Product name: 1,5-Dicaffeoylquinic acid
Synonym name: Cynarin; Cynarine
Catalogue No.: BP0006
Cas No.: 30964-13-7
Formula: C₂₅H₂₄O₁₂
Mol Weight: 516.455
Botanical Source: globe artichoke (Cynara scolymus), quince fruit (Cydonia oblonga), Caucasian whortleberry (Vaccinium arctostaphylos), Aster scaber and Ipomoea batatas (sweet potato) tubers
Physical Description:
Type of Compound: Phenylpropanoids

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, up to kilograms
Inquire for bulk scale.

Descriptions:
1,5-Dicaffeoylquinic acid (1,5-DQA), a caffeoylquinic acid derivative isolated from Aster scaber, has neuroprotective effects, can prevent Aβ(42)-induced neurotoxicity through the activation of PI3K/Akt followed by the stimulation of Trk A, then the inhibition of GSK3β as well as the modulation of Bcl-2/Bax.[1]
1,5-Dicaffeoylquinic acid has antioxidant activity, and is stronger than that of ascorbic acid.[2]
1,5-Dicaffeoylquinic Acid has protective effects against MPP~+ induces neurotoxicity of PC12 Cells, it (50 μmol/L) pretreatment can inhibit the MPP+-induced up-regulation of the expression of α-synuclein mRNA and protein.[3]
1, 5-Dicaffeoylquinic acid can mediate glutathione synthesis through activation of Nrf2 protects against OGD/reperfusion-induced oxidative stress in astrocytes.[4]

References:
[1] XIAO, Hai-bing, WANG, et al. Chinese Medl Jl, 2011, 124(17):2628-35.
[2] Slanina J, Paulová H, Humpa O, et al. Organic Chem, 1999, 72.
[3] Cao X, Xiao H, Li H. Acta Med Universit Sci Et Technol Huazhong, 2010, 39(4):435-38.
[4] Xu C, Xiao H, Zhang Y, et al. Brain Res, 2010, 1347(1):142-8.
[5] Dong Y, Zhang Y, Liu Y, et al. Chinese J Pharm, 2010, 41(6):447-9.

HPLC of 1,5-Dicaffeoylquinic acid

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

Introduction/Overview

1,5-Dicaffetoylquinine (Cynarine, CAS No.: 30964-13-7) is an important natural caffeitylquinic acid derivative, widely found in Asteraceae plants, especially medicinal plants such as artichoke (Cynara scolymus). As a polyphenolic compound, 1,5-dicaffeylquinic acid has attracted widespread attention in the field of natural product pharmacology in recent years due to its remarkable antioxidant activity and free radical scavenging ability. Numerous studies have shown that this compound shows promising potential in the prevention and treatment of cardiovascular diseases, especially atherosclerosis, involving multiple molecular targets and signaling pathways.

This paper aims to systematically review the chemical structure and physicochemical properties of 1,5-diacaffeylquinic acid, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation and pharmacokinetic characteristics, as well as its potential value in clinical applications, providing a theoretical basis and reference for subsequent related research.

Chemical structure and physicochemical properties

1,5-Dicaffeoylquinic acid is a derivative formed by two caffeoyl groups connected to a quinic acid molecule via ester bonds. Its molecular formula is C25H24O12, and its molecular weight is 516.4550. Structurally, the quinic acid backbone provides multiple hydroxyl sites, giving the molecule strong hydrophilicity and multihydroxyl characteristics.

In terms of physicochemical properties, the LogP value of 1,5-diacaffeylquinine acid is 1.2647, indicating moderate lipid solubility that facilitates cell membrane penetration. The polar surface area (TPSA) reaches as high as 211.28 Ų, reflecting strong molecular polarity, with a water solubility of 0.6256, indicating good solubility in the aqueous phase. Additionally, this compound has low blood-brain barrier penetration ability, negative results in hERG channel inhibition experiments, and zero in Ames mutagenicity tests, indicating high safety and a solid foundation for druggability.

Plant Origins and Extraction Methods

1,5-Dicaffetyl quinic acid is mainly found in Asteraceae plants, especially abundant in the leaves of artichoke (Cynara scolymus). In addition, some wild plants of the Asteraceae family and traditional medicinal plants have also been reported. This compound mostly exists in free or bound states within plants, with its content significantly affected by growth environment, harvest time, and processing method.

The extraction method mostly uses organic solvent extraction combined with liquid chromatography separation technology. Common extraction solvents include methanol, ethanol, and their aqueous solutions, which are used for ultrasonic-assisted extraction or reflux extraction to improve extraction efficiency. The extract is concentrated, liquid-liquid dispensed, and purified by silica gel column chromatography, with purity ultimately identified by high-performance liquid chromatography (HPLC) or mass spectrometry (MS). In recent years, supercritical CO2 extraction and membrane separation technologies have also been attempted to extract this compound, aiming to achieve efficient and green separation.

Pharmacological activity research

Antioxidant and free radical scavenging

1,5-Dicaffetoylquinic acid has significant antioxidant activity and can effectively scavenge various free radicals, including hydroxyl radicals (· OH), superoxide anion (O2·-), and hydrogen peroxide (H2O2). In vitro DPPH radical scavenging experiments and ABTS+ radical scavenging experiments both demonstrated concentration-dependent antioxidant capacity. Its antioxidant mechanism mainly relies on the action of multiple phenolic hydroxyl groups in the molecule as hydrogen donors, stabilizing free radicals and blocking lipid peroxidation chain reactions.

Anti-inflammatory effects

Inflammatory responses are the pathological basis of many chronic diseases. 1,5-Dicaffeylquinic acid demonstrates good anti-inflammatory effects by inhibiting pro-inflammatory cytokines (such as TNF-α, IL-6) and nuclear factor κB (NF-κB) signaling pathways. Cell experiments have shown that this compound can significantly reduce the expression of inflammatory mediators in macrophages, thereby alleviating inflammatory damage.

Cardiovascular protective effects

In the atherosclerosis model, 1,5-dicaffeylquinic acid exerts cardiovascular protection by regulating lipid metabolism, inhibiting vascular endothelial cell damage, and reducing oxidative stress. It can promote cholesterol reversal, increase high-density lipoprotein (HDL) function, reduce low-density lipoprotein (LDL) oxidation, and delay plaque formation.

Other pharmacological effects

In addition, preliminary research has also shown 1,5-dicaffeylquinic acid in liver protection, anti-tumor effects, and neuroprotection, demonstrating its multi-target, multi-mechanism pharmacological potential.

Mechanism of action and molecular targets

The mechanism of action of 1,5-dicaffetoylquinic acid in atherosclerosis and related diseases involves several key molecular targets:

• AMPK (PRKAA1): As a cellular energy sensor, AMPK activates to promote lipid metabolic balance and antioxidant defense. 1,5-Dicaffetoquinic acid can activate the AMPK signaling pathway, enhance cellular energy metabolism, and inhibit lipid accumulation.

• EHMT2 (EHMT2): a histone methyltransferase involved in gene expression regulation. This compound may influence the expression of inflammation- and metabolite-related genes by modulating EHMT2-mediated epigenetic modifications.

• MCL1 and BCL2: These two anti-apoptotic proteins play key roles in cell survival. 1,5-Dicaffetoylquinic acid regulates MCL1 and BCL2 expression to protect vascular endothelial cells from oxidative stress-induced apoptosis.

• RECQ1 :D NA helicase and participates in DNA repair. This compound may promote RECQ1 activity, enhancing the cell's ability to repair oxidative damage.

• LOX-1: Oxidizes low-density lipoprotein receptors and mediates the formation of atherosclerotic plaques. 1,5-Dicaffetoylquinic acid inhibits LOX-1 expression, reducing LDL oxidation and inflammatory responses.

• ABCA1: ATP-binding cassette transporter A1, a key cholesterol reverse transporter. This compound promotes ABCA1 expression, enhances cholesterol efflux, and prevents lipid deposition.

• IDO1: Indole amine 2,3-dioxygenase 1, involved in immune regulation. 1,5-Dicaffetoquinic acid may regulate IDO1 activity, modulate the immune environment, and reduce inflammation.

The synergistic effects of these targets form the multidimensional mechanism basis for the prevention and treatment of atherosclerosis.

Druggability evaluation and pharmacokinetics

The druggability parameters of 1,5-dicaffetoylquinic acid indicate good development potential. Moderate molecular weight (516.4550) and LogP (1.2647) facilitate in vivo distribution and cell membrane penetration. A high TPSA value (211.28 Ų) limited blood-brain barrier penetration but reduced the risk of central nervous system side effects. Water solubility is 0.6256, indicating a certain solubility in the aqueous phase, which is beneficial for the development of oral formulations.

In terms of safety, hERG channel inhibition was negative, reducing the risk of arrhythmias; Ames test was negative, indicating no obvious mutagenicity. Currently, there is limited research on in vivo pharmacokinetics, but preliminary data indicate that it is absorbed orally quickly, has moderate bioavailability, is mainly metabolized by the liver, and has diverse excretion pathways. Future evaluations of its metabolic enzyme involvement and drug interaction risks are needed in the future.

Prospects and outlooks for clinical applications

Given the multiple roles of 1,5-dicaffeylquinic acid in antioxidant, anti-inflammatory, and lipid metabolism regulation, it has broad application prospects in the prevention and treatment of atherosclerosis and related cardiovascular diseases. Currently, based on its natural origin and good safety, 1,5-dicaffeylquinic acid is regarded as an ideal candidate ingredient for functional foods, health supplements, and adjunctive therapeutic drugs.

Future clinical research should focus on its therapeutic dosage range, long-term safety, and its combined application with existing cardiovascular drugs. Moreover, by combining modern drug design technologies, structural optimization, and nanocarrier delivery, it is expected to enhance bioavailability and targetability, driving its translation into clinical drugs.

Conclusion

1,5-Dicaffetoquinic acid, as a natural caffetoylquinic acid derivative with significant antioxidant and free radical scavenging activities, demonstrates multi-target and multi-mechanism pharmacological activity, especially showing great potential in the prevention and treatment of atherosclerosis. Its excellent physicochemical properties and safety provide a solid foundation for druggability. With deeper elucidation of molecular mechanisms and advances in pharmacokinetic research, 1,5-dicaffeylquinic acid is expected to become an important research subject and application resource in the fields of natural product pharmacology and cardiovascular disease treatment. Future research needs to further integrate the multidisciplinary strengths of pharmacology, medicinal chemistry, and clinical medicine to promote its transition from the laboratory to clinical applications.