-QTOF-MS analysis, were identified in free and bound extracts from dried peel of Citrus reticulata "Chachi" through fingerprint RDA ions and reversed-phase column retention in UPLC-QTOF-MS/MS experiment. It was found that permethoxylated PMFs and 5-OH PMFs existed mainly in free form; while di/trihydroxy PMFs existed mainly in bound form in dried peel of Citrus reticulata "Chachi". The present study is expected to provide new analytical strategy in characterizing PMFs in PMFs metabolites and citrus.

2025-02-26·Chemical and Pharmaceutical Bulletin

Design, Synthesis, and Antitumor Activity of Novel Eupatilin Derivatives Based on the Mannich Reaction

Article

作者: Yang, Yanli ; Meng, Yaqi ; Cai, Zhiyan ; Wang, Yuqing ; Li, Shujiao ; Zhuang, Guo

Eupatilin, a natural bioactive flavone, is the active ingredient in traditional Chinese medicine Artemisia argyi Levl. et Vant. To enhance the antitumor effect of eupatilin, we designed a series of novel eupatilin-Mannich derivatives and investigated antitumor activity against several human cancer cell lines, including gastric cancer cells (AGS), esophageal cancer cells (Eca-109), and breast cancer cells (MDA-MB-231). Among all derivatives, the majority demonstrated superior antitumor activity compared to eupatilin, with compound 3d exhibiting the most effective antitumor activity against AGS cells. Furthermore, compound 3d effectively inhibited colony formation and migration of AGS cells. Network pharmacology combined with molecular docking studies indicated that compound 3d exerts antitumor activity by targeting the Hsp90AA1 and multiple signaling pathways. In addition, the Western blot experiment results showed that compound 3d reduced the expression of Hsp90AA1 in AGS cells, indicating that Hsp90AA1 may be the potential target of compound 3d. In summary, several novel eupatilin derivatives were prepared via the Mannich reaction, representing the first structure modification study of eupatilin. The mechanism of action of compound 3d was estimated through cell experiments, network pharmacology, molecular docking, and Western blot experiments, to provide lead compounds for the discovery of natural product-based antitumor candidates.

2025-02-01·Journal of Ethnopharmacology

Hepatoprotective efficacy of Argemone mexicana L. root in paracetamol-induced hepatotoxicity in a rat model

Article

作者: Raha, Anusree ; Rath, Goutam ; Kar, Biswakanth ; Rai, Vineet Kumar ; Bagchi, Anindya ; Ghosh, Goutam ; Rajwar, Tushar Kanti ; Dash, Priyanka ; Halder, Jitu ; Pradhan, Deepak ; Das, Chandan ; Das, Debajyoti ; Manoharadas, Salim

ETHNOPHARMACOLOGICAL RELEVANCEArgemone mexicana L. (Papaveraceae), a weed that thrives in the tropical and subtropical areas of South and Central America, Mexico, Caribbean Islands and India. In India, it has been used traditionally to treat vesicular calculus, inflammatory conditions, and hepatobiliary disorders.AIM OF THE STUDYThe present study was aimed to investigate the hepatoprotective efficacy of A. Mexicana roots in paracetamol (PCM)-induced toxicity rat.MATERIALS AND METHODSThe methanol extract of A. mexicana (MEAM) root was analyzed using Gas Chromatography-Mass Spectrometry (GC-MS) analysis to identify its compounds. Molecular docking analysis of the compounds was conducted against TGF-β and PPAR-α. The hepatoprotective activity of MEAM (200, 400 mg/kg) was evaluated in PCM (3000 mg/kg) intoxicated rats by measuring serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), total bilirubin (TB), total protein (TP), albumin (ALB), globulin (GLB), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Silymarin (100 mg/kg) was used as reference drug. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and lipid peroxidation (LPO) were investigated using liver homogenate. Additionally, the levels of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and anti-inflammatory cytokines interleukin-4 (IL-4) and interleukin-10 (IL-10) were studied. The results of the study were supported by histopathological examination.RESULTSGC-MS analysis revealed 163 compounds, from which eleven compounds were selected based on their docking scores against TGF-β and PPAR-α. MEAM (400 mg/kg) demonstrated a remarkable reduction in ALT, AST, ALP, GGT, and LDH in contrast to the PCM intoxicated group. A remarkable decline in TB and GLB, along with an increase in TP and ALB, was observed in the MEAM (400 mg/kg) group compared to the untreated PCM group. Rats receiving MEAM (400 mg/kg) exhibited a noticeable decrease in TC, TG, and LDL-C, along with an increase in HDL-C levels compared to PCM-induced untreated rats. The higher dose of MEAM also resulted in a significant decrease in TNF-α, IL-1β, and IL-6, and an increase in IL-4 and IL-10. Similarly, a notable elevation in SOD, CAT, and GSH, along with a decrease in MDA content, was observed in the group receiving MEAM (400 mg/kg). The histopathological result showed reduction of sinusoidal space and vesicular nuclei, with improvement of hepatocytes at the dose of MEAM (400 mg/kg). In molecular docking study, Eupatilin exhibited the highest docking scores of -10.4 kcal/mol and -9.1 kcal/mol against TGF-β and PPAR-α, respectively.CONCLUSIONSMEAM root at dose of 400 mg/kg exhibited hepatoprotective effect against PCM-induced toxicity rat. Eupatilin might be considered as a potential candidate for the hepatoprotective effect of A. mexicana root.

项与 Eupatilin 相关的新闻（医药）

2022-10-10

·药智网

10年做出全球首创！跨国巨头都失败的路，多格列艾汀为何成功？

近日，国家药品监督管理局批准华领医药技术（上海）有限公司申报的1类创新药多格列艾汀片（商品名：华堂宁）上市。该药品适用于改善成人2型糖尿病患者的血糖控制。图1 获批公告（图片来源：NMPA官网）值得骄傲的是，多格列艾汀是我国自主创新研发的降糖药物，也是全球第一款批准上市的GK激动剂。全球首创、中国首发！多格列艾汀赢在哪儿？多格列艾汀为何成功多格列艾汀是葡萄糖激酶（GK）激活剂，作用于胰岛、肠道内分泌细胞以及肝脏等葡萄糖储存与输出器官中的葡萄糖激酶靶点，改善2型糖尿病患者血糖稳态失调。图2 多格列艾汀结构式（图片来源：PubChem）临床研究显示2型糖尿病患者应用多格列艾汀治疗24周，餐后2小时的降幅较基线下降了2.81mmol/L，糖化血红蛋白从基线的最小平方平均变化（95%置信区间）为-1.07%[-1.19%，-0.95%]，糖化血红蛋白达标率达到了42.5%，在24周时达到了降低HbA1c水平的主要疗效终点。安全性评价中，多格列艾汀作为二甲双胍的附加疗法，在整个52周的治疗期间具有良好的耐受性和安全性，没有发生过多的药物相关的SAE或严重低血糖。图3 多格列艾汀3期临床试验(图片来源：参考文献[6])据悉，GK最早于1960s被发现，到2001年葡萄糖激酶激活剂（GKA）的药理学基础被报道后，有关GKA的研究蓬勃发展，迄今为止已经公布了100多项GKA专利，20多种GKA药物已经进入临床研究阶段，而华领医药的dorzagliatin（多格列艾汀）无疑是进展最快的一个（图4）。图4 葡萄糖激酶药理学及药物开发相关的重要事件（图片来源：华领官网）还有哪些GK激动剂？葡萄糖激酶（GK）是糖酵解中的关键酶之一，它的作用是维持葡萄糖的稳态。自2003年以来，大量关于GK激活剂的合成和传统抗糖尿病植物的研究被报道，GK激活剂与离活性位点20Å的变构位点相互作用，激活GK。该变构位点有一个宽阔的空腔，因此，可以容纳不同的化学结构(图5)。图5 GK变构结合位点（图片来源：PDB:1V4S，图片由pyMol绘制）由于GK激活剂有潜在的不良反应，如低血糖、高甘油三酯血症、脂肪肝或肝脂肪变性，因此，研究人员一直致力于获得无不良反应的GK激活剂来治疗糖尿病。2003年，罗氏公司的科学家们首先描述了小分子GK激动剂。随后，许多其他小组也披露了葡萄糖激酶。Grimsby等人通过筛选12万个结构不同的合成化合物发现葡萄糖激酶的激活剂。通过对最初苗头化合物进行优化，确定了RO-28-0450（图6），R构型的RO-28-1675具有双重作用机制。它增强了胰腺的胰岛素释放，并刺激了肝脏的葡萄糖利用。图6 RO-28-0450的结构式（图片来源：参考文献3）Array BioPharma公司的报道了GK激动剂ARRY-403，随后被授权给Amgen公司，成为AMG-151。它是一种口服的异生葡萄糖激酶（GK）激活剂，体外有效地激活人类葡萄糖激酶（GK）（EC50=79 nM），具有良好的体外类药物特性（水溶性、细胞渗透性、低低的药物相互作用潜力、低的预测肝脏清除率），以及对广泛的受体和酶的选择性。图7 AMG-151的化学结构（图片来源：PubChem）其他一些制药公司，针对GK也有所布局，这些小分子GK激动剂的可以按化学结构分类（尿素基团、取代的芳基中心酰胺和其他类型）。例如，化合物1-5（图7）是已进入II期临床试验的一些GKA，这些化合物从结构上看，都具有一些共同的结构特征（图8，蓝色）图8 代表性GK激动剂（图片来源：J.Med.Chem.2014,57,8180−8186）除了合成的小分子化合物，一些植物（如Allium hirtifolium和Sapiumellipticum）的提取物或活性成分（如ganoderan B、glucolipsins A和B、eupatilin、coagulanolide、mangiferin和kaempferol）也具有强大的GK激动活性。GK激动剂面临挑战GK激活剂面临的最大问题，是关于疗效和安全性的方面的问题。研究证明，低血糖症、脂肪肝的开始、肝细胞脂质化，以及随着时间的推移疗效下降是使用GK激活剂观察到的最重要的副作用。例如，Piragliatin和MK-0941被证明会频繁地引起低血糖发作。此外，根据与激活GK有关的病理生理过程，GK激动剂可能会导致血脂异常，使肝脏新生脂肪生成的增加，例如，化合物MK-0941被证明可引起急性高脂血症。为了应对这些副作用，研究人员设计了（1）对葡萄糖水平有较高依赖性的部分激活剂，以减少低葡萄糖浓度下过度激活的风险。例如，使用部分GK激活剂PF-04937319，可以降低了发生低血糖的几率。（2）开发肝脏选择性的剂型，来降低副作用。例如TTP399，正在被开发为T1D患者的胰岛素辅助治疗。2021年4月，FDA授予TTP399治疗T1D的突破性疗法称号。小结糖尿病是一种影响全世界人民的代谢性疾病，其发病率在发达国家和发展中国家都在逐日增加。激活GK的小分子药物为恢复/改善T2D患者的血糖调节提供了一种替代策略。GK激活剂通过增加胰岛素分泌和糖原合成来减少肝脏葡萄糖的产生。随着双作用的新型GK激活剂多格列艾汀的上市以及和肝脏选择性的新型GK激活剂TTP399的报道后，可以预见，疗效更可靠、副作用更低的新一代的GK激动剂的研究会迎来新的热潮。参考文献[1]https://www.nmpa.gov.cn/yaowen/ypjgyw/20221008173753169.html[2]https://www.huamedicine.com/dorzagliatin[3]Grimsby J,Sarabu R,Corbett W L,et al.Allosteric activators of glucokinase:potential role in diabetes therapy[J].Science,2003,301(5631):370-373.[4]Sharma P,Singh S,Sharma N,et al.Targeting human Glucokinase for the treatment of type 2 diabetes:an overview of allosteric Glucokinase activators[J].Journal of Diabetes&Metabolic Disorders,2022:1-9.[5]Gaitonde P,Garhyan P,Link C,et al.A Comprehensive Review of Novel Drug–Disease Models in Diabetes Drug Development[J].Clinical pharmacokinetics,2016,55(7):769-788.[6]Zhu D,Li X,Ma J,et al.Dorzagliatin in drug-naïve patients with type 2 diabetes:a randomized,double-blind,placebo-controlled phase 3 trial[J].Nature Medicine,2022,28(5):965-973.声明：如需转载，请务必注明文章作者和来源。如涉及作品内容、版权和其它问题，请您留言，我们将在第一时间删除。责任编辑 | 八角商务合作 | 张老师 13368443108转载开白 | 马老师 18323856316（同微信）药智网原创作品 | 尽情分享朋友圈 | 转载请联系授权— Tips —如果您有医药行业相关的线索或对医药政策、研发创新、资本市场、产业发展有深度观察欢迎投稿给我们马老师 18323856316（同微信）邮箱：maxuelian@yaozh.com发现“分享”和“赞”了吗，戳我看看吧

小分子药物创新药

100 项与 Eupatilin 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	A02B	-

研发状态

批准上市

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适应症	国家/地区	公司	日期
胃炎	韩国	Dong-A Pharmaceutical Co., Ltd.	2005-04-29
胃溃疡	韩国	Dong-A Pharmaceutical Co., Ltd.	2005-04-29

未上市

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适应症	最高研发状态	国家/地区	公司	日期
过敏	药物发现	韩国	Sungkyunkwan University	2005-03-20
过敏	药物发现	韩国	Samsung Biomedical Research Institute	2005-03-20

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


UEGW2022	N/A	出血	-	Eupatilin	製願觸蓋簾襯廠憲醖範(觸網壓選構齋鹽襯簾製) = 網壓遞選範鬱觸淵憲網壓廠積醖鹽壓淵醖簾襯 (積選糧選艱夢鏇觸糧夢 )	-	2022-10-09
				Aspirin	製願觸蓋簾襯廠憲醖範(觸網壓選構齋鹽襯簾製) = 願糧齋憲鬱積齋齋衊範壓廠積醖鹽壓淵醖簾襯 (積選糧選艱夢鏇觸糧夢 )
UEGW2019	N/A	胃食管反流	-	Pantoprazole 40mg + DA-5204	(獵鬱願網餘鑰醖構製鹹) = 簾窪憲鑰鬱齋蓋鏇簾網構廠鹽觸積鏇願鑰鹹簾 (淵鏇鏇餘遞鑰壓構選夢 )	-	2019-10-01
				Pantoprazole 40mg + Placebo	(獵鬱願網餘鑰醖構製鹹) = 繭壓夢廠餘餘蓋鹽窪淵構廠鹽觸積鏇願鑰鹹簾 (淵鏇鏇餘遞鑰壓構選夢 )
NCT02282670 (Pubmed)	临床3期	胃炎	434	DA-5204	壓遞鹽選積網築憲窪夢(壓構繭鹽觸範醖憲蓋鹽) = AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group 鹹構選衊餘遞觸鹽顧繭 (簾窪夢襯繭齋廠選顧艱 )	积极	2017-11-01
				DA-9601