EUPATILIN

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H16O7
Molecular Weight	344.3154
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(C=C1OC)C2=CC(=O)C3=C(O2)C=C(O)C(OC)=C3O

InChI

InChIKey=DRRWBCNQOKKKOL-UHFFFAOYSA-N

InChI=1S/C18H16O7/c1-22-12-5-4-9(6-14(12)23-2)13-7-10(19)16-15(25-13)8-11(20)18(24-3)17(16)21/h4-8,20-21H,1-3H3

HIDE SMILES / InChI

Molecular Formula	C18H16O7
Molecular Weight	344.3154
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25352757
Curator's Comment: The description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/29353040 | https://www.ncbi.nlm.nih.gov/pubmed/19663482 | https://www.ncbi.nlm.nih.gov/pubmed/27698876 | https://www.drugs.com/international/stillen.html

Eupatilin (5,7-dihydroxy-3',4',6-trimethoxyflavone) is the major lipophilic flavonoid from Artemísia umbellifórmis, mountain wormwood used for the production of the celebrated alpine liqueur genepy. Eupatilin is the active ingredient of Stillen, a herbal drug from the Asian wormwood Artemisia asiatica, developed in South Korea for the treatment of gastritis and peptic ulcer. Eupatilin has been shown to exert cytoprotective and antiapoptotic effects on gastric and esophageal epithelial primary cells and is endowed with antispasmodic and antimutagenic properties, while apoptotic and anti-proliferative activities have been demonstrated on cancer cells. Eupatilin has also been evaluated, with promising results, in several assays of relevance for inflammation and allergy. Thus, this flavonoid inhibits in vitro mast cell degranulation and histamine release, shows in vivo anti-allergic properties is an antioxidant, inhibits 5-lipoxygenase and the leukotrienes synthesis, decreases prostaglandin E2 production, and inhibits the activation of nuclear transcription factor NF-κB and the expression of cyclooxygenase-2 and different pro-inflammatory cytokines, such as interleukins (IL-4, IL-6, and IL-8) and tumor necrosis factor-R (TNF-R)

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26225954	Agonist 2752		1.18 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Atopic dermatitis 64 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29353040	Primary	Basic research	Unknown Approved Use Unknown
Acute gastritis 1 Sources: https://clinicaltrials.gov/ct2/show/NCT01817556	Primary	Approved 8583	Stillen Approved Use Unknown
Chronic gastritis 4 Sources: https://clinicaltrials.gov/ct2/show/NCT01817556	Primary	Approved 8583	Stillen Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
48.58 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29980012/	100 mg/kg single, intragastric dose: 100 mg/kg route of administration: Intragastric experiment type: SINGLE co-administered:		EUPATILIN plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
4.52 μg × h/mL EXPERIMENT http://www.koreascience.or.kr/article/JAKO200311922086167.page	30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		EUPATILIN plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
193.514 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29980012/	100 mg/kg single, intragastric dose: 100 mg/kg route of administration: Intragastric experiment type: SINGLE co-administered:		EUPATILIN plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.101 h EXPERIMENT http://www.koreascience.or.kr/article/JAKO200311922086167.page	30 mg/kg single, intravenous dose: 30 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		EUPATILIN plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.825 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29980012/	100 mg/kg single, intragastric dose: 100 mg/kg route of administration: Intragastric experiment type: SINGLE co-administered:		EUPATILIN plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	inhibitor 2438 substrate 1193	substrate 1388 inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 227 CYP2C19 2057 CYP1A2 2153 CYP2C8 1057 CYP2A6 879	CYP2C19 1119 CYP2E1 729 UGT2B4 278 UGT1A1 479 UGT1A4 399 UGT1A7 249 CYP1A2 1197 CYP2C8 810 CYP2A6 626 CYP2B6 776 UGT1A10 331 UGT1A9 423 UGT1A8 323 UGT2B7 456 UGT1A6 343 UGT2B15 236 UGT2B17 237 UGT1A3 470

Drug as perpetrator

Target	Modality	Activity
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20877236/	moderate [IC50 104.9 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20877236/	moderate [IC50 48.1 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20877236/	moderate [IC50 58.7 uM]
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20877236/	no
CYP3A 317	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20877236/	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20877236/	yes [IC50 4.1 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/20877236/	yes [IC50 9.4 uM]

Drug as victim

Target	Modality	Activity
UGT2B15 236	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	likely
UGT2B17 237	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	likely
UGT2B7 456	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	likely
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	major [Km 14.4 uM]
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	minor [Km 4.5 uM]
UGT1A4 399	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	no
UGT1A6 343	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	no
UGT2B4 278	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 156 uM]
UGT1A1 479	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 16.9 uM]
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 161 uM]
UGT1A10 331	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 240.7 uM]
UGT1A8 323	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 40.1 uM]
UGT1A3 470	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 6.2 uM]
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 73.9 uM]
UGT1A9 423	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 8.4 uM]
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 88.6 uM]
UGT1A7 249	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes [Km 9.2 uM]
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/17701830/	yes

PubMed

Title	Date	PubMed
Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages.	2011-06-20	21565208
TNF-α induces expression of urokinase-type plasminogen activator and β-catenin activation through generation of ROS in human breast epithelial cells.	2010-12-15	20804741
Bioactivity-guided isolation of antiproliferative compounds from Centaurea arenaria.	2010-11	21031625
Effects of eupatilin and jaceosidin on cytochrome p450 enzyme activities in human liver microsomes.	2010-09-16	20877236
Impact of dietary polyphenols on carbohydrate metabolism.	2010-03-31	20480025
The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies.	2010	20339581
[Studies on flavones from Flos Chrysanthemi Indici].	2009-10	20112712
Inhibitory effect of eupatilin and jaceosidin isolated from Artemisia princeps on carrageenan-induced inflammation in mice.	2009-09-25	19505561
Topical anti-inflammatory activity of Eupatilin, a lipophilic flavonoid from mountain wormwood ( Artemisia umbelliformis Lam.).	2009-09-09	19663482
Eupatilin inhibits T-cell activation by modulation of intracellular calcium flux and NF-kappaB and NF-AT activity.	2009-09-01	19565564
Phosphorylation of Nrf2 at multiple sites by MAP kinases has a limited contribution in modulating the Nrf2-dependent antioxidant response.	2009-08-11	19668370
Eupatilin with heme oxygenase-1-inducing ability protects cultured feline esophageal epithelial cells from cell damage caused by indomethacin.	2009-04	19336889
Eupatilin exhibits a novel anti-tumor activity through the induction of cell cycle arrest and differentiation of gastric carcinoma AGS cells.	2009-04	19281788
The effects of DA-6034 on NF-kappaB activity induced by lipopolysaccharide or tumor necrosis factor alpha in a human colonic epithelial cell line.	2009-03-06	19260477
5,7-dihydroxy-3,4,6-trimethoxyflavone inhibits the inflammatory effects induced by Bacteroides fragilis enterotoxin via dissociating the complex of heat shock protein 90 and I kappaB alpha and I kappaB kinase-gamma in intestinal epithelial cell culture.	2009-03	19220840
Effects of DA-6034, a flavonoid derivative, on mucin-like glycoprotein and ocular surface integrity in a rabbit model.	2009	19998577
Eupatilin, isolated from Artemisia princeps Pampanini, enhances hepatic glucose metabolism and pancreatic beta-cell function in type 2 diabetic mice.	2008-10	18703253
Eupatilin inhibits H(2)O(2)-induced apoptotic cell death through inhibition of mitogen-activated protein kinases and nuclear factor-kappaB.	2008-08	18603343
The protective effect of eupatilin on indomethacin-induced cell damage in cultured feline ileal smooth muscle cells: involvement of HO-1 and ERK.	2008-06-19	18440740
Eupatilin protects gastric epithelial cells from oxidative damage and down-regulates genes responsible for the cellular oxidative stress.	2008-06	18299966
DA-6034, a derivative of flavonoid, prevents and ameliorates dextran sulfate sodium-induced colitis and inhibits colon carcinogenesis.	2008-02	18222973
Inhibitory effect of eupatilin and jaceosidin isolated from Artemisia princeps in IgE-induced hypersensitivity.	2007-12-15	17996677
In vitro metabolism of eupatilin by multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes.	2007-08	17701830
Analysis of eupatilin-human serum albumin interactions by means of spectroscopic and computational modelling.	2007-05	17524228
Jaceosidin induces apoptosis in ras-transformed human breast epithelial cells through generation of reactive oxygen species.	2007-01	17404061
Eupatilin has an antiapoptotic action on hepatocytes, in contrast to apoptotic actions on other cells.	2006-08	16988777
Eupatilin attenuates bile acid-induced hepatocyte apoptosis.	2006-08	16988766
[Studies on the flavonoids from whole herbs of Seriphidium terrae-albae].	2006-05	17048665
Eupatilin blocks mediator release via tyrosine kinase inhibition in activated guinea pig lung mast cells.	2005-12-10	16326424
Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human gastric cancer (AGS) cells.	2005	16393120
Eupatilin inhibits proliferation of ras-transformed human breast epithelial (MCF-10A-ras) cells.	2005	16393119
Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces cell cycle arrest in ras-transformed human mammary epithelial cells.	2004-09-15	15313404
Metabolism of eupatilin in rats using liquid chromatography/electrospray mass spectrometry.	2004-04	15103703
Antiproliferative constituents in plants 10. Flavones from the leaves of Lantana montevidensis Briq. and consideration of structure-activity relationship.	2002-07	12132661
Eupatilin, a pharmacologically active flavone derived from Artemisia plants, induces apoptosis in human promyelocytic leukemia cells.	2001-09-20	11551495
Mono- and sesquiterpenes and antifungal constituents from Artemisia species.	1999-02	10083848

Patents

Sample Use Guides

In Vivo Use Guide

DA-9601 (comprises 60 mg of Artemisia asiatica 95% ethanol extract) three times per day for 2 weeks

Route of Administration: Oral

In Vitro Use Guide

The 786 O human RCC cell line was used for activity evaluation. Cells were seeded into 96 well plates at 5x10^3 cells per well and cultured for 24 h at 37˚C to adhere. Following treatment with various concentrations of eupatilin (10, 20 and 40 μM) for 72 h, 10 μl of CCK 8 reagent was added to the cells, followed by incubation for 2 h at 37˚C. Subsequently, the optical density (OD) value was read at 450 nm using a Bio Rad ELISA microplate reader. Eupatilin significantly induced cell apoptosis and enhanced the production of reactive oxygen species (ROS) in 786 O cells.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:55:32 GMT 2025` Edited by `admin` on `Mon Mar 31 20:55:32 GMT 2025`
Record UNII	4D58O05490
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NSC-122413

Preferred Name

English

EUPATILIN

Common Name

English

2-(3,4-DIMETHOXYPHENYL)-5,7-DIHYDROXY-6-METHOXYCHROMEN-4-ONE

Systematic Name

English

Eupatilin [WHO-DD]

Common Name

English

Code System Code Type Description

NSC

122413