Product name: Cyclobisdemethoxycurcumin
Synonym name: 2,3-Dihydro-2-(4-hydroxyphenyl)-6-[(1E)-2-(4-hydroxyphenyl)ethenyl]-4H-pyran-4-one
Catalogue No.: BP5071
Cas No.: 1042441-12-2
Formula: C₁₉H₁₆O₄
Mol Weight: 308.333
Botanical Source:
Type of Compound: Phenols

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.

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

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

Introduction/Overview

Cyclobisdemethoxycurcumin (CBDMC), CAS number 1042441-12-2, is a natural compound derived from curcumins, and has attracted significant attention in recent years for its remarkable antioxidant and anti-inflammatory properties. Curcumin and its derivatives, as important candidate molecules in both traditional Chinese medicine and modern drug development, have become a hot topic in natural product pharmacology research due to their multi-target regulation and relatively low side effects. CBDMC, as a derivative of cyclic desmethoxycurcumin, has a unique structure, excellent bioactivity, and good druggability. This paper will systematically review the chemical structure and physicochemical properties of CBDMC, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, and, combined with its anti-inflammatory targets, explore its potential and challenges for future clinical application.

Chemical structure and physicochemical properties

Didesmethoxycyclocurcumin is a cyclic dimer structure with the molecular formula C18H16O5 and a molecular weight of 308.3330. Its structural feature is that two desmethoxy-curtin units are connected by cyclization, forming a stable cyclic configuration that imparts unique chemical and biological activity. Its LogP value is 2.9734, indicating moderate lipid solubility, which is beneficial for cell membrane permeability and distribution in vivo. TPSA (Topological Polar Surface Area) is 66.7600, indicating moderate polarity, which is beneficial for binding with biological macromolecules and transmembrane transport.

Low water solubility (0.0714 mg/mL) suggests limited solubility in the aqueous phase, which may affect oral bioavailability. Notably, CBDMC has a high blood-brain barrier penetration capability, suggesting its potential application value in central nervous system diseases. Additionally, the hERG channel inhibition test results were negative, indicating a low cardiotoxicity risk, while the Ames mutagenicity test was 0.0, indicating low genotoxicity risk and good safety.

Plant Origins and Extraction Methods

Bisdemethoxycyclocurcumin mainly comes from the rhizomes of ginger plants such as curcuma longa L. Curcumin compounds are the main bioactive components in turmeric. Traditional extraction mostly uses ethanol or methanol as solvents, and crude extracts are obtained by methods such as ultrasound-assisted extraction, Soxhlet extraction, or pressurized liquid extraction. Subsequently, high-performance liquid chromatography (HPLC), column chromatography, and counterflow chromatography were used for separation and purification, ultimately yielding high-purity CBDMC.

In recent years, green extraction technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been applied to the extraction of curcumin compounds, improving extraction efficiency and reducing the use of organic solvents, aligning with the environmental trend of modern natural product extraction. During purification, analytical methods such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) are used to ensure accurate identification of compound structures.

Pharmacological activity research

Antioxidant activity

CBDMC exhibits significant antioxidant capacity. In DPPH radical scavenging tests, its IC50 is about 250 μM, indicating it has good radical scavenging ability. More notably, in the 2-deoxyribose (2-DR) oxidation test, the IC50 of CBDMC was only 15-20 μM, indicating strong protection against DNA damage induced by hydroxyl radicals. This antioxidant activity may be related to its phenolic hydroxyl structure and cyclic configuration as a stabilizing free radical intermediate.

Anti-inflammatory activity

CBDMC has demonstrated significant anti-inflammatory effects across various in vitro and in vivo models. It is mainly achieved by regulating various inflammation-related signaling pathways and targets, including key molecules such as IL-6, STAT3, CASP1, TRPV1, PTGS1, TNF, TRPA1, NOS2, PTGS2, and NFKB1. Research shows that CBDMC can inhibit the expression of pro-inflammatory cytokines, reduce the release of inflammatory mediators, and suppress the activation and migration of inflammatory cells, thereby alleviating inflammatory responses.

Additionally, CBDMC inhibits inflammation-related enzymes such as cyclooxygenase (PTGS1 and PTGS2) and induced nitric oxide synthase (NOS2), reducing the production of prostaglandins and nitric oxide to further alleviate inflammation. Its inhibitory effect on the NFKB1 signaling pathway blocks transcriptional activation of inflammatory genes, exerting multi-target synergistic anti-inflammatory effects.

Other potential activities

Although current research on CBDMC mainly focuses on antioxidant and anti-inflammatory fields, its high blood-brain barrier permeability suggests its potential applications in neuroprotection, anti-tumor treatment, and metabolic disease protection. Future related research is expected to further expand its pharmacological spectrum.

Mechanism of action and molecular targets

The mechanism of action of CBDMC mainly involves regulating various inflammatory and oxidative stress-related signaling pathways:

1. IL-6/STAT3 signaling pathway: IL-6 acts as a pro-inflammatory cytokine that promotes the expression of inflammatory genes by activating the STAT3 transcription factor. CBDMC can inhibit IL-6 secretion and STAT3 phosphorylation, blocking the transmission of inflammatory signals and reducing inflammatory responses.

2. CASP1 (Caspase-1): As a key enzyme for activating inflammasomes, CASP1 promotes the maturation and release of pro-inflammatory factors such as IL-1β. CBDMC inhibits CASP1 activity and blocks inflammatory cascades mediated by inflammasomes.

3. TRPV1 and TRPA1 channels: These two transient receptor potential channels play important roles in inflammatory pain and neuroinflammation. CBDMC alleviates inflammation-related pain and neuroexcitability by modulating the activity of TRPV1 and TRPA1.

4. PTGS1/PTGS2 (COX-1/COX-2): As key enzymes in prostaglandin synthesis, PTGS1 and PTGS2 are involved in the production of inflammatory mediators. CBDMC inhibits its activity and reduces the production of pro-inflammatory prostaglandins.

5. TNF-α: As a major pro-inflammatory cytokine, TNF-α plays a central role in various inflammatory diseases. CBDMC reduces the expression of TNF-α and alleviates inflammatory processes.

6. NOS2 (Induced Nitric Oxide Synthase): NOS2 produces large amounts of nitric oxide, which is involved in inflammation and oxidative stress. CBDMC inhibits NOS2 expression and reduces oxidative damage.

7. NFKB1: As a key transcription factor for inflammatory signals, NFKB1 regulates the expression of various inflammatory genes. CBDMC blocks the transcription of inflammatory genes by inhibiting NFKB1 activation.

In summary, CBDMC leverages its anti-inflammatory and antioxidant pharmacological effects through multi-target and multi-pathway synergistic effects, demonstrating the advantages of multi-target regulation of natural products.

Druggability evaluation and pharmacokinetics

The druggability evaluation of CBDMC shows it has promising potential for drug development:

• The molecular weight (308.3330) complies with the Lipinski rule and is beneficial for oral absorption.
• LogP (2.9734) is moderate, indicating good lipid solubility, which facilitates cell membrane penetration.
• TPSA (66.7600) is moderate, supporting good oral bioavailability and cell uptake.
• Water solubility (0.0714 mg/mL) is relatively low, suggesting that formulation technology is needed to improve solubility to enhance bioavailability.
• The high permeability of the blood-brain barrier opens up its potential for applications in central nervous system diseases.
• No hERG channel suppression, reducing the risk of cardiotoxicity.
• Ames mutagenicity test was negative, indicating relatively high safety.

Pharmacokinetics, although data on in vivo metabolism and excretion of CBDMC are currently limited, its structural stability and lipid solubility suggest it has good distribution characteristics in vivo. In the future, further in vivo pharmacokinetic studies are needed to clarify its absorption, distribution, metabolism, and excretion (ADME) characteristics, providing a basis for clinical translation.

Prospects and outlooks for clinical applications

Based on CBDMC's excellent antioxidant and anti-inflammatory activities, as well as its favorable druggability parameters, its application prospects in various inflammation-related diseases are broad. Specifically, it includes:

• Chronic inflammatory diseases: such as rheumatoid arthritis, inflammatory bowel disease, and chronic obstructive pulmonary disease. CBDMC suppresses inflammatory responses through multiple targets and is expected to become an effective adjunct therapy.
• Neuroinflammation and neurodegenerative diseases: Its high blood-brain barrier penetration supports its potential applications in neurological diseases such as Alzheimer's and Parkinson's, alleviating neuroinflammation and oxidative stress.
• Metabolic syndrome and cardiovascular diseases: By inhibiting inflammatory mediators and oxidative damage, CBDMC may improve metabolic abnormalities and cardiovascular function.
• Cancer adjuvant therapy: Inflammation is closely related to the tumor microenvironment, and the anti-inflammatory and antioxidant properties of CBDMC provide a theoretical basis for its adjunctive application in tumor treatment.

Future research should focus on in vivo pharmacokinetics, toxicological evaluation, and preclinical model validation of CBDMC, combined with modern pharmaceutical technologies such as nanoformulations and sustained-release systems to enhance bioavailability and targetability. At the same time, in-depth research on mechanisms was conducted to clarify their functional networks across different disease models, laying a solid foundation for clinical translation.

Conclusion

Bisdemethoxycyclocurcumin, as a structurally unique natural product, exhibits excellent antioxidant and anti-inflammatory activities, along with good druggability and safety characteristics. Its multi-target and multi-pathway mechanism provides solid scientific evidence for its application in inflammation and related diseases. Although current research on CBDMC is still in its early stages, its broad application prospects and potential clinical value warrant further exploration. In the future, systematic pharmacokinetics, toxicology, and preclinical research are expected to promote the translation of CBDMC into clinical drugs, enrich research achievements in the field of natural product pharmacology, and benefit human health.