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Chemical Structure| 331-39-5 Chemical Structure| 331-39-5

Structure of Caffeic Acid
CAS No.: 331-39-5

Chemical Structure| 331-39-5

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Caffeic acid is a hydroxycinnamic acid, a naturally occurring organic compound isolated and purified from the herb of Boehmeria siamensis Craib., with antioxidant, antineoplastic, anti-HIV, choleretic, hepatotropic, and is a strong inhibitor of neutrophil elastase.

Synonyms: 3,4-Dihydroxycinnamic Acid

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Product Citations

Product Citations

Scott, Jared Lee ;

Abstract: Breast cancer (BC) is the second greatest contributor to the death of women, second only to heart disease, and is the most common type of cancer. BC treatments involve the administration of adjuvant chemotherapies which often have side effects that prevent patients from completing the full course of drugs or the refusal to take these potentially lifesaving treatments. Many chemotherapy drugs are developed from plants, and some plant extracts can exhibit significant anticancer activities while also having less toxic side effects. However, these potential "plant therapeutics" suffer from poor oral bioavailability. The Apiaceae plant family consists of several species that are used as culinarily spices including anise, celery, cumin, and coriander, all of which have demonstrated antioxidant, chemopreventive, and anticancer activities. One method to improve the systemic distribution of anticancer phytochemicals is their encapsulation in naturally produced membrane bound nanoparticles known as exosomes. Exosomes are produced by most eukaryotic organisms, as well as some prokaryotes, and are involved in cell-to-cell communication through the delivery of proteins, nucleic acids, and small molecules from one cell to another. Exosomes are found in many extracellular fluids including blood, urine, and milk. Bovine milk exosomes represent a scalable source of exosomes that are already present in the human diet and have been explored as a drug delivery system that can increase effectiveness and improve bioavailability. To enhance the loading potential and anticancer bioactivity of Apiaceae phytochemicals, an acid hydrolysis (AH) of the glycoside compounds present in ethanolic spice extracts was performed on eight ethanolic spice extracts. The antiproliferative effects of AH extracts and exosomal formulations were assayed with three model types of BC cells. Cumin was characterized in greater detail as these extracts had the highest concentration of terpenoids and alkaloids while also having significant concentrations of phenolics and responded well to AH with increased antiproliferative activity and exosomal loading. Extracts and exosomal formulations exhibited broad antiproliferative effects with lower IC50s in the extracts delivered with exosomes. The phytochemical contents of AH-cumin extracts and exosomal formulations were assayed with HPLC-DAD, LC-MS/MS, and GC-MS, while the potential anticancer mechanisms of these treatments were investigated in triple negative BC (TNBC). AHcumin extracts were determined to have numerous phenolic compounds, many of which have known anticancer mechanisms, in addition to several alkaloids and lipid compounds, some of which have activities that could contribute to the anticancer effects observed. Mechanistically, AH-cumin extracts and exosomal formulations were shown to interact with multidrug resistance proteins and inhibit lipid metabolism in TNBC cells. These results indicate that acid hydrolyzed cumin extracts delivered through exosome nanoparticles represent a possible avenue towards the development of novel treatments for TNBC, the hardest type of BC to treat.

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Product Details of Caffeic Acid

CAS No. :331-39-5
Formula : C9H8O4
M.W : 180.16
SMILES Code : O=C(O)/C=C/C1=CC=C(O)C(O)=C1
Synonyms :
3,4-Dihydroxycinnamic Acid
MDL No. :MFCD00004392
InChI Key :QAIPRVGONGVQAS-DUXPYHPUSA-N
Pubchem ID :689043

Safety of Caffeic Acid

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335-H351-H361
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Description
Caffeic acid is an inhibitor of both TRPV1 ion channel and 5-Lipoxygenase (5-LO).

In Vitro:

Cell Line
Concentration Treated Time Description References
Bovine mammary epithelial cells 125 or 250 mg/ml 12 hours CA pretreatment inhibited E. coli B1-induced inflammatory responses and oxidative stress, and restored lipid homeostasis. Front Immunol. 2022 Oct 20;13:1005430.
HTB-34 human cervical cancer cells 100 µM 24 hours Caffeic acid activates AMPK, inhibits cell proliferation, and promotes apoptosis Int J Mol Sci. 2017 Feb 21;18(2):462.
Colon myofibroblasts CCD-18Co 50 µM, 10 µM, 1 µM 24 hours Investigated the effects of caffeic acid on COX-2 expression, PGE2 biosynthesis, and inflammatory cytokines/chemokines (IL-8, MCP-1, IL-6) in IL-1β-stimulated colon myofibroblasts. Results: Caffeic acid dose-dependently reduced PGE2 levels (significant at 50 and 10 μM), downregulated COX-2 expression (significant at 50 and 10 μM), and only at 50 μM significantly decreased IL-8 secretion (~27%), with no effect on MCP-1 or IL-6. Nutrients. 2021 Feb 8;13(2):554.
Primary bovine mammary epithelial cells 10, 25, 50 μg/mL 3 hours pretreatment followed by LPS stimulation for 12 hours Caffeic acid protected cells from LPS-induced structural damage and apoptosis by inhibiting NF-κB and MAPK activation and reducing proinflammatory cytokine expression Mediators Inflamm. 2019 Apr 30;2019:1897820.
Primary bovine mammary epithelial cells 10, 25, 50 μg/mL 3 hours pretreatment followed by LPS stimulation for 12 hours Caffeic acid attenuated LPS-induced structural damage and apoptosis by inhibiting NF-κB and MAPK activation, and reduced proinflammatory cytokine release Mediators Inflamm. 2019 Apr 30;2019:1897820.
BCPAP cells 16 µg/mL 48 hours Inhibited BCPAP cell proliferation with an inhibition rate of ~79% J Nanobiotechnology. 2024 Sep 18;22(1):571.
Rat cortical slices 100 µM CA prevented induced loss of reductive capacity, cell damage, and oxidative damage. Int J Mol Sci. 2023 May 24;24(11):9218.
HEK-Gα15/ETA and HEK-Gα15/ETB cells 30, 25, 20, 15, 10, 5 and 0 µM To test the antagonistic activity of the compounds on ETA and ETB receptors. Results showed that these twin drugs could not antagonize ETA and ETB receptors. Drug Des Devel Ther. 2020 Mar 5;14:977-992.
HEK-Gα15/AT1 cells 30, 25, 20, 15, 10, 5 and 0 µM To test the antagonistic activity of compound 1a on Ang II-AT1 receptor, with an IC50 of 340nM. Drug Des Devel Ther. 2020 Mar 5;14:977-992.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Drosophila melanogaster Dextran sulfate sodium (DSS)-induced ulcerative colitis model Oral 0.5 mM and 1 mM Daily administration for 7 days CA significantly improved the survival rate of UC flies, restored their motility and digestive abilities, protected intestinal morphology and homeostasis, and reduced intestinal cell damage. Additionally, CA alleviated intestinal damage by inhibiting apoptosis mediated by mitochondrial damage and reducing immune overactivation in the intestine. Drug Des Devel Ther. 2025 Mar 22;19:2157-2172
C57 mice S. aureus-induced endometritis model Intraperitoneal injection 10, 20, 30 mg/kg Uterine tissues were harvested 24 hours later CA significantly alleviated S. aureus-induced uterine injury, MPO activity, the contents of inflammatory factors TNF-α and IL-1β, and NF-κB activation. Meanwhile, CA significantly inhibited S. aureus-induced ferroptosis, as confirmed by decreased MDA and iron concentration and up-regulated GPX4 expression and GSH level. Furthermore, CA attenuated S. aureus-induced HIF-1α and phosphorylated mTOR expression and increased phosphorylated AMPK expression. J Cell Mol Med. 2024 Oct;28(20):e70175
BALB/c nude mice Xenograft model Tail vein injection 2 mg/kg 5 times per week for 14 days Significantly inhibited the volume and weight of human papillary thyroid tumors J Nanobiotechnology. 2024 Sep 18;22(1):571.
Sprague-Dawley rats D-galactose-induced aging model Oral gavage 20 or 40 mg/kg Once daily for 8 weeks Caffeic acid alleviates memory and hippocampal neurogenesis deficits induced by D-galactose Nutrients. 2022 May 23;14(10):2169
ICR mice E. coli or K. pneumoniae infection model Oral 25 or 50 mg/kg/day Once daily for 10 days CA pretreatment improved the survival rate of mice and alleviated inflammatory responses and tissue damage in mammary glands. Front Immunol. 2022 Oct 20;13:1005430.
Rats Alzheimer’s disease model Oral 50 mg/kg Once daily for 25 days CA significantly counteracted the worsening of cognitive abilities and induced changes in levels of AChE, glutathione, catalase, lipid peroxidation, and superoxide dismutase. Int J Mol Sci. 2023 May 24;24(11):9218.
C57BL/6 mice LPS-induced sepsis model Intraperitoneal injection 50 mg/kg Single dose, LPS challenge 6 h later CA significantly improved the survival rate of septic mice, reduced serum IL-1β and TNF-α levels, and inhibited GSDMD activation in peritoneal macrophages MedComm (2020). 2023 Apr 20;4(3):e255.

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00065715 Common Cold Phase 3 Completed - United States, Wisconsin ... More >> University of Wisconsin-Madison Department of Family Medicine Madison, Wisconsin, United States, 53706-1490 Less <<
NCT02050334 Healthy Phase 1 Completed - United States, Indiana ... More >> IU Health Neuroscience Center Indianapolis, Indiana, United States, 46202 Less <<
NCT02050334 - Completed - -
NCT02744703 Matrix Metalloproteinase Inhib... More >>itors Composite Resins Less << Not Applicable Completed - -
NCT03049046 Amyotrophic Lateral Sclerosis Phase 1 Recruiting March 30, 2018 United States, Indiana ... More >> Indiana University, IU Health Physicians Neurology Recruiting Indianapolis, Indiana, United States, 46202 Contact: Sandra Guingrich, LPN, CCRC    317-963-7382    sguingri@iu.edu    Principal Investigator: Robert Pascuzzi, MD Less <<
NCT02351622 Immune Thrombocytopenia Phase 3 Completed - China, Shandong ... More >> Shandong University Qilu hospital Jinan, Shandong, China, 250012 Less <<
NCT03070262 Esophagus Cancer Phase 3 Enrolling by invitation December 2020 China, Henan ... More >> The Clinical Medical College, The First Affiliated Hospital of Henan University of Science and Technology Luoyang, Henan, China, 471003 Less <<
NCT02556814 Immune Thrombocytopenia Phase 4 Unknown September 2017 China, Shandong ... More >> Qilu Hospital, Shandong University Recruiting Jinan, Shandong, China Contact: Ming Hou, Dr.    +86-531-82169114 ext 9879    houming@medmail.com.cn    Principal Investigator: Ming Hou, Dr. Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

5.55mL

1.11mL

0.56mL

27.75mL

5.55mL

2.78mL

55.51mL

11.10mL

5.55mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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