In the search for pharmaceutically active compounds from natural products, it is crucial and challenging to develop separation or purification methods that target not only structurally similar compounds but also those with specific pharmaceutical functions. The adsorption-based method is widely employed in this field and holds potential for this application, given the diverse range of functional monomers that can be chosen based on structural or functional selectivity. In this work, an imidazolium ionic liquid (IL) modified paper membrane was synthesized via microwave reaction. Caffeic acid (CA), with potential interactions with imidazolium IL and a representative component of phenolic acids in Taraxaci Herba, was chosen as a target compound. After optimization of synthesis and extraction parameters, the resulting extraction membrane could be used to quantitatively analyze CA at ng/ml level, and to extract CA\'s analogues from the sample matrix. Cheminformatics confirmed the presence of structural and functional similarity among these extracted compounds. This study offers a novel approach to preparing a readily synthesized extraction membrane capable of isolating compounds with structural and functional analogies, as well as developing a membrane solid-phase extraction-based analytical method for natural products.

Lifestyle influences physical and cognitive development during the period of adolescence greatly. The most important of these lifestyle factors are diet and stress. Therefore, the aim of this study was to investigate the impact of high fat diet (HFD) and chronic mild stress on cognitive function and anxiety-like behaviors in young rats and to study the role of caffeic acid as a potential treatment for anxiety and cognitive dysfunction. Forty rats were assigned into 4 groups: control, HFD, HFD + stress, and caffeic acid-treated group. Rats were sacrificed after neurobehavioral testing. We detected memory impairment and anxiety-like behavior in rats which were more exaggerated in stressed rats. Alongside the behavioral changes, there were biochemical and histological changes. HFD and/or stress decreased hippocampal brain-derived neurotrophic factor (BDNF) levels and induced oxidative and inflammatory changes in the hippocampus. In addition, they suppressed Wnt/β-catenin pathway which was associated with activation of glycogen synthase kinase 3β (GSK3β). HFD and stress increased arginase 1 and inducible nitric oxide synthase (iNOS) levels as well. These disturbances were found to be aggravated in stressed rats than HFD group. However, caffeic acid was able to reverse these deteriorations leading to memory improvement and ameliorating anxiety-like behavior. So, the current study highlights an important neuroprotective role for caffeic acid that may guard against induction of cognitive dysfunction and anxiety disorders in adolescents who are exposed to HFD and/or stress.

Eleven compounds including caffeic acid (CA), 4 kinds of caffeoylquinic acid (CQA) and 6 kinds of dicaffeoylquinic acid (DCQA), were selected to evaluate the anti-inflammatory effectiveness using mouse primary peritoneal macrophages in the absence or presence of lipopolysaccharide (LPS). The optimal non-cytotoxic doses of each individual compound were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Pro-inflammatory (TNF-α, IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines secreted by treated macrophages were analyzed using the enzyme-linked immunosorbent assay. Cytokine secretion profiles of each individual test sample at optimal non-cytotoxic doses were further analyzed using Principal Component Analysis (PCA). The results showed that CA and all selected CQAs exhibited lower cytotoxicity (IC50: >50 μmol/l). Both CA and 5-CQA were found to have the most significant contributions for inhibiting pro-inflammatory cytokines, but increasing anti-inflammatory cytokine secretions, evidencing that CA at 10 μmol/l and 5-CQA at 25 μmol/l can be qualified as potent anti-inflammatory agents for treating inflammation-related diseases.

A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, aiming to design anticancer and antimicrobial drugs, respectively. Among all the synthesized derivatives, compound CTh7 demonstrated the highest potency as a DHFR inhibitor, with an IC50 value of 0.15 μM. Additionally, it exhibited significant cytotoxic properties, with an IC50 value of 8.53 µM. The molecular docking analysis of the CTh7 compound revealed that it forms strong interactions with key residues of homo sapiens DHFR such as Glu30, Phe34, Tyr121, Ile16, Val115, and Phe31 within the target protein binding site and displayed excellent docking scores and binding energy (-9.9; -70.38 kcal/mol). Additionally, synthesized compounds were screened for antimicrobial properties, revealing significant antimicrobial potential against bacterial strains and moderate effects against fungal strains. Specifically, compound CTh3 exhibited notable antibacterial efficacy against Staphylococcus aureus (MIC = 5 µM). Similarly, compound CTh4 demonstrated significant antibacterial activity against both Escherichia coli and Pseudomonas aeruginosa, with MIC values of 5 µM for each. A docking analysis of the most active antimicrobial compound CTh3 revealed that it forms hydrogen bonds with Thr121 and Asn18, a π-cation bond with Phe92, and a salt bridge with the polar residue Asp27.

Chlorogenic acid (CHA) is a phenolic substance found in various edible plants, such as tea and green coffee extracts. This chemical has demonstrated significant efficacy in reducing the probability of many diseases in preclinical and clinical environments. Chlorogenic acid (CHA) possesses several pharmacological attributes, such as anticancer, hepatoprotective, antimicrobial, immune-suppressant, antioxidant, and antidiabetic activities. Its applications extend to multiple industries, such as food, chemicals, medicine, and healthcare. Studies have shown that CHA can exert its anticancer effects through numerous mechanisms. It can hinder the process of cell division, trigger cell apoptosis, and suppress an increase in cancerous cell growth. The literature research conducted for this study revealed a variety of molecular and cellular processes influencing distinct signaling pathways. These mechanisms include angiogenesis, invasion and migration, oxidative stress, inflammation, cell cycle arrest, and proliferation.However, significant issues surround the use of CHA, primarily due to its limited bioavailability in animal models. This review focuses on the chemistry, natural sources, pharmacokinetics, and underlying mechanisms of action of CHA and its clinical utility in treating life-threatening diseases, such as cancer. The manuscript provides insight into novel formulation approaches.

Myocardial fibrosis is a pathological, physiological change that results from alterations, such as inflammation and metabolic dysfunction, after myocardial infarction (MI). Excessive fibrosis can cause cardiac dysfunction, ventricular remodeling, and heart failure. Caffeic acid (CA), a natural polyphenolic acid in various foods, has cardioprotective effects. This study aimed to explore whether CA exerts a cardioprotective effect to inhibit myocardial fibrosis post-MI and elucidate the underlying mechanisms. Histological observations indicated that CA ameliorated ventricular remodeling induced by left anterior descending coronary artery ligation in MI mice and partially restored cardiac function. CA selectively targeted transforming growth factor-β receptor 1 (TGFBR1) and inhibited TGFBR1-Smad2/3 signaling, reducing collagen deposition in the infarcted area of MI mice hearts. Furthermore, cell counting (CCK-8) assay, 5-ethynyl-2\'-deoxyuridine assay, and western blotting revealed that CA dose-dependently decreased the proliferation, collagen synthesis, and activation of the TGFBR1-Smad2/3 pathway in primary cardiac fibroblasts (CFs) stimulated by TGF-β1 in vitro. Notably, TGFBR1 overexpression in CFs partially counteracted the inhibitory effects of CA. These findings suggest that CA effectively mitigates myocardial fibrosis and enhances cardiac function following MI and that this effect may be associated with the direct targeting of TGFBR1 by CA.

BACKGROUND: Dandelion contains hundreds of active compounds capable of inhibiting urease activity, but the individual compounds have not yet been fully identified, and their effects and underlying mechanisms are not clear. The present study aimed to screen the urease inhibition active compounds of dandelion by urease inhibitory activity evaluation HPLC-tandem mass spectrometry analysis, their mechanism of urease inhibition by polyphenols was explored using enzyme kinetic studies via Lineweaver-Burk plots. Other investigations included isothermal titration calorimetry and surface plasmon resonance sensing, fluorescence quenching experiments, and single ligand molecular docking and two-ligand simultaneous docking techniques.
RESULTS: The results indicated that the ethyl acetate fraction of dandelion flower exhibited the greatest inhibition (lowest IC50 0.184 ± 0.007 mg mL-1). Chlorogenic acid, caffeic acid and luteolin could be effective urease inhibitors that acted in a non-competitive inhibition manner. Individually, chlorogenic acid could not only fast bind to urease, but also dissociate rapidly, whereas luteolin might interact with urease with the weakest affinity. The chlorogenic acid-caffeic acid combination exhibited an additive effect in urease inhibition. However, the chlorogenic acid-luteolin and caffeic acid-luteolin combinations exhibited antagonistic effects, with the caffeic acid-luteolin combination showing greater antagonism.
CONCLUSIONS: The present study reveals that chlorogenic acid, caffeic acid and luteolin are major bioactive compounds for urease inhibition, indicating the molecular mechanisms. The antagonistic effects were observed between luteolin and chlorogenic acid/caffeic acid, and the interactions of the catalytic site and flap may account for the antagonistic effects. © 2024 Society of Chemical Industry.

Caffeic acid, a phenolic compound of the hydroxycinnamic acid family, is abundant in various plant-based foods, such as fruits, vegetables, and coffee, alongside other biologically active compounds. Recognizing its potential to address various health issues and its widespread presence in commonly consumed foods underscores the importance of comprehending and harnessing the benefits of caffeic acid for human nutrition and well-being. This versatile substance, characterized by acrylic and phenolic functional groups, plays a pivotal role in the food and pharmaceutical industries. Furthermore, a detailed exploration of its pharmacokinetic properties, absorption, distribution, metabolism, and excretion enhances our understanding of how the human body processes it. Functioning as a precursor for essential compounds, caffeic acid contributes to formulations with notable anti-inflammatory, antiviral, anti-cancer, anti-diabetic, antibacterial, neuroprotective, and hepatoprotective qualities. Its current applications in treating Parkinson\'s and Alzheimer\'s disease underscore its therapeutic significance. This comprehensive analysis sheds light on caffeic acid\'s importance, showcasing its diverse applications across various domains and paving the way for further research and development to fully unlock its therapeutic potential. In conclusion, caffeic acid emerges as a bioactive substance with a broad spectrum of pharmacological properties, suggesting its potential utility in diverse therapeutic contexts. The comprehensive information provided in this article serves as a foundation for further research and learning regarding the various ways that caffeic acid supports human health.

OBJECTIVE: Apoptosis resistance in cancer cells adapted to acidic microenvironments poses a challenge for effective treatment. This study investigated the potential use of caffeic acid as an adjunct therapy to overcome drug resistance in colorectal cancer cells under acidic conditions.
METHODS: Long-term exposure to low-pH conditions induced resistance in HCT116 colorectal cancer cells. The effects of caffeic acid on proliferation, clonogenicity, and apoptosis induction were assessed alone and in combination with oxaliplatin and 5-Fluorouracil. The signaling pathways involved in drug resistance were examined by assessing the activities of PI3K/Akt and ERK1/2.
RESULTS: Caffeic acid inhibited the proliferation and clonogenicity of acid-adapted cancer cells, and enhanced apoptosis when combined with anticancer drugs. Mechanistically, caffeic acid attenuated the hyperactivation of the PI3K/Akt and ERK1/2 signaling pathways associated with drug resistance.
CONCLUSIONS: Caffeic acid is a promising therapeutic agent for targeting resistant cancer cells in acidic microenvironments. Its ability to inhibit proliferation, sensitize cells to apoptosis, and modulate signaling pathways highlights its potential for overcoming drug resistance in cancer therapy.

Resveratrol and caffeic acid are some of the most consumed antioxidants during the day, so their importance as sources and their benefits need to be evaluated and updated. This survey aimed not only to analyze whether young Romanian consumers are informed about the benefits of antioxidants in general, and resveratrol and caffeic acid in particular, but also to observe the degree of nutritional education of these participants. Young consumers know the concept of antioxidants relatively well; they managed to give examples of antioxidants and indicate their effects. The majority of those chosen drink wine and coffee, but many are unaware of their health advantages and antioxidant properties. Students are less familiar with the antioxidant chemicals resveratrol and caffeic acid. It is advised to have a thorough understanding of these significant antioxidants and their nutritional content as they are present in our regular diets, and further studies on different kinds of antioxidants are required to increase the awareness of people concerning their importance in daily life.