What is Caffeic Acid:
Synonyms: 3,4-Dihydroxycinnamic acid; 2-Propenoic acid, 3-(3,4-dihydroxyphenyl); 3,4-Dihydroxybenzeneacrylic acid;3-(3,4-Dihydroxyphenyl)-2-propenoic acid;4-(2',Carboxyvinyl)-1,2-dihydroxybenzene
Molecular formula: C9H8O4
Molecular weight: 180.16
CAS No.: 331-39-5
Melt Point: 194-198°C
Solubility: Soluble in water. (> 0.65 ug/ml at 25.0 C)
Caffeic acid and its derivative caffeic acid phenethyl ester (CAPE) are produced in many plants including: pears, basil, thyme, verbena, tarragon, oregano, wood betony, burning bush, turmeric, dandelion, yarrow, horsetail, rosemary, hawthorn and coffee.
The amount of caffeic acid is strongly dependent on the plant species.
Both caffeic acid and chlorogenic acid have been shown to be absorbed in humans. Caffeic acid absorption is hampered when it is esterified with quinic acid to form chlorogenic acid.
In laboratory experiments, colonies of a nut tree mould were grown on extracts of walnut and pistachio. Next, fungal colonies were exposed to three compounds thought to be antioxidants: gallic acid, which has aflatoxin-combating impacts in walnuts, and chlorogenic acid and caffeic acid.
Caffeic acid outperformed the other antioxidants, reducing aflatoxin production by more than 95 percent. The studies are the first to show that oxidative stress that would otherwise trigger or enhance Aspergillus flavus aflatoxin production can be stymied by caffeic acid.
This opens the door to using natural anti-fungicide methods by supplementing trees with antioxidants.
Oral administration of high doses of caffeic acid in rats has caused stomach papillomas, leading to the perception of caffeic acid as carcinogenic. In the same study, only high doses of combined antioxidants, including caffeic acid, showed a significant decrease in growth of colon tumors in those same rats. No significant effect was noted otherwise.
Caffeic Acid is still listed under older Hazard Data sheets  as a potential carcinogen because of two early experiments on rats and mice.
More recent data show that bacteria in the rats' guts may alter the formation of metabolites of Caffeic Acid. There have been no known ill-effects of Caffeic Acid in humans.
Caffeic Acid and its derivative, Caffeic Acid Phenethyl Ester (CAPE) have shown tumor-shrinking properties. When an anti-cancer drug was being sought, Caffeic Acid and CAPE were derived from Burning Bush (Euonymus alatus). "The subcutaneous and oral administrations of CA and CAPE significantly reduced liver metastasis. These results confirm the therapeutic potential of the compounds and suggest that the anti-metastatic and anti-tumor effects of CA and CAPE are mediated through the selective suppression of MMP-9 enzyme activity and transcriptional down-regulation by the dual inhibition of NF-B as well as MMP-9 catalytic activity."
A study using the caffeic acid phenethyl ester (CAPE) showed a positive effect on reducing carcinogenic incidence. Caffeic acid phenethyl ester (CAPE) is an active component of propolis from honeybee hives.it is known to have antimitogenic, anticarcinogenic, anti-inflammatory, and immunomodulatory properties.
Another study also showed that CAPE suppresses acute immune and inflammatory responses and holds promise for therapeutic uses to reduce inflammation.
This anti-inflammatory and anti-cancer property has also been shown to protect skin cells when exposed to ultraviolet (UV) radiation, in particular UVC radiation and UVB radiation. This anti-cancer effect was also seen when mice skin was treated with bee propolis and exposed to TPA (a chemical) that induced skin papillomas. CAPE significantly reduced the number of papillomas.
Caffeic Acid and chlorogenic acid from coffee beans both reduced DNA methylation in vitro in two lines of human cancer cells. DNA methylation contributes to the growth of tumors and regulates the epigenetics of cells that are passed along with DNA to future generations .
- M Hirose, Y Takesada, H Tanaka, S Tamano, T Kato and T Shirai (1998). "Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4- methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi- organ carcinogenesis model". Carcinogenesis 19: 207-212.
- Journal of Nutrition. Chlorogenic acid and caffeic acid are absorbed in humans. Jan. Margreet R. Olthof, P.C.H. Hollman, and M.B. Katan. Journal of Nutrition. 2001; 131:66-71.
- PubMed: Rats. Carcinogenicity of antioxidants BHA, caffeic acid, sesamol, 4- methoxyphenol and catechol at low doses, either alone or in combination, and modulation of their effects in a rat medium-term multi- organ carcinogenesis model. M Hirose, Y Takesada, H Tanaka, S Tamano, T Kato and T Shirai. Carcinogenesis. 1998; 19:207-212..
- FASEB Journal: Therapeutic Effects. Novel and therapeutic effect of caffeic acid and caffeic acid phenyl ester on hepatocarcinoma cells: complete regression of hepatoma growth and metastasis by dual mechanism. TAE-WOOK CHUNG, SUNG-KWON MOON, YOUNG-CHAE CHANG, JEONG-HEON KO, YOUNG-CHOON LEE, GUN CHO, SOO-HYUN KIM, JONG-GUK KIM and CHEORL-HO KIM. The FASEB Journal. 2004; 18:1670-681.
- PubMed: Cancer Inhibitor. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa. K Natarajan, S. Singh, T.R. Burke Jr, D. Grunberger, and B.B. Aggarwal. Proc Natl Acad Sci USA. 1996 August 20; 93(17): 9090–9095.
- Karger Online: Inflammation. Caffeic Acid Phenethyl Ester Induces Leukocyte Apoptosis, Modulates Nuclear Factor-Kappa B and Suppresses Acute Inflammation. 2000. Zsolt Orbana, N. Mitsiadesb, T.R. Burke Jr., M. Tsokosb, and G.P. Chrousosa. NeuroImmunoModulation. 2000; 7:99-105.
- Folia Biologica: Skin. UVC-Protective Effect of Caffeic Acid on Normal and Transformed Human Skin Cells in Vitro.J. NERADIL, R. VESELSK, J. SLANINA. Folia Biologica (Praha). 2003; 49:197-202.
- Carcinogenesis: UVB. Caffeic acid suppresses UVB radiation-induced expression of interleukin-10 and activation of mitogen-activated protein kinases in mouse. Vanisree Staniforth, Lu-Tang Chiu and Ning-Sun Yang. Carcinogenesis. 2006; 27(9):1803-1811..
- Carcinogenesis: Mice Skin. Inhibitory effects of caffeic acid phenethyl ester (CAPE) on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mouse skin and the synthesis of DNA, RNA and protein in HeLa cells. Mou-Tuan Huang, Wei Ma, Patricia Yen, Jian-Guo Xie, Jingkang Han, Krystyna Frenkel, Dezider Grunberger and Allan H. Conney. 1996; 17(4):761-765..
- PubMed: Mice Skin. Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate. Huang MT, Smart RC, Wong CQ, Conney AH. Cancer Research. 1988 Nov 1;48(21):5941-6.
- Agricultural Research: Nuts. "Nuts’ New Aflatoxin Fighter: Caffeic Acid?" Bruce C. Campbell and Jong H. Kim. USDA-ARS Western Regional Research Center. Agricultural Research. Oct 2006..
- PubMed: DNA Methylation. Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. Lee WJ, Zhu BT. Carcinogenesis. 2006 Feb;27(2):269-77. Epub 2005 Aug 4.
- Hydroxylated aromatic inhibitors of HIV-1 integrase: T.R. Burke Jr., et al.; J. Med. Chem. 38, 4171 (1995) Abstract
- Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B: K. Natarajan, et al.; PNAS 93, 9090 (1996)
- Apoptosis and altered redox state induced by caffeic acid phenethyl ester (CAPE) in transformed rat fibroblast cells: C. Chiao, et al.; Cancer Res. 55, 3576 (1995)
- Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in a rat model of inflammation: P. Michaluart, et al.; Cancer Res. 59, 2347 (1999) Abstract
- Caffeic acid phenethyl ester induces leukocyte apoptosis, modulates nuclear factor-kappa B and suppresses acute inflammation: Z. Orban, et al.; Neuroimmunomodulation 7, 99 (2000) Abstract
- Caffeic acid phenethyl ester inhibits T-cell activation by targeting both nuclear factor of activated T-cells and NF-kappaB transcription factors: N. Marquez, et al.; J. Pharmacol. Exp. Ther. 308, 993 (2004) Abstract
- Caffeic acid derivatives: in vitro and in vivo anti-inflammatory properties: F.M. da Cunha, et al.; Free Radic. Res. 38, 1241 (2004) Abstract
Write by Peter Lau, Edited by Nuttakarn