Synonym name: Anhydroicaritin
Catalogue No.: BP0759
Cas No.: 118525-40-9
Formula: C₂₁H₂₀O₆
Mol Weight: 368.385
Botanical Source: Epimedium spp.

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

​Description:

Icaritin, a potent inhibitor of transcription factor SREBPs, which exhibits a variety of biological activities, such as activation of cancer cell apoptosis and inhibition of growth, hormone regulation, protection against beta amyloid-induced neurotoxicity, and promotion of neuronal and cardiac cellular differentiation. Icaritin shows potent anti-leukemia activity on chronic myeloid leukemia in vitro and in vivo by regulating MAPK/ERK/JNK and JAK2/STAT3 /AKT signalings.

References:

Oncotarget. 2015 Apr 30;6(12):10460-72.    

Icaritin suppresses multiple myeloma, by inhibiting IL-6/JAK2/STAT3.    

Icaritin is an active prenylflavonoid derived from Epimedium genus, a traditional Chinese medicine. Icaritin has a wide range of pharmacological and biological activities, including cardiovascular function improvement, hormone regulation and antitumor activity. 

METHODS AND RESULTS:

Here, we investigated the effect of Icaritin on multiple myeloma (MM) in vitro and in vivo. Icaritin inhibited cell growth of MM cell line and primary MM cells. In contrast, Icaritin had low or no cytotoxic effect on normal hematopoiesis. We also demonstrated that in MM xenograft mouse models, Icaritin suppressed tumor growth and decreased serum IL-6 and IgE levels, but did not show adverse reactions such as body weight loss. The anti-MM activity of Icaritin was mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling. 

CONCLUSIONS:

We suggest that Icaritin can be further tested in clinical trials in MM.    

Eur J Pharmacol. 2004 Nov 19;504(3):147-53.    

Proliferation-stimulating effects of icaritin and desmethylicaritin in MCF-7 cells.    

Icariin, Icaritin and desmethylIcaritin are constituents of Epimedium with a similar structure to genistein and daidzein. 

CONCLUSIONS:

Using the modified MCF-7 cell proliferation assay (E-SCREEN assessment system), these compounds were tested for their estrogen-like activities. Icaritin and desmethylIcaritin, but not icariin, strongly stimulated the proliferation of MCF-7/BUS cells. Cell cycle analysis revealed that the proliferation stimulatory effect was associated with a marked increase in the number of MCF-7/BUS cells in S phase and a significant increase in the G2/M population, with effects similar to those of estradiol. These actions were dose dependent (range from 1 nM to 10 microM) and could be significantly inhibited by the specific estrogen receptor antagonist ICI 182,780 [7 alpha-[9(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl)-estra-1,3,5(10)-triene-3,17beta-diol)]. The estrogen receptor-regulated progesterone receptor and PS2 mRNA levels were increased by treatment with Icaritin or desmethylIcaritin within 24 h and the effects were also reversed by ICI 182,780.

CONCLUSIONS:

It was concluded that Icaritin and desmethylIcaritin are novel phytoestrogens and that the estrogenic effects of Icaritin and desmethylIcaritin are mediated by the estrogen receptor.    

Phytomedicine. 2014 Oct 15;21(12):1633-7.    

Synergistic inhibitory effect of Icariside II with Icaritin from Herba Epimedii on pre-osteoclastic RAW264.7 cell growth.    

Increasing evidence shows the therapeutic superiority of herbal extracts in comparison to isolated single constituents. One of the reasons may be attributed to the synergy effect of compound combinations. Flavonoids from Herba Epimedii have been shown to have therapeutic effect against bone loss. Our previous study showed that Icariside II inhibited pre-osteoclast RAW264.7 growth. The aim of this study was to investigate whether the activity of Icariside II is synergized by other components of Herba Epimedii. 

METHODS AND RESULTS:

The inhibitory activity of Icariside II was significantly enhanced in the presence of the extract of Herba Epimedii (EHE) at the ratio of 1:1, 1:5 and 1:10. Icaritin, another flavonoid constituent, was shown here to inhibit RAW264.7 growth in a dose-dependent manner. Further, we found that Icariside II, together with Icaritin, synergistically inhibited RAW264.7 growth. The synergistic effect is significant when the ratio of Icariside II and Icaritin was 10:1, 5:1, 1:1, 1:2, and 1:5, respectively. 

CONCLUSIONS:

In conclusion, Icaritin were an active component. The inhibitory activity of Icariside II on pre-osteoclast RAW264.7 growth was synergized by Icaritin, which maybe contribute to the efficiency of Herba Epimedii extract on curing bone-related diseases, such as osteoporosis. 

HPLC of Icaritin

HNMR of Icaritin

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Icaritin, as the main isoprene flavonoid derivative in epimedium spp., has attracted significant attention in recent years due to its diverse bioactivity and potential medicinal value. Epimedium is not only widely used in traditional Chinese medicine to tonify the kidneys and enhance yang, strengthen muscles and bones, but has also shown significant pharmacological activity in anti-tumor, anti-osteoporosis, and immune regulation, making it a research hotspot in the fields of natural product pharmacology and drug development. This paper aims to systematically review the chemical structure and physicochemical properties of epimedium, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and to explore its clinical application prospects and future development directions, aiming to provide theoretical basis and reference for related research and drug development.

Chemical structure and physicochemical properties

Epimedium (CAS No.: 118525-40-9) is a typical isoprene flavonoid derivative with a molecular formula C21H20O6 and a molecular weight of 368.3850. Its structural core is a flavonoid backbone connected to isoprene side chains, giving it unique biological activity. The LogP value of epimedium is 3.8041, indicating moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. Its topological pole surface area (TPSA) is 100.1300, indicating certain polarity, which may affect its solubility and bioavailability. Low water solubility (0.0543 mg/mL) suggests limited solubility in the aqueous phase, and its bioavailability needs to be improved through appropriate formulation techniques. Low blood-brain barrier permeability indicates limited distribution in the central nervous system. The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity. The Ames test result was 0.6, indicating a low genotoxicity risk and a solid safety foundation.

Plant Origins and Extraction Methods

Epimedium mainly comes from plants of the genus Epimedium, especially species such as Epimedium brevicornum Maxim., Epimedium sagittatum, and Epimedium pubescens. As a traditional Chinese medicinal herb, Epimedium is widely distributed in China and East Asia, and has long been used to treat kidney deficiency, osteoporosis, and sexual dysfunction.

There are various methods for extracting epimedium, commonly using organic solvent extraction combined with column chromatography separation. Traditional extraction mostly uses ethanol or methanol as solvents, improving extraction efficiency through reflux or ultrasound-assisted extraction. After concentration and separation purification, the extract was analyzed and purified using high-performance liquid chromatography (HPLC) for component analysis and purity detection. In recent years, supercritical CO2 extraction and membrane separation technologies have also been introduced to improve extraction purity and yield, while reducing the use of organic solvents, in line with the concept of green chemistry.

Pharmacological activity research

The pharmacological activities of epimedium cover multiple aspects, including anti-tumor, anti-osteoporosis, immunomodulatory, and anti-inflammatory effects.

Antitumor activity

Epimedium exhibits significant inhibitory effects on various tumor cells. Notably, in the chronic myeloid leukemia (CML) model, epimedium inhibited the proliferation of K562 cells with an IC50 of 8 μM, and 13.4 μM and 18 μM for the chronic phase (CML-CP) and acute change phase (CML-BC) of primary CML cells, respectively, demonstrating strong anti-leukemia activity. Its antitumor mechanism involves cell cycle blockade, induction of apoptosis, and inhibition of tumor cell migration and invasion.

Anti-osteoporosis activity

Epimedium shows significant effects in regulating bone metabolism, promoting osteoblast differentiation and bone matrix formation, inhibiting osteoclast activity, thereby exerting anti-osteoporosis effects. Related targets include key bone formation transcription factors RUNX2, SP7 (Osterix), bone resorption-related enzyme CTSK (Cathepsin K), and signaling molecules regulating bone metabolism such as TNFRSF11B (OPG), SOST (bone scleroprotein), and COL1A1 (type I collagen). Additionally, epimedium further promotes bone health by regulating the vitamin D receptor (VDR) and estrogen receptor 1 (ESR1) signaling pathways.

Immunomodulatory and anti-inflammatory effects

Epimedium can regulate the expression of various inflammatory mediators, inhibit the release of pro-inflammatory cytokines, and reduce inflammatory responses. Its mechanism of action involves regulation of signaling pathways such as MAPK/ERK/JNK and JAK2/STAT3/AKT, promoting the maintenance of immune homeostasis.

Mechanism of action and molecular targets

The biological effects of epimedium mainly occur by regulating multiple cellular signaling pathways:

1. MAPK/ERK/JNK signaling pathway: Epimedium can activate or inhibit members of the MAPK family, regulating cell proliferation, differentiation, and apoptosis. In osteocytes, activation of ERK signaling promotes osteoblast differentiation, while regulation of JNK signaling helps suppress inflammatory responses.

2. JAK2/STAT3/AKT signaling pathway: This pathway plays a key role in cell survival, proliferation, and immune regulation. Epimedium inhibits JAK2 kinase activity, blocking STAT3 phosphorylation, thereby suppressing tumor cell proliferation and inflammatory responses. At the same time, it regulates the AKT signaling pathway and participates in bone metabolism regulation.

3. Nuclear receptor regulation: Epimedium binds to vitamin D receptors (VDR) and estrogen receptor 1 (ESR1), modulating the expression of bone metabolism-related genes, promoting bone formation, and inhibiting bone resorption.

4. Bone metabolism-related targets: Epimedium regulates the expression of key bone formation transcription factors RUNX2 and SP7, promoting osteoblast differentiation. By inhibiting osteoclastase CTSK and regulating bone metabolism regulators TNFRSF11B (OPG) and SOST, the dynamic balance of bone reconstruction is maintained.

Druggability evaluation and pharmacokinetics

Epimedium has a good medicinal foundation. Its molecular weight is moderate, and the LogP value shows pharmacokinetic characteristics suitable for lipophilic drugs. Although water-soluble is relatively low, formulation optimization can improve oral absorption. The blood-brain barrier has low permeability, reducing the risk of central nervous system side effects. hERG channel inhibition was negative, indicating higher cardiac safety. Ames test results showed that it carries a low genotoxicity risk and is safe.

Pharmacokinetic studies show that epimedium is absorbed quickly after oral administration, but its bioavailability is limited by its low water solubility and first-pass effect. In the body, it is mainly metabolized by the liver, whose metabolic products are mostly water-soluble compounds that facilitate excretion. Moderate half-life, suitable for daily administration. Further optimization of formulations and dosing regimens is needed in the future to enhance their clinical application potential.

Prospects and outlooks for clinical applications

As a natural flavonoid compound, epimedium shows broad application prospects in the fields of anti-osteoporosis, anti-tumor, and immune regulation due to its multi-target and multi-mechanism pharmacological properties. Especially in the prevention and treatment of osteoporosis, epimedium promotes both osteogenesis and inhibits bone breakdown, making it promising to become a safe and effective bone protector. Additionally, its inhibitory effect on chronic myeloid leukemia cells suggests its potential in adjuvant therapy for tumors.

However, clinical research on epimedium is still in its early stages, lacking systematic clinical trial data. Future research should focus on optimizing pharmacokinetics, developing dosage forms, and evaluating safety, conducting multicenter, randomized controlled clinical trials to verify efficacy and safety. At the same time, combining modern molecular biology techniques, the study deeply analyzes its mechanisms of action, uncovers more potential targets, and provides theoretical support for new drug development.

Conclusion

As an important active ingredient in epimedium, Epimedium has become a hot topic in natural product pharmacology research due to its unique chemical structure and diverse bioactivity. Its potential in anti-osteoporosis, anti-tumor, and immunomodulatory areas offers new ideas and possibilities for the treatment of related diseases. In the future, through in-depth mechanistic research and clinical validation, epimedium is expected to develop into a safe and effective natural drug or a novel drug lead compound, advancing the development of natural product drugs to a new level.