CYNARINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H24O12
Molecular Weight	516.4509
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@@H]1C[C@](C[C@@H](OC(=O)\C=C\C2=CC=C(O)C(O)=C2)[C@H]1O)(OC(=O)\C=C\C3=CC=C(O)C(O)=C3)C(O)=O

InChI

InChIKey=YDDUMTOHNYZQPO-RVXRWRFUSA-N

InChI=1S/C25H24O12/c26-15-5-1-13(9-17(15)28)3-7-21(31)36-20-12-25(24(34)35,11-19(30)23(20)33)37-22(32)8-4-14-2-6-16(27)18(29)10-14/h1-10,19-20,23,26-30,33H,11-12H2,(H,34,35)/b7-3+,8-4+/t19-,20-,23+,25-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16332114 | http://ebiotec.com/en/hepatosar/ | http://www.organic-herb.com/Product/552.html

Cynarine (Cynarin) is the most noteworthy active ingredient of the artichoke, and is considered a medicinal foodstuff due to its beneficial effect on the organism, derived from its condition as a stimulant of bile secretion (choleretic effect). Cynarine is present in artichoke leaves and has a beneficial effect on the control of gallstones, helps control cholesterol levels and improves gallbladder function. Chlorogenic acid and cynarin have been shown to have activity against oxidative stress in human leukocytes, whereas cynarin has also been shown to have hypocholesterolemic, hepatoprotective, and, more recently, antihuman immunodeficiency virus-1 (anti-HIV-1; 44) activities. Cynarin had marked antioxidant, anticholinergic, reducing ability, radical-scavenging, and metal-binding activities.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Collagen degradation 1 Target ID: WP2708 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8824943	Inhibitor 8504
Acetylcholinesterase 209 Target ID: CHEMBL220 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25792498	Inhibitor 8504		243.67 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypertriglyceridemia 20 Sources: https://www.ncbi.nlm.nih.gov/pubmed/4427557 https://www.ncbi.nlm.nih.gov/pubmed/6897455 https://www.ncbi.nlm.nih.gov/pubmed/3775065 http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2011/12/WC500119940.pdf	Primary	Phase I 438	Unknown Approved Use Unknown
Nephrotic syndrome 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/4850037	Primary	Phase I 438	Unknown Approved Use Unknown
Indigestion 1 Sources: http://www.nutragreenbio.com/product/artichoke-extract https://www.mdidea.com/products/proper/proper06307.html	Palliative	Approved 8583	Cynara scolymus Approved Use Digestive complaints, Dyspepsia
Hyperlipidemia 82 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2011/12/WC500119940.pdf https://www.rxlist.com/consumer_artichoke_cynara_scolymuscynarin/drugs-condition.htm https://reference.medscape.com/drug/cynara-scolymus-cynarin-artichoke-344503	Palliative	Approved 8583	Cynara scolymus Approved Use Hyperlipidemia

C_max

Value	Dose	Co-administered	Analyte	Population
27.9 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/20058327/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		CYNARINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
12.8 ng/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/20058327/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		1,5-DIFERULOYLQUINIC ACID plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
151 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/20058327/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		CYNARINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN
94 ng × h/mL CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/20058327/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		1,5-DIFERULOYLQUINIC ACID plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.6 h CLINICAL TRIAL https://pubmed.ncbi.nlm.nih.gov/20058327/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		CYNARINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 1087 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 OATP1B1 1079 CYP19A1 429 CYP1A2 2153 OAT3 747 OATP2B1 157 OAT1 725 P-gp 1741	P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281769#section=Biological-Test-Results Page: 5.0	inconclusive [IC50 15.4871 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281769#section=Biological-Test-Results Page: 6.0	inconclusive [IC50 24.5454 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281769#section=Biological-Test-Results Page: 86.0	no
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281769#section=Biological-Test-Results Page: 64.0	no
OAT3 749	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24636064/	weak
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24636064/	weak
OATP2B1 162	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24636064/	weak
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281769#section=Biological-Test-Results Page: 4.0	yes [IC50 12.3018 uM]
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281769#section=Biological-Test-Results Page: 36.0	yes [IC50 27.5404 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281769#section=Biological-Test-Results Page: 6.0	yes [IC50 27.5404 uM]
OAT1 730	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24636064/	yes [IC50 6.03 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23034269/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281769#section=Biological-Test-Results Page: 63 \| 64	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/5281769#section=Biological-Test-Results Page: 20.0

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

Cynarin (100 and 200 mg/kg body weight) administered intravenously to rabbits, lowered serum cholesterol by about 20% Triton WR 1339-induced hypercholesterolaemia. In rats it was significantly lowered (p=0.05-0.02) by cynarin after intraperitoneal administration (2*200 mg/kg body weight).

Route of Administration: Other

In Vitro Use Guide

Cynarin and caffeic acid showed significant cytoprotective activity (p<0.01 at 1 mg/ml) against carbon tetrachloride in isolated rat hepatocytes, reducing leakage of the liver enzymes glutamine oxaloacetic transaminase and glutamic pyrovic transaminase.

Name

Type

Language

CYNARINE

Official Name

English

LISTROCOL

Preferred Name

English

PLEMOCIL

Brand Name

English

1-CARBOXY-4,5-DIHYDROXY-1,3-CYCLOHEXYLENEBIS-(3,4-DIHYDROXYCINNAMATE)

Common Name

English

cynarine [INN]

Common Name

English

CYNARINE [MI]

Common Name

English

(1R-(1.ALPHA.,3.ALPHA.,4.ALPHA.,5.BETA.))-1,3-BIS((3-(3,4-DIHYDROXYPHENYL)-1-OXO-2-PROPENYL)OXY)-4,5-DIHYDROXYCYCLOHEXANECARBOXYLIC ACID

Common Name

English

CYCLOHEXANECARBOXYLIC ACID, 1,3-BIS(((2E)-3-(3,4-DIHYDROXYPHENYL)-1-OXO-2-PROPEN-1-YL)OXY)-4,5-DIHYDROXY-, (1R,3R,4S,5R)-

Systematic Name

English

CYNARINE [MART.]

Common Name

English

3,4-DIHYDROXYCINNAMIC ACID 1-CARBOXY-4,5-DIHYDROXY-1,3-CYCLOHEXYLENE ESTER

Common Name

English

1,3-DICQA

Common Name

English

1,3-DICAFFEOYLQUINIC ACID (CONSTITUENT OF ECHINACEA ANGUSTIFOLIA ROOT, ECHINACEA PALLIDA ROOT, ECHINACEA PURPUREA ROOT AND ECHINACEA PURPUREA AERIAL PARTS) [DSC]

Common Name

English

3,4-DIHYDROXYCINNAMIC ACID, 1-CARBOXY-4,5-DIHYDROXY-1,3-CYCLOHEXYLENE ESTER

Common Name

English

1,3-DICAFFEOYLQUINIC ACID

Common Name

English

Cynarine [WHO-DD]

Common Name

English

(1R,3R,4S,5R)-1,3-BIS((3-(3,4-DIHYDROXYPHENYL)-1-OXO-2-PROPEN-1-YL)OXY)-4,5-DIHYDROXYCYCLOHEXANECARBOXYLIC ACID

Systematic Name

English

CAFFEIC ACID 1-CARBOXY-4,5-DIHYDROXY-1,3-CYCLOHEXYLENE ESTER

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C66913