+86-28-82633987
Synonym name: Yejuhua lactone
Catalogue No.: BP0696
Cas No.: 62687-22-3
Formula: C32H40O8
Mol Weight: 552.664
Botanical Source: Handelia trichophylla and Chrysanthemum indicum
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:
Handelin has anti-inflammatory activity by inhibiting NF-κB activation and pro-inflammatory cytokine productions.
References:
Planta Med 2012; 78 - PD86.
Request full-text Anti-inflammatory activity of handelin through the modulation of NF-κB signaling and pro-inflammatory cytokine productions
Handelin, a guaianolide dimer, is a constituent of the flower of Chrysanthemum boreale Makino (Compositae). C. boreale have been used as traditional medicines for the treatment of vertigo and fever in Asian countries.
METHODS AND RESULTS:
The present study was designed to investigate the anti-inflammatory potential of Handelin in vitro and in vivo. Handelin inhibited LPS-stimulated production of NO and PGE2 in cultured mouse macrophage RAW 264.7 cells. The suppression of NO and PGE2 production by Handelin was correlated with the down-regulation of mRNA and protein expressions of iNOS and COX-2. Further study revealed that Handelin suppressed the induction of pro-inflammatory cytokines including TNF-α and IL-1β as well as microRNA-155 in LPS-induced RAW264.7 cells. Activation of the transcriptional activity of NF-κB by LPS was also alleviated by Handelin, which was well coincided with its inhibitory effect on IκB degradation. In addition, the activation of MAPKs such as ERK and JNK signaling was suppressed by Handelin. In in vivo animal model, oral administration of Handelin inhibited carrageenan-induced paw edema and TPA-induced ear edema, respectively. The analysis of cytokine production in serum showed that Handelin dose-dependently inhibited the production of IL-1β in a carrageenan-induced paw edema.
CONCLUSIONS:
These findings suggest that Handelin might be an active ingredient of C. boreale with the anti-inflammatory activity by inhibiting NF-κB activation and pro-inflammatory cytokine productions.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
119.3600
2.5036
2.5038
.0123
3.0186
4.1413
High
72.9055
7.0296
No
No
No
No
Yes
No
0.0
Yes
Yes
Yes
Yes
Handelin (CAS No.: 62687-22-3) is a guaiacol lactone dimer derived from the plant Chrysanthemum boreale, and has attracted widespread attention in recent years due to its remarkable anti-inflammatory activity. As the pathological basis of various diseases, inflammatory responses involve complex signaling pathways and cytokine networks. Finding highly effective natural anti-inflammatory drugs with low side effects has become an important direction for drug development. Wild chrysanthemum lactone demonstrates strong anti-inflammatory effects by regulating the nuclear factor κB (NF-κB) signaling pathway and the expression of various pro-inflammatory cytokines, offering potential clinical applications. This paper will systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and future clinical application prospects of wild chrysanthemum lactone, aiming to provide reference and guidance for research in the field of natural product pharmacology.
Wild chrysanthemum lactone is a dimer of guaiacol lactone with a complex molecular formula and a molecular weight of 552.6640. Its structural features include two guaiasoloid units connected by specific chemical bonds, forming a stable dimeric structure. The compound has a LogP of 2.5036, indicating moderate lipid solubility that facilitates cell membrane penetration. The polar surface area (TPSA) is 119.3600, indicating that it contains certain polar groups, which facilitate binding with biological macromolecules. Its low water solubility (0.0123) suggests limited solubility in the aqueous phase, but this can be improved to some extent through pharmaceutical formulation technology. Notably, wild chrysanthemum lactone has a high blood-brain barrier penetration ability, suggesting its potential role in anti-inflammatory treatment of central nervous system diseases. Additionally, the hERG channel inhibition test results were negative, indicating a low risk of cardiotoxicity; Ames mutagenic test results were 0.0, indicating low genotoxicity risk and good safety.
Wild chrysanthemum lactone mainly comes from the Asteraceae plant Chrysanthemum boreale, commonly known as wild chrysanthemum, a perennial herbaceous plant widely distributed throughout East Asia. In traditional Chinese medicine, this plant is used in traditional Chinese medicine for clearing heat, detoxifying, reducing inflammation, and relieving pain, with a long history of medicinal use. As one of its main active ingredients, wild chrysanthemum lactone is usually extracted and purified through the following steps:
Raw material collection and pretreatment
Collect the above-ground parts of wild chrysanthemums, dry them, and crush them into fine powder to facilitate solvent penetration.
Solvent extraction
Polar organic solvents such as ethanol or methanol are used for reflux extraction or ultrasound-assisted extraction to improve extraction efficiency.
Liquid-liquid separation and coarse separation
Through layered extraction of water and organic solvents, impurities are removed and target components are enriched.
Column chromatography purification
Using silica gel column chromatography or reversed-phase high-performance liquid chromatography (RP-HPLC) technology, wild chrysanthemum lactone is further purified to obtain high-purity compounds.
Structural appraisal
Compound structures are confirmed using technologies such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).
In recent years, with advances in extraction technology, supercritical fluid extraction and membrane separation techniques have also been introduced to improve extraction efficiency and purity, reduce the use of organic solvents, and align with the concept of green chemistry.
Pharmacological studies of wild chrysanthemum lactone mainly focus on its anti-inflammatory effects. Multiple in vitro and in vivo experiments have shown that wild chrysanthemum lactone can significantly inhibit inflammatory responses and reduce inflammation-related tissue damage.
In macrophage lines (such as RAW264.7 cells), wild chrysanthemum lactone can inhibit lipopolysaccharide (LPS)-induced production of pro-inflammatory factors, including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), nitric oxide synthase 2 (NOS2), and prostaglandin synthase 2 (PTGS2, COX-2). This compound exerts anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway, blocking the transcription of pro-inflammatory genes. In addition, wild chrysanthemum lactone can regulate the activity of the cell pyroptosis-related protein CASP1, reducing inflammatory cell death.
In various animal inflammation models, wild chrysanthemum lactone demonstrated good anti-inflammatory effects. For example, in mouse plantar swelling models and rat arthritis models, both oral or topical administration significantly reduced tissue edema and inflammatory cell infiltration, lowering levels of inflammatory mediators. Its anti-inflammatory effect is comparable to classic nonsteroidal anti-inflammatory drugs (NSAIDs), with fewer side effects.
In addition to its anti-inflammatory effects, wild chrysanthemum lactone is being explored for its potential applications in neuroinflammation and neurodegenerative diseases due to its excellent blood-brain barrier permeability. Additionally, some studies suggest it may possess multiple pharmacological activities such as antioxidant and antitumor properties, but the related mechanisms still need further clarification.
The anti-inflammatory mechanism of wild chrysanthemum lactone mainly regulates key inflammatory signaling pathways and targets, involving various cytokines and signaling molecules.
NF-κB is a core transcription factor in inflammatory responses, regulating the expression of various pro-inflammatory genes. Wild chrysanthemum lactone inhibits the activity of the IκB kinase (IKK) complex, blocking the phosphorylation and degradation of IκBα, thereby suppressing the relocation of NF-κB from the cytoplasm to the nucleus, reducing the expression of inflammatory factors such as TNF-α, IL-6, and PTGS2, thereby achieving anti-inflammatory effects.
Wild chrysanthemum lactone significantly downregulates the expression of pro-inflammatory factors such as IL-6, TNF, and NOS2, reducing the release of inflammatory mediators and alleviating inflammatory responses. In particular, inhibition of the IL-6/STAT3 signaling pathway helps block chronic inflammation and immune abnormalities.
By regulating CASP1 activity, wild chrysanthemum lactone reduces inflammatory cell death (pyroptosis) and protects tissue structural integrity. Additionally, wild chrysanthemum lactone modulates the TRPV1 and TRPA1 plasma channels, potentially affecting inflammation-related pain transmission and neuroinflammatory responses.
Wild chrysanthemolide also acts on PTGS1 (COX-1) and PTGS2 (COX-2), inhibiting prostaglandin synthesis and reducing inflammation and pain. Its regulation of the NFKB1 gene further enhances the multi-target characteristics of its anti-inflammatory mechanism.
In summary, wild chrysanthemum lactone demonstrates the potential for systematic regulation of inflammatory responses through multi-target and multi-pathway synergistic effects.
The molecular weight of wild chrysanthemum lactone is 552.6640, slightly above the 500 Da upper limit recommended by traditional oral drugs, but its LogP value (2.5036) is within the ideal range, indicating good lipophilubility and cell membrane permeability. TPSA is 119.3600, suitable for binding to biological targets while maintaining a certain degree of water solubility. Low water solubility (0.0123), which may limit oral absorption but can be improved through pharmacological methods.
Its high blood-brain barrier penetration capability offers possibilities for treating central nervous system inflammation. hERG is inhibited negative, and the Ames test shows no mutagenicity, indicating high safety and suitability for further development.
Currently, systematic pharmacokinetic research on wild chrysanthemum lactone is relatively limited. Preliminary in vivo experiments showed that wild chrysanthemum lactone was well absorbed orally and plasma concentrations reached effective levels. Its metabolism mainly occurs through hepatic enzyme systems, and its metabolites still require further identification. The main excretory routes are bile and urine.
In the future, more comprehensive ADME (Absorption, Distribution, Metabolism, Excretion) studies are needed to clarify its bioavailability, half-life, and potential drug interactions, providing scientific evidence for clinical application.
Wild chrysanthemum lactone, with its remarkable anti-inflammatory activity and good safety profile, has broad clinical application potential. It efficiently inhibits NF-κB and various pro-inflammatory factors, making it suitable for treating a wide range of inflammation-related diseases, including but not limited to:
In addition, the high blood-brain barrier permeability of wild chrysanololide provides new approaches for the treatment of neuroinflammation and neurodegenerative diseases. In the future, combining advanced pharmaceutical technologies such as nanocarriers and sustained-release formulations will further enhance its bioavailability and targeting.
However, clinical research on wild chrysanthemolide is still in its early stages, urgently requiring systematic preclinical safety evaluations and clinical trials to clarify its pharmacodynamics, toxicology, and dosage range. Optimizing its structure by integrating modern molecular pharmacology and medicinal chemistry to enhance its activity and pharmacokinetic performance will help drive its clinical adaptation.
Wild chrysanthemum lactone, a natural guaiacololide dimer derived from Chrysanthemum boreale, demonstrates excellent anti-inflammatory activity and good safety due to its multi-target ability to regulate inflammatory signaling pathways. Its unique chemical structure and physicochemical properties give it promising drug potential, especially promising applications in central nervous system inflammatory diseases. In the future, by deepening pharmacological mechanism research, improving pharmacokinetic data, and conducting clinical studies, wild chrysanthemum lactone is expected to become a new generation of safe and effective natural anti-inflammatory drugs, providing new strategies and options for the treatment of inflammatory diseases.
Shenshuai
Wenjing
Hedandan
