Product name: Wedelolactone
Synonym name: 5,11,12-Trihydroxy-7-methoxycoumestan
Catalogue No.: BP1451
Cas No.: 524-12-9
Formula: C₁₆H₁₀O₇
Mol Weight: 314.249
Botanical Source: EcliptaprostrataL.
Physical Description:
Type of Compound: Coumarins

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

Description:

​Wedelolactone is a potent Î2-arrestin-biased G protein-coupled receptor-35 (GPR35) agonist, GPR35 has been shown to be a target of the asthma drugs cromolyn disodium and nedocromil sodium. Wedelolactone has anti-inflammatory, growth inhibitory, anti-cancer, anti-fibrotic, and pro-apoptotic effects. Wedelolactone stimulates ER genomic and non-genomic signalling pathways; it can significantly inhibit the activation of LX-2 cells, the underlying mechanisms of which included inducing Bcl-2 family involved apoptosis, up-regulating phosphorylated status of ERK and JNK expressions, and inhibiting NF-κB mediated activity.

References:

J Ethnopharmacol. 2014 Nov 18;157:206-11.    

Inhibitory effect of Ecliptae herba extract and its component wedelolactone on pre-osteoclastic proliferation and differentiation.    

Ecliptae herba, also known as "Mo-Han-Lian", has long been used in China to nourish Kidney and thereafter strengthen bones. Accumulating evidence indicates that extracts of Ecliptae herba have antiosteoporotic effect. However, the effective compounds and cellular mode of action are still unclear. To investigate the effect of ethyl acetate extract of Ecliptae herba (EAE) and its component Wedelolactone on proliferation and differentiation of preosteoclastic RAW264.7 cells as well as proliferation of bone marrow stromal cells (BMSC). 

METHODS AND RESULTS:

RAW264.7 and BMSC were examined for proliferation by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method. Tartrate-resistant acid phosphatase (TRAP) activity of RAW264.7 was measured by using p-nitrophenyl sodium phosphate (pNPP) assay after the cells were treated with 30ng/ml receptor activator for nuclear factor-κ B ligand (RANKL) plus various concentrations of EAE, Wedelolactone or alendronate. The formation of multinucleated TRAP-positive RAW264.7 cells was observed by using a TRAP-staining kit. Treatment of RAW264.7 cells with EAE at high doses (20μg/ml and 40μg/ml) or Wedelolactone at 10μg/ml resulted in a decrease in proliferation of RAW264.7 cells. Low doses of EAE (5, 10μg/ml) and Wedelolactone(2.5μg/ml) inhibited RANKL-induced TRAP activity by 20.3%, 37.9%, and 48.3%. The inhibitory effect of Wedelolactone is more potent than that of alendronate, an anti-resorptive drug. Morphological changes revealed that 5μg/ml EAE and 2.5μg/ml Wedelolactone reduced the number of multinucleated osteoclast-like cells. At the high doses, EAE (20μg/ml) and Wedelolactone(10μg/ml) inhibited the growth of BMSC. 

CONCLUSIONS:

EAE and its component Wedelolactone inhibited osteoclast RAW264.7 proliferation and differentiation at the low doses, but at the high doses, showed cytotoxic effect on BMSC. These results indicated that EAE and wedelolatone might be potential alternative therapy for osteoporosis.    

J Cell Biochem. 2012 Nov;113(11):3436-45.    

Wedelolactone inhibits adipogenesis through the ERK pathway in human adipose tissue-derived mesenchymal stem cells.    

Wedelolactone is an herbal medicine that is used to treat septic shock, hepatitis and venom poisoning. Although in differentiated and cancer cells, Wedelolactone has been identified as anti-inflammatory, growth inhibitory, and pro-apoptotic, the effects of Wedelolactone on stem cell differentiation remain largely unknown. 

METHODS AND RESULTS:

Here, we report that Wedelolactone inhibits the adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells (hAMSCs). Wedelolactone reduced the formation of lipid droplets and the expression of adipogenesis-related proteins, such as CCAAT enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), lipoprotein lipase (LPL), and adipocyte fatty acid-binding protein aP2 (aP2). Wedelolactone mediated this process by sustaining ERK activity. In addition, inhibition of ERK activity with PD98059 resulted in reversion of the Wedelolactone-mediated inhibition of adipogenic differentiation. 

CONCLUSIONS:

Taken together, these results indicate that Wedelolactone inhibits adipogenic differentiation through ERK pathway and suggest a novel inhibitory effect of Wedelolactone on adipogenic differentiation in hAMSCs.    

Oncotarget. 2015 May 30;6(15):13049-59.    

Wedelolactone disrupts the interaction of EZH2-EED complex and inhibits PRC2-dependent cancer.   

Polycomb repressive complex 2 (PRC2), which is responsible for the trimethylation of H3K27 (H3K27me3), plays a part in tumorigenesis, development and/or maintenance of adult tissue specificity. The pivotal role of PRC2 in cancer makes it a therapeutic target for epigenetic cancer therapy. However, natural compounds targeting the enhancer of zeste homolog 2 (EZH2) - embryonic ectoderm development (EED) interaction to disable PRC2 complex are scarcely reported. 

METHODS AND RESULTS:

Here, we reported the screening and identification of natural compounds which could disrupt the EZH2-EED interaction. One of these compounds, Wedelolactone, binds to EED with a high affinity (KD = 2.82 μM), blocks the EZH2-EED interaction in vitro, induces the degradation of PRC2 core components and modulates the expression of detected PRC2 downstream targets and cancer-related genes. Furthermore, some PRC2-dependent cancer cells undergone growth arrest upon treatment with Wedelolactone. 

CONCLUSIONS:

Thus, Wedelolactone and its derivatives which target the EZH2-EED interaction could be candidates for the treatment of PRC2-dependent cancer.    

HPLC of Wedelolactone

HNMR of Wedelolactone

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

Introduction/Overview

Wedelolactone (CAS No.: 524-12-9) is a natural compound isolated from the traditional Chinese medicinal material Eclipta prostrata, belonging to the sesquiterpene lactone class. In recent years, with the deepening of pharmacological research on natural products, Rycocyglidoid has gradually attracted attention due to its multi-target and multi-pathway biological activity, especially showing significant potential in anti-inflammation, anti-tumor, and immunomodulatory fields. By directly inhibiting the IKK complex, it suppresses LPS-induced caspase-11 expression, demonstrating the ability to suppress inflammatory responses; At the same time, chrysanthemum lactone has a strong inhibitory effect on 5-lipoxygenase (5-LOX), with an IC50 of 2.5 μM. Additionally, this compound can downregulate the apoptosis of caspase-dependent prostate cancer cells induced by PKCε without affecting the Akt signaling pathway, demonstrating its unique mechanism of action in tumor cell regulation. This article will systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of Chrysantinolide, aiming to provide a theoretical foundation and reference for further research and development of this natural product.

Chemical structure and physicochemical properties

The molecular formula of Cyrus lactone is C17H14O6, with a molecular weight of 314.2490. Its structural features are the typical sesquiterpene lactone framework, containing multiple phenolic hydroxyl groups and lactone rings. Its LogP value was 2.5341, indicating that the compound has moderate lipid solubility, which facilitates cell membrane penetration and distribution in vivo. The polar surface area (TPSA) is 113.27 Ų, indicating limited solubility in polar environments. Low water solubility (0.0153 mg/mL) may limit its oral bioavailability. Low blood-brain barrier permeability suggests limited function 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 no significant mutagenicity and good safety.

In terms of chemical structure, the presence of phenolic hydroxyl groups confers antioxidant activity, while lactone rings are important structural groups for binding to target proteins. The structural polyhydroxyl and lactone rings enable Nysperulin to form hydrogen bonds and hydrophobic interactions with various enzymes and receptors, explaining the molecular basis of its multi-target pharmacological activity.

Plant Origins and Extraction Methods

Eclipta prostrata is mainly extracted from the traditional Chinese medicinal material Eclipta prostrata. Snakehead intestine belongs to the Asteraceae family, widely distributed in tropical and subtropical Asia, and has long been used to treat liver diseases, inflammation, and skin conditions. The whole plant contains various active ingredients, including flavonoids, terpenes, and lactones, among which Rycosin is one of the representative active ingredients.

The extraction method typically uses organic solvent extraction combined with column chromatography for separation. The specific steps include: crushing dried snakehead intestines, reflux extraction with ethanol or methanol, extracting the extract by concentration and separating it by silica gel column chromatography, and purifying chrysanololide using solvent systems of different polarities (such as ethyl acetate-methanol gradient elution). High-performance liquid chromatography (HPLC) and mass spectrometry (MS) technologies are used for purity detection and structural confirmation. In recent years, the application of ultrasound-assisted extraction and microwave-assisted extraction technologies has significantly improved extraction efficiency and purity, providing technical support for the large-scale preparation of Chrysolin.

Pharmacological activity research

The pharmacological activities of Chrysanolin encompass anti-inflammatory, anti-tumor, antioxidant, and immunomodulatory aspects.

1. Anti-inflammatory effects

Cyperanolactone directly inhibits the IKK complex, blocking activation of the NF-κB signaling pathway, significantly suppresses LPS-induced caspase-11 expression, and reduces inflammatory responses. Its inhibitory effect on 5-lipoxygenase (5-LOX) (IC50=2.5 μM) further suppresses the production of inflammatory mediators, demonstrating good anti-inflammatory effects. In vivo experiments, chrysanthemum lactone can lower levels of inflammatory factors such as TNF-α and IL-6, alleviating tissue damage caused by inflammation.

2. Antitumor effects

Cyrus lactone exhibits significant anti-proliferative and pro-apoptotic effects across various tumor models. By downregulating the caspase-dependent pathway induced by PKCε, it promotes apoptosis of prostate cancer cells without affecting the Akt signaling pathway, demonstrating the ability to selectively regulate tumor cell survival. In addition, Chrysanthemum can regulate various tumor-related targets, including MCL1, BCL2, STAT3, MMP2, TOP1, HIF1A, TOP2A, MAPK1, ESR1, and CYP19A1, participating in cell cycle regulation, apoptosis, invasion, and metastasis.

3. Antioxidant and immunomodulatory

The phenolic hydroxyl structure of chrysanthemum lactone endows it with excellent antioxidant capacity, which can eliminate free radicals and reduce oxidative stress damage. In terms of immune regulation, chrysanthemum lactone enhances immune function by modulating inflammatory factors and signaling pathways, demonstrating its potential immunomodulatory effects.

Mechanism of action and molecular targets

The pharmacological mechanisms of Cyrus lactone mainly involve the following aspects:

1. Inhibits the IKK/NF-κB signaling pathway

The IKK complex is a key kinase in the NF-κB signaling pathway, regulating inflammation and immune responses. Crag-chrysanthelide exerts anti-inflammatory effects by directly inhibiting IKK activity, blocking the phosphorylation and degradation of IκBα, and suppressing NF-κB nuclear translocation, thereby reducing the expression of inflammatory genes, especially the induction of caspase-11.

2. Inhibits 5-lipoxygenase (5-LOX)

5-LOX catalyzes fatty acid metabolism to produce leukotrienes, the inflammatory mediator; the inhibition of 5-LOX by Rycocythinolide blocks the production of inflammatory mediators, reducing inflammatory responses.

3. Regulates tumor-related signaling pathways

Cyperyl lactone activates caspase-dependent apoptotic pathways by downregulating PKCε, promoting tumor cell death. At the same time, this compound does not inhibit the Akt pathway, avoiding widespread interference with cell survival signaling and demonstrating good selectivity. In addition, cyrydallides can influence the expression of various tumor-associated proteins, such as anti-apoptotic proteins MCL1 and BCL2, transcription factor STAT3, matrix metalloproteinase MMP2, DNA topoisomerase TOP1/2A, hypoxia-inducible factors HIF1A, MAPK1, etc., comprehensively regulating tumor cell proliferation, migration, and invasion.

4. Other potential targets

Nymphalin may also influence the development of hormone-related tumors by modulating estrogen receptor (ESR1) and aromatase (CYP19A1) activity, suggesting its potential application value in hormone-dependent tumors such as breast cancer.

Druggability evaluation and pharmacokinetics

The druggability parameters of Rycolactone indicate that it has certain development potential. The molecular weight of 314.2490 conforms to the Lipinski rule, with a moderate LogP value of 2.5341, which is favorable for cell membrane penetration. Higher TPSA (113.27 Ų) and lower water solubility (0.0153 mg/mL) suggest that oral absorption may be limited, requiring pharmacological methods to improve solubility and bioavailability. The blood-brain barrier has low permeability, reducing the risk of central nervous system side effects. hERG channels have no inhibitory effect, indicating high cardiac safety. Ames test was negative, indicating low risk of mutagenic variance.

Currently, pharmacokinetic research on Chrysanolide is relatively limited. In vivo experiments have shown that after oral administration, effective concentrations can be detected in plasma, but bioavailability is low and half-life is moderate. Metabolic pathways mainly involve hepatic enzyme systems and may have a first-pass effect. In the future, further systematic pharmacokinetic studies are needed to clarify its absorption, distribution, metabolism, and excretion characteristics, providing a basis for clinical development.

Prospects and outlooks for clinical applications

As a multi-target natural product, Cyperic Cygmatoid has broad pharmacological activity and good safety, demonstrating potential for application in anti-inflammatory and anti-tumor fields. Its inhibitory effect on inflammatory signaling pathways gives it potential therapeutic value in chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. Its antitumor activity makes it possible for adjuvant therapy in prostate cancer, breast cancer, and other solid tumors.

However, the clinical translation of Chrysanolin faces many challenges, including low water solubility and limitations in oral bioavailability, incomplete pharmacokinetic properties, and a lack of systematic clinical safety and efficacy data. Future research should focus on:

1. Pharmaceutical improvements: Enhancing solubility and bioavailability through nanocarriers, solid dispersions, and other technologies.
2. Systematic pharmacokinetics and toxicology studies: clarifying their in vivo behavior and safety windows.
3. Preclinical animal model validation: Evaluate efficacy and mechanisms in inflammation and tumor models.
4. Clinical trial design: Conduct early clinical studies to verify safety and preliminary efficacy.

In addition, the design and synthesis of derivatives based on the structure of chrysantinoid and optimizing their pharmacodynamic and pharmacokinetic properties is also a key focus for future development.

Conclusion

As a natural product derived from traditional Chinese medicine, Craberrygedin, with its unique chemical structure and multi-target pharmacological activity, shows broad prospects for research and application. Its potential in anti-inflammatory and anti-tumor fields has been confirmed by multiple basic studies, but bottlenecks in druggability and clinical translation still need to be overcome. In the future, through in-depth mechanistic research, pharmaceutical improvements, and systematic clinical validation, Rydin is expected to become an important candidate molecule in the development of natural product drugs, providing new strategies and options for the treatment of related diseases.