ICARIIN

First approved in 2013

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C33H40O15
Molecular Weight	676.6617
Optical Activity	UNSPECIFIED
Defined Stereocenters	10 / 10
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(C=C1)C2=C(O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](O)[C@H]3O)C(=O)C4=C(O2)C(CC=C(C)C)=C(O[C@@H]5O[C@H](CO)[C@@H](O)[C@H](O)[C@H]5O)C=C4O

InChI

InChIKey=TZJALUIVHRYQQB-XLRXWWTNSA-N

InChI=1S/C33H40O15/c1-13(2)5-10-17-19(45-33-28(42)26(40)23(37)20(12-34)46-33)11-18(35)21-24(38)31(48-32-27(41)25(39)22(36)14(3)44-32)29(47-30(17)21)15-6-8-16(43-4)9-7-15/h5-9,11,14,20,22-23,25-28,32-37,39-42H,10,12H2,1-4H3/t14-,20+,22-,23+,25+,26-,27+,28+,32-,33+/m0/s1

HIDE SMILES / InChI

Description
Sources: https://clinicaltrials.gov/ct2/show/NCT01979133 | https://www.ncbi.nlm.nih.gov/pubmed/26809351 | https://www.ncbi.nlm.nih.gov/pubmed/18778098 | https://www.ncbi.nlm.nih.gov/pubmed/17120748 | https://www.ncbi.nlm.nih.gov/pubmed/24550686

Icariin is a naturally occurring compound isolatable from several plant species within the genus Epimedium which is mostly endemic to China. Plant extracts containing icarrin have been used in traditional Chinese medicine as aphrodisiacs and to treat erectile dysfunction. Icariin has been investigated in humans as a treatment method for bipolar disorder and alcohol or cocaine abuse (Phase III). For the treatment of impotence, icariin has been shown to be a weak PDE5 inhibitor capable of enhancing the production of nitric oxide. Also related to PDE5 activity icarrin has been investigated as a potential treatment in mouse models of Alzheimer's disease. Icariin is sold worldwide as an over-the-counter medication for sexual performance, athletic performance, and other health benefits (it improves memory function, protects from osteoporosis, etc).

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
cGMP-specific 3',5'-cyclic phosphodiesterase 6 Target ID: O76074 Gene ID: 8654.0 Gene Symbol: PDE5A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/18778098	Inhibitor 8504		5.9 µM [IC50]
Beta-secretase 1 21 Target ID: P56818 Gene ID: 23821.0 Gene Symbol: Bace1 Target Organism: Mus musculus (Mouse) Sources: https://www.ncbi.nlm.nih.gov/pubmed/24550686	Interacts 323

Conditions

Condition	Modality	Highest Phase	Product
Bipolar disorder 34 Sources: https://clinicaltrials.gov/ct2/show/NCT01979133	Primary	Phase III 665	Unknown Approved Use Unknown
Substance use disorder 2 Sources: https://clinicaltrials.gov/ct2/show/NCT01979133	Primary	Phase III 665	Unknown Approved Use Unknown
Erectile dysfunction 35 Sources: https://www.icariinhealth.com/pages/horny-goat-weed-icariin	Primary	Approved 8583	Icariin 60 Approved Use Unknown
Alzheimer’s disease 278 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24513083	Primary	Basic research	Unknown Approved Use Unknown
Osteoporosis 101 Sources: https://worldabs.com/products/icariin-60-horny-goat-weed	Primary	Approved 8583	Icariin 60 Approved Use Unknown

PubMed

Title	Date	PubMed
Simple and sensitive liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of five Epimedium prenylflavonoids in rat sera.	2009-01-01	19083275
Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells.	2008-11-14	18789310
[Effect of icariin on intermediate and advanced activation of murine T lymphocytes in vitro].	2008-11	18992191
[Primary study on effect of various components of modified formula radix hedysari on peripheral nerve regeneration].	2008-09	18822727
Potent inhibition of human phosphodiesterase-5 by icariin derivatives.	2008-09	18778098
Intestinal absorption mechanisms of prenylated flavonoids present in the heat-processed Epimedium koreanum Nakai (Yin Yanghuo).	2008-09	18459036
Involvement of p38MAPK and reactive oxygen species in icariin-induced cardiomyocyte differentiation of murine embryonic stem cells in vitro.	2008-08	18484897
Antiosteoporotic chemical constituents from Er-Xian Decoction, a traditional Chinese herbal formula.	2008-07-23	18501540
Fast quality control of Herba Epimedii by using Fourier transform infrared spectroscopy.	2008-07	17913573
Chemical markers for the quality control of herbal medicines: an overview.	2008-06-28	18588699
Determination of icariin in rat plasma by reverse-phase high-performance liquid chromatography after oral administration of a lipid-based suspension of Epimedium koreanum extract.	2008-06	18254138
Involvement of NF-kappaB and AP-1 activation in icariin promoted cardiac differentiation of mouse embryonic stem cells.	2008-05-31	18423597
Icariin induces osteogenic differentiation in vitro in a BMP- and Runx2-dependent manner.	2008-05-02	18295595
[Absorption mechanism of icariin across Caco-2 monolayer model].	2008-05	18720868
Effects of icariin combined with Panax notoginseng saponins on ischemia reperfusion-induced cognitive impairments related with oxidative stress and CA1 of hippocampal neurons in rat.	2008-05	18398927
Reactive oxygen species involved in prenylflavonoids, icariin and icaritin, initiating cardiac differentiation of mouse embryonic stem cells.	2008-04-01	17985362
Simultaneous extraction of epimedin A, B, C and icariin from Herba Epimedii by ultrasonic technique.	2008-04	17951093
Simultaneous determination of seven flavonoids in Epimedium using pressurized liquid extraction and capillary electrochromatography.	2008-03	18293424
A rapid method for simultaneous determination of 15 flavonoids in Epimedium using pressurized liquid extraction and ultra-performance liquid chromatography.	2008-01-22	17961954
Statistically designed enzymatic hydrolysis for optimized production of icariside II as a novel melanogenesis inhibitor.	2008-01	18239426
Ethanol extract from Epimedium brevicornum attenuates left ventricular dysfunction and cardiac remodeling through down-regulating matrix metalloproteinase-2 and -9 activity and myocardial apoptosis in rats with congestive heart failure.	2008-01	18097624
Effects of total flavonoids and flavonol glycosides from Epimedium koreanum Nakai on the proliferation and differentiation of primary osteoblasts.	2008-01	17482445
Trace analysis of icariin in human serum with dansyl chloride derivatization after oral administration of Epimedium decoction by liquid chromatography tandem mass spectrometry.	2007-12-15	18023626
Effect of lipid-based suspension of Epimedium koreanum Nakai extract on sexual behavior in rats.	2007-12-03	17890032
Simultaneous determination of icariin, icariside II and osthole in rat plasma after oral administration of the extract of Gushudan (a Chinese compound formulation) by LC-MS/MS.	2007-12-01	18006391
Protective effect of icariin on DNA against radical-induced oxidative damage.	2007-12	18053336
Simultaneous determination of nine flavonoids and qualitative evaluation of Herba Epimedii by high performance liquid chromatography with ultraviolet detection.	2007-12	18008281
LC-MS/MS method for the simultaneous determination of icariin and its major metabolites in rat plasma.	2007-11-30	17706393
[Systematic studies on quality of main species of Herba epimedii].	2007-11	18309658
[Effects of Erxian Decoction and its separate prescriptions on the levels of luteinizing hormone and follicle-stimulating hormone in anterior pituitary cells from female rats].	2007-11	17997943
Icariin enhances the osteogenic differentiation of bone marrow stromal cells but has no effects on the differentiation of newborn calvarial osteoblasts of rats.	2007-10	18236786
Pharmacological activity of cardiovascular agents from herbal medicine.	2007-10	17979689
Icariin promotes expression of PGC-1alpha, PPARalpha, and NRF-1 during cardiomyocyte differentiation of murine embryonic stem cells in vitro.	2007-10	17883938
Simultaneous quantitation of five flavonoid glycosides in Herba Epimedii by high-performance liquid chromatography-tandem mass spectrometry.	2007-09-20	17879228
Simultaneous determination of 15 flavonoids in Epimedium using pressurized liquid extraction and high-performance liquid chromatography.	2007-09-07	17606269
[Research on quality of Epimedium extract in market].	2007-09	18051889
Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro.	2007-08-16	17764702
[HPLC-MS3 analysis of chemical constituents in Epimedium brevicornum].	2007-08	18027664
Hypouricemic action of selected flavonoids in mice: structure-activity relationships.	2007-08	17666819
Protective effects of icariin against learning and memory deficits induced by aluminium in rats.	2007-08	17600559
Icariin enhances endothelial nitric-oxide synthase expression on human endothelial cells in vitro.	2007-07	17499557
HPLC analysis and pharmacokinetics of icariin in rats.	2007-06	17623472
Chemical constituents of roots of Epimedium wushanense and evaluation of their biological activities.	2007-06	17613817
Icariin inhibits the osteoclast formation induced by RANKL and macrophage-colony stimulating factor in mouse bone marrow culture.	2007-05	17557750
Icariin from Epimedium brevicornum attenuates chronic mild stress-induced behavioral and neuroendocrinological alterations in male Wistar rats.	2007-05	17509675
[Comparison of antioxidative and antitumor activities of six flavonoids from Epimedium koreanum].	2007-04	17608228
Vasorelaxant effects of icariin on isolated canine coronary artery.	2007-04	17438405
[A review on research of raw material and cut crude drug of Herba epimedii in last ten years].	2007-03	17552145
Comparison between HPLC and HPTLC densitometry for the determination of icariin from Epimedium koreanum extracts.	2007-03	17461110
[Effect of er xian decoction and its subdivisions on granulosa cells secretory function in rats].	2006-06	17569367

Patents

Sample Use Guides

In Vivo Use Guide

In an open-label pilot trial, adults with current bipolar disorder and current cocaine or alcohol use disorders were treated with 100 mg/day icariin. After 3 weeks patients who had less than 30% reduction in the Hamilton Rating Scale for Depression or still abusing substances were titrated up to a dose of 200 mg/day. At week 6 patients who had less than 50% reduction in HAMD score continued to abuse alcohol/cocaine were titrated up to a maximum dose of 300 mg/day.

Route of Administration: Oral

In Vitro Use Guide

Isolated segments of rabbit corpus cavernosum were exposed to increasing concentrations of icariin while the accumulation of cGMP and cAMP was monitored by means of a 1251 radioimmunoassay. Icariin increased accumulated cGMP and cAMP in a dose-dependent manner. An EC50 of 4.62 uM was determined for icariin, which was contrasted to an EC50 of 0.42 uM for Sildenafil under similar conditions.

Name

Type

Language

ICARIIN

Common Name

English

EPIMEDII HERBA ICARIIN [MI]

Preferred Name

English

4H-1-BENZOPYRAN-4-ONE, 3-((6-DEOXY-.ALPHA.-L-MANNOPYRANOSYL)OXY)-7-(.BETA.-D-GLUCOPYRANOSYLOXY)-5-HYDROXY-2-(4-METHOXYPHENYL)-8-(3-METHYL-2-BUTEN-1-YL)-

Systematic Name

English

Classification Tree Code System Code

DSLD

1125 (Number of products:24)