Product name: 1,4-Dicaffeoylquinic acid
Synonym name:
Catalogue No.: BP1860
Cas No.: 1182-34-9
Formula: C₂₅H₂₄O₁₂
Mol Weight: 516.455
Botanical Source: Lonicera japonica Thunb.
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
Inquire for bulk scale.

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

HPLC of 1,4-Dicaffeoylquinic acid

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

Introduction/Overview

Natural products, as the source of drug discovery, play an irreplaceable role in the long struggle between humans and diseases. Among numerous natural compounds with biological activity, Caffeoylquinic acids (CQAs) and their derivatives have attracted much attention due to their widespread presence in daily diets (such as coffee, fruits, vegetables) and various medicinal plants, and their diverse pharmacological activities. 1,4-dicaffeoylquinic acid (1,4-dicaffeoylquinic acid, 1,4-diCQA), as an important member of the dicaffeoylquinic acid family, has a unique chemical structure and significant biological activity, especially in the field of antiviral research, making it a hot spot in natural product pharmacology research.

1,4-Dicaffeoylquinic acid, also known as 1,4-di-O-caffeoylquinic acid, is a phenolic acid compound formed by the ester bond between one molecule of quinic acid and two molecules of caffeic acid. Its structural feature is that the caffeoyl group is connected to the hydroxyl groups at positions 1 and 4 of quinic acid, respectively. This specific acylation mode endows it with unique physicochemical properties and biological activity profiles that differ from monocaffeoylquinic acid (such as chlorogenic acid) or other positional isomers (such as 3,5-dicaffeoylquinic acid).

From a historical perspective, the research on caffeoylquinic acid compounds can be traced back to the discovery of chlorogenic acid in the 19th century. However, the in-depth exploration of dicaffeoylquinic acid, especially its antiviral activity, accelerated in the 1980s and 1990s with the global spread of the human immunodeficiency virus (HIV). Early research found that certain plant extracts, such as those from honeysuckle（Lonicera japonica）The components isolated from Asteraceae plants have the ability to inhibit HIV reverse transcriptase and integrase activity. Subsequent chemical and pharmacological studies have confirmed that 1,4-dicaffeoylquinic acid is one of the key contributors to these activities.

This review aims to comprehensively and systematically review the research progress of 1,4-dicaffeoylquinic acid. The article will explore its plant origin and extraction techniques based on its chemical structure and physicochemical properties, with a focus on its pharmacological activity in the field of anti HIV and other diseases. It will also delve into its molecular mechanisms of action with key targets such as CCR5, CXCR4, HIV integrase, Nef, and Tat proteins. At the same time, combining modern medicinal chemistry and pharmacokinetic theory, objectively evaluate its drug properties, and look forward to its potential applications and challenges in clinical translation. Through this article, we hope to provide a comprehensive and in-depth reference for researchers engaged in natural product chemistry, pharmacology, and antiviral drug development.

Chemical structure and physicochemical properties

The chemical structure of 1,4-dicaffeoylquinic acid is the basis of all its biological activities. Its core skeleton is Quinic acid, a cyclohexane polyhydroxy acid containing four hydroxyl groups and one carboxyl group. In 1,4-dicaffeoylquinic acid molecules, the 1st and 4th hydroxyl groups of quinic acid are respectively connected to a molecule of caffeic acid through ester bonds. Caffeic acid is a hydroxycinnamic acid, which contains a catechol (catechol) group and an acrylic side chain in its structure. Therefore, 1,4-dicaffeoylquinic acid molecules are rich in phenolic hydroxyl groups and conjugated double bond systems, which are key structural units for their antioxidant properties, chelation of metal ions, and interactions with biomolecules.

From a stereochemical perspective, multiple chiral centers on the quinic acid ring endow the molecule with a specific three-dimensional conformation. There are spatial structural differences between 1,4-dicaffeoylquinic acid and its isomers, such as 3,4-3,5- and 4,5-dicaffeoylquinic acid. This difference directly affects their binding affinity and selectivity with different target proteins. For example, studies have shown that 3,5-dicaffeoylquinic acid has stronger inhibitory activity against HIV integrase, while 1,4-dicaffeoylquinic acid exhibits unique advantages in inhibiting HIV entry, attributed to its specific acyl spatial arrangement.

In terms of physicochemical properties, 1,4-dicaffeoylquinic acid exhibits typical phenolic acid compound characteristics. Its molecular weight is 516.4550 g/mol. According to computer-aided prediction, its lipid water partition coefficient (LogP) is 1.1817, indicating a certain degree of lipophilicity, but overall leaning towards hydrophilicity. The topologically polar surface area (TPSA) is as high as 211.2800 Å ², mainly attributed to the large number of hydroxyl and carboxyl groups in the molecule. A high TPSA value usually indicates that the molecule has good water solubility (predicted water solubility of 0.5847 mg/mL), but it also means that its transmembrane permeability is poor, especially difficult to penetrate the blood-brain barrier (predicted blood-brain barrier permeability is low). This characteristic determines its distribution and pharmacokinetic behavior in the body. In addition, the presence of phenolic hydroxyl groups makes it weakly acidic, easily dissociated under alkaline conditions, and relatively stable under acidic conditions. Its UV absorption spectral characteristics mainly come from the conjugated system of caffeoyl groups, usually with a strong absorption peak around 325 nm, which provides convenience for its detection and quantitative analysis.

Plant sources and extraction methods

1,4-Dicaffeoylquinic acid is widely distributed in nature, but it is not the main secondary metabolite, and its content is usually lower than the common chlorogenic acid (3-caffeoylquinic acid). It mainly exists in plants such as Asteraceae, Caprifoliaceae, Convolvulaceae, etc.

The main sources of plants include:
1. Honeysuckle flower（Lonicera japonica Thunb.）As a traditional Chinese medicine for clearing heat and detoxifying, honeysuckle is one of the most extensively studied sources of 1,4-dicaffeoylquinic acid. Its flower buds are rich in various caffeoylquinic acid compounds, among which 1,4-dicaffeoylquinic acid is one of the active ingredients.
2. Asteraceae plants Various Asteraceae plants, such as Artemisia argyi（Artemisia argyi）Artemisia scoparia, Artemisia scoparia（Artemisia capillaris）Stevia rebaudiana（Stevia rebaudiana）Purple cone chrysanthemum（Echinacea purpurea）All of them have been reported to contain 1,4-dicaffeoylquinic acid.
3. Coffee plants Although coffee beans mainly contain chlorogenic acid, trace amounts of dicaffeoylquinic acid, including 1,4-isomers, can also be detected in the leaves and fruits of coffee.
4. Other plants Like burdock（Arctium lappa）Dandelion（Taraxacum officinale）This compound also exists in common medicinal and edible plants.

The choice of extraction method is directly related to the yield, purity, and activity maintenance of the target compound. Given that 1,4-dicaffeoylquinic acid is sensitive to heat and light and easily oxidized, the extraction process typically requires mild conditions.

Traditional extraction methods：
- Solvent extraction method The most commonly used method. Usually, ethanol water or methanol water mixed solvents (such as 50% -80% ethanol) are used for heating reflux or cold soaking extraction. Acidizing solvents (such as adding a small amount of formic acid or acetic acid) can help improve the extraction efficiency of phenolic compounds and inhibit their dissociation. This method is simple to operate, but has poor selectivity, and the extract contains a large amount of impurities.
- Water extraction method Low cost, but the extraction efficiency is usually lower than that of alcohol extraction, and it is easy to introduce a large amount of water-soluble impurities such as polysaccharides and proteins.

Modern extraction and purification techniques：
- Ultrasound assisted extraction (UAE)Using the cavitation effect of ultrasound to destroy plant cell walls, accelerate solvent penetration and target component dissolution. This method has the advantages of short extraction time, low temperature, and high efficiency, and is particularly suitable for thermosensitive components.
- Microwave assisted extraction (MAE)By using microwave energy to selectively heat polar molecules (such as water), the interior of the cell rapidly heats up, increasing pressure and causing cell rupture, thereby releasing its contents. High efficiency, but attention should be paid to temperature control to prevent compound degradation.
- Enzyme Assisted Extraction (EAE)Using cellulases, pectinases, and other enzymes to hydrolyze plant cell walls, breaking down their structural barriers, thereby increasing the dissolution rate of target components. This method has mild conditions and is environmentally friendly, but the cost is relatively high.

Purification strategy：
The content of 1,4-dicaffeoylquinic acid in crude extract is usually low and requires further separation and purification.
- Liquid-liquid extraction Preliminary separation of target substances and impurities based on differences in solubility using different solvents such as ethyl acetate and n-butanol.
- Macroporous adsorption resin chromatography This is a classic method for separating and purifying phenolic acid compounds. By selecting appropriate types of resins (such as HPD-100, AB-8) and gradient elution conditions (ethanol water), the target components can be effectively enriched.
- Preparation type high performance liquid chromatography (Prep HPLC): is the most effective means to obtain high-purity (>98%) 1,4-dicaffeoylquinic acid. Usually, a reverse phase C18 chromatographic column is used, with acetonitrile water (containing a small amount of acid) as the mobile phase for isocratic or gradient elution.

Pharmacological activity research

The pharmacological activity research of 1,4-dicaffeoylquinic acid mainly focuses on its antiviral, antioxidant, anti-inflammatory and other aspects, among which the anti HIV activity is the most concerned core area.

Anti HIV activity

This is the most representative pharmacological activity of 1,4-dicaffeoylquinic acid. Numerous in vitro studies have shown that this compound can act on multiple stages of the HIV lifecycle, exhibiting multi-target inhibition properties.

1. Inhibiting the entry of HIV The entry of HIV into host cells requires its envelope glycoprotein gp120 to first bind to the CD4 receptor on the cell surface, and then interact with the co receptors CCR5 or CXCR4. 1,4-Dicaffeoylquinic acid has been shown to directly bind to gp120, inducing conformational changes and thereby blocking the binding of gp120 to CD4 and/or co receptors. More importantly, it can directly bind to CCR5 and CXCR4 receptors, acting as an antagonist of these chemokine receptors and preventing the virus cell membrane fusion process. This dual mechanism of action (targeting the viral envelope and host receptor) gives it a unique advantage in anti HIV entry inhibitors.
2. Inhibition of HIV integrase (IN)HIV integrase is responsible for integrating viral cDNA into the host cell genome and is an essential enzyme for viral replication. 1,4-Dicaffeoylquinic acid can inhibit the chain transfer and 3 'end processing activity of integrase. Its mechanism of action is believed to be that the catechol groups in its molecule can chelate divalent metal ions (such as Mg ² ⁺) required for the active site of integrase, thereby interfering with the function of the enzyme. In addition, it may also bind to specific amino acid residues of integrase proteins, forming non competitive inhibition.
3. Inhibition of HIV regulatory proteins：
   • Nef protein Nef protein plays a crucial role in maintaining high viral titer replication and immune escape. Research has shown that 1,4-dicaffeoylquinic acid can inhibit Nef mediated downregulation of MHC-I molecules, potentially restoring the ability of infected cells to be recognized and cleared by the immune system.
   • Tat protein Tat protein is a trans activator of HIV transcription and is crucial for viral gene expression. 1,4-Dicaffeoylquinic acid can inhibit the activity of Tat protein, possibly by interfering with the binding of Tat to TAR RNA elements, thereby inhibiting the initiation and extension of viral transcription.

Other pharmacological activities

1. antioxidant activity As a polyphenolic compound, 1,4-dicaffeoylquinic acid is an effective free radical scavenger and metal ion chelating agent. The catechol structure in its molecule can provide hydrogen atoms, neutralize reactive oxygen species (ROS) and reactive nitrogen species (RNS), thereby protecting cells from oxidative stress damage. Its antioxidant capacity is usually stronger than that of mono caffeoylquinic acid (such as chlorogenic acid).
2. anti-inflammatory activity 1,4-Dicaffeoylquinic acid can inhibit the production of various pro-inflammatory mediators, such as by suppressing the nuclear factor kappa B (NF - κ B) signaling pathway, reducing the release of tumor necrosis factor alpha (TNF - α), interleukin-6 (IL-6), and nitric oxide (NO). This is closely related to its antioxidant activity, as oxidative stress is an important driving factor in inflammatory responses.
3. Hepatoprotective activity In various liver injury models, 1,4-dicaffeoylquinic acid exhibits a protective effect. The mechanism may involve antioxidant, anti-inflammatory, and inhibition of hepatic stellate cell activation, thereby reducing liver fibrosis.
4. Antidiabetic activity Some studies have shown that 1,4-dicaffeoylquinic acid can inhibit alpha glucosidase activity, delay carbohydrate absorption, and thus help control postprandial blood sugar. In addition, it may play an anti diabetes role by improving insulin sensitivity.
5. Antibacterial activity It also exhibits certain inhibitory effects on certain bacteria and fungi, but its antibacterial spectrum and efficacy are usually weaker than specialized antibiotics.

Mechanism of action and molecular targets

The pharmacological activity of 1,4-dicaffeoylquinic acid originates from its interactions with multiple molecular targets, exhibiting typical "multi-target drug" characteristics. Its core mechanism of action can be summarized as follows:

1. Multi target mechanism of anti HIV therapy

This is the area where its research is most in-depth and its mechanism is most clear.

• Target: CCR5 and CXCR4 chemokine receptors
• mechanism 1,4-Dicaffeoylquinic acid binds to the extracellular loop or transmembrane domain of CCR5 and CXCR4 receptors through its caffeoyl and quinic acid backbone in its molecule. This binding may induce conformational changes in the receptor, making it unable to be recognized and bound by HIV gp120, thereby blocking virus entry. Molecular docking and mutation studies suggest that its binding site to CCR5 may overlap or have allosteric effects with the binding site of natural chemokines (such as MIP-1 α) or small molecule antagonists (such as Maraviroc).

• meaning Targeting two main HIV co receptors simultaneously theoretically can cover a wider range of viral preferences (R5 and X4 viruses), overcoming the problem of viral preference switching that may be caused by single co receptor antagonists.

• Target: HIV-1 gp120 envelope glycoprotein

• mechanism 1,4-Dicaffeoylquinic acid can directly bind to the conserved region of gp120, especially near the CD4 binding site or co receptor binding site. This binding stabilizes the closed conformation of gp120, preventing it from undergoing necessary conformational rearrangements after binding to CD4, thereby failing to expose the co receptor binding site and ultimately inhibiting membrane fusion. The surface plasmon resonance (SPR) experiment confirmed its direct binding with gp120.

• Target: HIV-1 integrase (IN)

• mechanism The mechanism by which it inhibits integrase activity is believed to be a dual effect of "metal ion chelation" and "protein binding". The catechol group in the molecule is an efficient metal chelating agent that can competitively capture the Mg ² ⁺ cofactor of the integrase active site (near the LEDGF/p75 binding pocket), thereby inhibiting the catalytic activity of the enzyme. In addition, it may also directly form hydrogen bonds or π - π stacking with amino acid residues of integrases (such as Lys, Arg), interfering with their binding to viral DNA substrates.

• Target: Nef and Tat regulatory proteins

• mechanism For Nef, 1,4-dicaffeoylquinic acid may interfere with the interaction between Nef and cell signaling molecules (such as PAK2) or proteins related to endocytosis mechanisms, thereby blocking Nef mediated endocytosis and degradation of MHC-I molecules from the cell surface. For Tat, it may competitively inhibit the binding of Tat to TAR RNA by binding to the alkaline region of Tat protein, or interfere with Tat's ability to recruit positive transcription elongation factor b (P-TEFb).

2. Molecular basis of anti-inflammatory and antioxidant effects

• Target: NF - κ B signaling pathway
• mechanism 1,4-Dicaffeoylquinic acid can inhibit the activity of I κ B kinase (IKK), prevent the phosphorylation and degradation of I κ B α, and thus retain NF - κ B dimer (p50/p65) in the cytoplasm, preventing it from entering the nucleus to initiate the transcription of pro-inflammatory genes. This directly leads to downregulation of the expression of inflammatory mediators such as TNF - α, IL-6, COX-2, and iNOS.
• Target: Keap1-Nrf2-ARE pathway
• mechanism As an electrophilic molecule, 1,4-dicaffeoylquinic acid (or its oxidized product) can modify cysteine residues on Keap1 protein, causing Nrf2 to dissociate and stabilize from Keap1. Nrf2 then enters the nucleus and binds to antioxidant response elements (ARE), initiating gene expression of a series of antioxidant enzymes (such as HO-1, NQO1, SOD, CAT), thereby enhancing the cell's antioxidant defense ability.

Evaluation of drug properties and pharmacokinetics

To promote 1,4-dicaffeoylquinic acid from a natural active ingredient to clinical use, it is necessary to rigorously evaluate its drug like and pharmacokinetic (ADME) properties.

Drugability assessment

According to Lipinski's "Rule of Five" and other classic pharmacological criteria, the behavior of 1,4-dicaffeoylquinic acid is as follows:
- molecular weight：516.4550 Da， Slightly above the threshold of 500 Da.
- LogP 1.1817, far less than 5, moderate lipophilicity.
- hydrogen bond donor The molecule contains multiple phenolic hydroxyl and carboxyl groups, and the number of hydrogen bond donors (>5) exceeds the rule limit.
- Hydrogen bond acceptor The same quantity (>10) exceeds the rule limit.

Therefore, 1,4-dicaffeoylquinic acid violates the Lipinski rule, especially in terms of high molecular weight and excessive hydrogen bond donors/acceptors. This usually indicates that its oral bioavailability may be low. However, there are many successful drugs outside of these "rules" in natural products. Other important pharmacological parameters include:
- TPSA 211.28 Å ², much higher than the threshold of 140 Å ², indicates poor transmembrane permeability, especially difficulty in penetrating the blood-brain barrier.
- Water solubility：0.5847 mg/mL， Belongs to moderate to low water solubility.
- HERG inhibition A prediction of 'no' indicates a low risk of cardiac toxicity.
- Ames test The predicted value is 0.0, indicating a low risk of mutagenicity.

Overall, 1,4-dicaffeoylquinic acid has a certain pharmacological basis (low toxicity, no hERG inhibition), but it faces significant challenges in oral absorption and bioavailability.

Pharmacokinetic characteristics

At present, direct research on the pharmacokinetics of 1,4-dicaffeoylquinic acid in vivo is relatively limited, but based on the study of its structural analogues (such as chlorogenic acid and 3,5-dicaffeoylquinic acid), its general characteristics can be inferred:

1. Absorption Poor oral absorption. Due to its large molecular weight and high polarity, it is difficult to passively diffuse through intestinal epithelial cells. It may mainly rely on intestinal transporters (such as monocarboxylate transporters MCTs) for absorption, but the efficiency is not high. Most oral 1,4-dicaffeoylquinic acid enters the colon directly.
2. Distribution Due to its high polarity and high binding rate with plasma proteins (especially albumin), its distribution volume may be small, mainly limited to plasma and extracellular fluid. Low blood-brain barrier permeability makes it difficult for it to enter the central nervous system.
3. Metabolism This is a crucial step in its internal disposal.
   • Intestinal metabolism In the intestine, it may be hydrolyzed by esterases, releasing caffeic acid and quinic acid. Caffeic acid can be further metabolized by gut microbiota into simple phenolic acids such as phenylpropanoic acid and phenylacetic acid.
   • Liver metabolism The part absorbed into the body mainly undergoes phase II metabolism in the liver, such as binding with glucuronic acid, sulfuric acid, or methyl, forming more water-soluble complexes for easier excretion.
   • Metabolism of gut microbiota The unabsorbed portion enters the colon and is widely metabolized by the gut microbiota, producing various low molecular weight phenolic acid metabolites that may have unique biological activities.
4. Excretion Mainly excreted in the form of metabolites through urine and bile. The excretion of prototype drugs may be very low.

key challenges The extremely low oral bioavailability is the biggest bottleneck limiting the clinical application of 1,4-dicaffeoylquinic acid. Its pharmacological activity may depend more on its local effects in the intestine (such as regulating gut microbiota, antioxidant) or mediated by its active metabolites produced in the body.

Clinical application prospects and prospects

Despite facing severe challenges in pharmacokinetics, the unique pharmacological activity spectrum of 1,4-dicaffeoylquinic acid, especially its multi-target anti HIV mechanism, still opens up promising prospects for its clinical application.

Potential application areas

1. Anti HIV therapy This is the most core application direction.
   • As an HIV entry inhibitor Given its ability to simultaneously target gp120 and CCR5/CXCR4, 1,4-dicaffeoylquinic acid or its derivatives have the potential to be developed as novel HIV entry inhibitors, particularly as prophylactic microbicides for vaginal or rectal administration to block sexual transmission of HIV. This local administration method can avoid the problem of low oral bioavailability.
   • As a component of multi-target combination therapy It inhibits the activity of integrase, Nef, and Tat, allowing it to be used in combination with existing reverse transcriptase inhibitors, protease inhibitors, etc., forming a multi-target, multi link combination therapy, which is expected to reduce the development of drug resistance and potentially clear latent virus pools.
2. Anti inflammatory and antioxidant related diseases: Its powerful anti-inflammatory and antioxidant activities can be used to explore its application in chronic inflammatory diseases (such as inflammatory bowel disease, arthritis), metabolic diseases (such as non-alcoholic fatty liver disease, diabetes complications) and neurodegenerative diseases (such as Alzheimer's disease, although its BBB permeability is low, it can play a role through active metabolites or nano delivery systems).
3. As a lead compound The chemical structure of 1,4-dicaffeoylquinic acid provides a good modification platform for medicinal chemists. By structurally modifying the phenolic hydroxyl, carboxyl, or double bonds in its molecules, the aim is to:
   • Improve metabolic stability Replace easily hydrolyzed ester bonds with amide or ether bonds.
   • Improve oral bioavailability As designed in the prodrug, the polar groups are temporarily shielded to improve membrane permeability.
   • Enhance target selectivity Optimize its binding ability to specific targets (such as CCR5 vs. CXCR4, or integrase) through structure-activity relationship (SAR) studies.

Challenges faced and future research directions

1. Pharmacokinetic optimization How to overcome its low oral bioavailability is the primary issue. Future research should focus on:
   • New drug delivery system Such as liposomes, nanoparticles, phospholipid complexes, etc., to enhance their oral absorption or achieve targeted delivery.
   • Structural modification As mentioned earlier, design more stable and easily absorbable derivatives or prodrugs through medicinal chemical methods.
2. In vivo efficacy verification Currently, the vast majority of activity data comes from in vitro experiments. It is necessary to establish appropriate animal models (such as humanized mouse models of HIV infection, inflammatory bowel disease models, etc.) to systematically evaluate their in vivo efficacy, pharmacokinetics, and toxicity.
3. In depth elucidation of structure-activity relationship (SAR)A series of 1,4-dicaffeoylquinic acid analogues need to be synthesized systematically, combined with molecular docking, molecular dynamics simulation, and biological activity testing to accurately analyze the key structural elements that bind to different targets (CCR5, integrase, Nef, etc.), providing guidance for rational drug design.
4. Comprehensive analysis of the mechanism of action The inhibitory mechanism of Nef and Tat is not fully understood, and further molecular and cellular biology research is needed. In addition, whether its in vivo activity mainly depends on its metabolites also needs to be elucidated through metabolomics and pharmacokinetic pharmacodynamic (PK-PD) correlation studies.

Conclusion

1,4-Dicaffeoylquinic acid, a phenolic acid compound originating from nature, demonstrates the eternal value of natural products in drug discovery with its unique chemical structure and multi-target biological activity, especially its enormous potential in the field of anti HIV. It provides new ideas for addressing the global challenge of HIV infection by simultaneously acting on multiple links such as virus entry, integration, and regulation, as well as its impact on host immune regulation.

However, the journey from "natural active ingredients" to "clinical drugs" is still long and challenging. The inherent physical and chemical property defects, especially low oral bioavailability, are the core bottleneck restricting its development. Future research must closely integrate modern medicinal chemistry, pharmacy, and in-depth molecular pharmacology research. On the one hand, innovative structural modification and delivery technologies should be used to "leverage strengths and avoid weaknesses", and on the other hand, comprehensive in vivo action networks and active metabolites should be revealed through systems biology methods.

The study of 1,4-dicaffeoylquinic acid is not only an exploration of a specific compound, but also a practice of the paradigm of natural product drug development. It reminds us that in addition to pursuing the modern drug design concept of "single target, high affinity", natural products that originate from natural evolution and have the characteristics of "multi-target, weak interaction" still contain enormous wisdom for treating complex diseases. We have reason to believe that, with the continuous deepening of research and the progress of technical means, 1,4-dicaffeoylquinic acid and its derivatives will eventually find their own place in the fight against diseases, especially AIDS.