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℃
Handelin (CAS number: 62687-22-3) is a guaiacol lactone dimer derived from the plant Chrysanthemus Boreale, which has received widespread attention in recent years due to its significant anti-inflammatory activity. Inflammatory response, as the pathological basis of various diseases, involves complex signaling pathways and cytokine networks. Finding efficient and low side effect natural anti-inflammatory drugs has become an important direction for drug development. Wild chrysanthemum lactone exhibits strong anti-inflammatory effects by regulating the nuclear factor kappa B (NF - κ B) signaling pathway and the expression of various pro-inflammatory cytokines, and has potential clinical application value. This article provides a systematic review of the chemical structure, plant origin, pharmacological activity, mechanism of action, pharmacological evaluation, and future clinical application prospects of wild chrysanthemum lactone, aiming to provide reference and inspiration 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 guaiacol lactone units connected by specific chemical bonds to form a stable dimer structure. The LogP of this compound is 2.5036, indicating that it has moderate lipid solubility and is conducive to cell membrane penetration. The polar surface area (TPSA) is 119.3600, indicating that it has certain polar groups that are conducive to binding with biomolecules. Low water solubility (0.0123) suggests limited solubility in aqueous phase, but this can be improved to some extent through pharmaceutical formulation technology. It is worth noting that wild chrysanthemum lactone has a high blood-brain barrier permeability, indicating its potential role in anti-inflammatory treatment of central nervous system diseases. In addition, the hERG channel inhibition experiment showed a negative result, indicating a low risk of cardiac toxicity; The Ames mutagenicity test result is 0.0, indicating a low risk of genotoxicity and good safety.
Wild chrysanthemum lactone mainly comes from the Asteraceae plant Chrysanthemus Boreale, commonly known as wild chrysanthemum, which is a perennial herbaceous plant widely distributed in East Asia. This plant has a long history of medicinal use in traditional Chinese medicine for clearing heat, detoxifying, reducing inflammation, and relieving pain. Wild chrysanthemum lactone, as one of its main active ingredients, is usually extracted and purified through the following steps:
Raw material collection and pretreatment
Collect the aboveground parts of wild chrysanthemums, dry them and grind them into fine powder for easy solvent extraction and penetration.
Solvent extraction
Using polar organic solvents such as ethanol or methanol for reflux extraction or ultrasound assisted extraction to improve extraction efficiency.
Liquid liquid separation and crude separation
By layered extraction with water and organic solvents, impurities are removed and target components are enriched.
Column chromatography purification
Using silica gel column chromatography or reverse phase high-performance liquid chromatography (RP-HPLC) technology, further purification of wild chrysanthemum lactone is carried out to obtain high-purity compounds.
Structural Identification
The compound structure was confirmed using techniques such as nuclear magnetic resonance (NMR), mass spectrometry (MS), and infrared spectroscopy (IR).
In recent years, with the advancement of 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 comply with the concept of green chemistry.
The pharmacological research on wild chrysanthemum lactone mainly focuses on its anti-inflammatory effect. Multiple in vitro and in vivo experiments have shown that wild chrysanthemum lactone can significantly inhibit inflammatory responses and alleviate inflammation related tissue damage.
In macrophage cell lines such as RAW264.7 cells, wild chrysanthemum lactone can inhibit lipopolysaccharide (LPS) - induced pro-inflammatory cytokine production, including tumor necrosis factor alpha (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 the activation of the NF - κ B signaling pathway, blocking the transcription of pro-inflammatory genes. In addition, wild chrysanthemum lactone can regulate the activity of cell apoptosis related protein CASP1 and reduce inflammatory cell death.
In various animal inflammation models, wild chrysanthemum lactone has shown good anti-inflammatory effects. For example, in mouse paw swelling models and rat arthritis models, oral or local administration can significantly reduce tissue edema and inflammatory cell infiltration, and lower levels of inflammatory mediators. Its anti-inflammatory effect is comparable to classical nonsteroidal anti-inflammatory drugs (NSAIDs), and its side effects are relatively small.
In addition to its anti-inflammatory effects, wild chrysanthemum lactone is being explored for potential applications in neuroinflammation and neurodegenerative diseases due to its excellent blood-brain barrier permeability. In addition, some studies suggest that it may have multiple pharmacological activities such as antioxidant and anti-tumor effects, but the relevant mechanisms still need further clarification.
The anti-inflammatory mechanism of wild chrysanthemum lactone is mainly achieved by regulating key inflammatory signaling pathways and targets, involving various cytokines and signaling molecules.
NF - κ B is the core transcription factor of inflammatory response, regulating the expression of various pro-inflammatory genes. Wild chrysanthemum lactone inhibits the activity of I κ B kinase (IKK) complex, preventing the phosphorylation and degradation of I κ B α, thereby inhibiting the translocation of NF - κ B from cytoplasm to nucleus, reducing the expression of inflammatory factors such as TNF - α, IL-6, PTGS2, and achieving anti-inflammatory effects.
Wild chrysanthemum lactone significantly downregulates the expression of pro-inflammatory factors such as IL-6, TNF, and NOS2, reduces the release of inflammatory mediators, and alleviates inflammatory responses. Especially the inhibition of the IL-6/STAT3 signaling pathway helps to block chronic inflammation and immune abnormalities.
By regulating CASP1 activity, wild chrysanthemum lactone reduces inflammatory cell death (pyroptosis) and protects tissue structural integrity. In addition, wild chrysanthemum lactone has a regulatory effect on TRPV1 and TRPA1 plasma channels, which may affect inflammation related pain transmission and neuroinflammatory responses.
Wild chrysanthemum lactone 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 its multi-target properties in anti-inflammatory mechanisms.
In summary, wild chrysanthemum lactone exhibits the potential to systematically regulate inflammatory responses through multi-target and multi pathway synergistic effects.
The molecular weight of wild chrysanthemum lactone is 552.6640, slightly higher than the recommended upper limit of 500 Da for traditional oral drugs, but its LogP value (2.5036) is within the ideal range, indicating its good lipid solubility and cell membrane permeability. The TPSA is 119.3600, which is suitable for binding to biological targets while also considering a certain degree of water solubility. Low water solubility (0.0123) may limit its oral absorption, but it can be improved through pharmacological means.
Its high blood-brain barrier permeability provides the possibility for treating central nervous system inflammation. HERG inhibition was negative and Ames test showed no mutagenicity, indicating its high safety and suitability for further development.
At present, there is limited systematic pharmacokinetic research on wild chrysanthemum lactone. Preliminary in vivo experiments have shown that wild chrysanthemum lactone is well absorbed after oral administration, and the plasma concentration can reach an effective level. Its metabolism is mainly through the liver enzyme system, and the metabolites need to be further identified. The main excretion pathways are bile and urine.
In the future, more comprehensive research on ADME (absorption, distribution, metabolism, excretion) is needed to clarify its bioavailability, half-life, and potential drug interactions, providing scientific basis for clinical applications.
Wild chrysanthemum lactone has broad clinical application potential due to its significant anti-inflammatory activity and good safety. It efficiently inhibits NF - κ B and various pro-inflammatory factors, and is suitable for the treatment of various inflammation related diseases, including but not limited to:
In addition, the high blood-brain barrier permeability of wild chrysanthemum lactone provides new ideas for the treatment of neuroinflammation and neurodegenerative diseases. In the future, the combination of advanced pharmaceutical technologies such as nanocarriers and sustained-release formulations will further enhance their bioavailability and targeting.
However, the clinical research on wild chrysanthemum lactone is still in its infancy, and there is an urgent need to conduct systematic preclinical safety evaluations and clinical trials to clarify its pharmacodynamics, toxicology, and dosage range. Combining modern molecular pharmacology and medicinal chemistry to optimize its structure, enhance its activity and pharmacokinetic performance, will help promote its clinical translation.
Wild chrysanthemum lactone, as a natural guaiacol lactone dimer derived from Chrysanthemus Boreale, exhibits excellent anti-inflammatory activity and good safety due to its ability to regulate inflammatory signaling pathways through multiple targets. Its unique chemical structure and physicochemical properties endow it with excellent drug potential, especially its promising application prospects 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 choices for the treatment of inflammatory diseases.
