Caffeic acid

Caffeic acid
IUPAC name

3-(3,4-Dihydroxyphenyl 2-propenoic acid
3,4-Dihydroxy-cinnamic acid
trans-Caffeate
3,4-Dihydroxy-trans-cinnamate)
(E)-3-(3,4-dihydroxyphenyl)-2-propenoic acid
3,4-Dihydroxybenzeneacrylicacid
3-(3,4-Dihydroxyphenyl)-2-propenoic acid
Identifiers
CAS number 331-39-5 Y
PubChem 689043
ChemSpider 600426 Y
UNII U2S3A33KVM Y
DrugBank DB01880
KEGG C01481 Y
ChEBI CHEBI:16433 Y
ChEMBL CHEMBL145 Y
Jmol-3D images Image 1
Properties
Molecular formula C9H8O4
Molar mass 180.16 g/mol
Exact mass 180.042259
Density 1.478 g/cm³
Melting point

223–225 °C
λmax 327 nm and a shoulder at c. 295 nm in acidified methanol[1]
Related compounds
Related compounds Chlorogenic acid
Cichoric acid
Coumaric acid
Quinic acid
 Y (verify) (what is: Y/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Caffeic acid is a hydroxycinnamic acid, a naturally occurring organic compound. This yellow solid consists of both phenolic and acrylic functional groups. It is found in all plants because it is a key intermediate in the biosynthesis of lignin, one of the principal sources of biomass.

Contents

Occurrence and biological function

Caffeic acid, which is unrelated to caffeine, is biosynthesized by hydroxylation of coumaroyl ester of quinic ester. This hydroxylation produces the caffeic acid ester of shikimic acid, which converts to chlorogenic acid. It is the precursor to ferulic acid, coniferyl alcohol, and sinapyl alcohol, all of which are significant building blocks in lignin.[2] The transformation to ferulic acid is catalyzed by the enzyme caffeic acid-O-methyltransferase.

Caffeic acid and its derivative caffeic acid phenethyl ester (also known as CAPE, molecular formula : C17H16O4,molar mass :284.30654 g/mol, exact mass : 284.104859) are produced in many kinds of plants.[3][4][5]

In traditional and alternative medicine

Caffeic acid has been shown to inhibit carcinogenesis, although other experiments show possible carcinogenic effects. It is also known as an antioxidant in vitro and also in vivo.[5] Caffeic acid also shows immunomodulatory and antiinflammtory activity.

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.[6]

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.[7]

Caffeic acid is still listed under older Hazard Data sheets[8] 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.[9][10] 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-κB as well as MMP-9 catalytic activity." [11] 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.[12] It is known to have antimitogenic, anticarcinogenic, anti-inflammatory, and immunomodulatory properties.[13]

Another study also showed that CAPE suppresses acute immune and inflammatory responses and holds promise for therapeutic uses to reduce inflammation.[14]

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[15] and UVB radiation.[16] 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.[17][18] 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.[19]

Caffeic acid has been shown to be an inhibitor of the lipoxygenase enzyme that forms leukotrienes from arachidonic acid. This function has been useful in scientific experiments to elucidate the roles of the leukotrienes in various inflammatory responses.[20]

Other uses

Caffeic acid may be the active ingredient in caffenol, a do-it-yourself black-and-white photographic developer made from instant coffee.[21] The developing chemistry is similar to that of Catechol or Pyrogallol.[22]

It is also used as a matrix in MALDI mass spectrometry analyses.[23]

References

  1. ^ Kevin S. Gould, Kenneth R. Markham, Richard H. Smith and Jessica J. Goris, (2000). "Functional role of anthocyanins in the leaves of Quintinia serrata A. Cunn.". Journal of Experimental Botany 51 (347): 1107–1115. doi:10.1093/jexbot/51.347.1107. PMID 10948238. http://jxb.oxfordjournals.org/cgi/content/full/51/347/1107. 
  2. ^ Wout Boerjan, John Ralph, Marie Baucher Annual Reviews Plant Biology 2003, volume 54, 519–46. doi:10.1146/annurev.arplant.54.031902.134938.
  3. ^ Red Clover Flowers Herbal Information
  4. ^ "Dr. Duke's Phytochemical and Ethnobotanical Databases". http://www.ars-grin.gov/cgi-bin/duke/chemical.pl?CAFFEICACID. 
  5. ^ a b Olthof MR, Hollman PC, Katan MB (January 2001). "Chlorogenic acid and caffeic acid are absorbed in humans". J. Nutr. 131 (1): 66–71. PMID 11208940. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=11208940. 
  6. ^ "Nuts’New Aflatoxin Fighter: Caffeic Acid?". http://www.ars.usda.gov/is/AR/archive/oct06/nuts1006.htm. 
  7. ^ 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 (1): 207–212. doi:10.1093/carcin/19.1.207. PMID 9472713. http://carcin.oxfordjournals.org/cgi/reprint/19/1/207.pdf. 
  8. ^ "Caffeic Acid (IARC Summary & Evaluation, Volume 56, 1993)". http://www.inchem.org/documents/iarc/vol56/03-caff.html. 
  9. ^ MA Peppercorn and P Goldman (1972). "Caffeic acid metabolism by gnotobiotic rats and their intestinal bacteria". Proceedings of the National Academy of Sciences 69 (6): 1413–1415. doi:10.1073/pnas.69.6.1413. PMC 426714. PMID 4504351. http://www.pnas.org/cgi/content/abstract/69/6/1413. 
  10. ^ M-P Gonthier, M-A Verny, C Besson, C Rémésy and A Scalbert (1 June 2003). "Chlorogenic acid bioavailability largely depends on its metabolism by the gut microflora in rats". Journal of Nutrition 133 (6): 1853–1859. PMID 12771329. http://jn.nutrition.org/cgi/content/full/133/6/1853. 
  11. ^ Chung TW, Moon SK, Chang YC, et al. (November 2004). "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". FASEB J. 18 (14): 1670–81. doi:10.1096/fj.04-2126com. PMID 15522912. http://www.fasebj.org/cgi/pmidlookup?view=long&pmid=15522912. 
  12. ^ Demestre M, Messerli SM, Celli N, et al. (August 2008). "CAPE (caffeic acid phenethyl ester)-based propolis extract (Bio 30) suppresses the growth of human neurofibromatosis (NF) tumor xenografts in mice". Phytother Res 23 (2): 226. doi:10.1002/ptr.2594. PMID 18726924. 
  13. ^ Natarajan K, Singh S, Burke TR, Grunberger D, Aggarwal BB (August 1996). "Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B". Proc. Natl. Acad. Sci. U.S.A. 93 (17): 9090–5. doi:10.1073/pnas.93.17.9090. PMC 38600. PMID 8799159. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=8799159. 
  14. ^ Orban Z, Mitsiades N, Burke TR, Tsokos M, Chrousos GP (2000). "Caffeic acid phenethyl ester induces leukocyte apoptosis, modulates nuclear factor-kappa B and suppresses acute inflammation". Neuroimmunomodulation 7 (2): 99–105. doi:10.1159/000026427. PMID 10686520. http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=nim07099. 
  15. ^ Neradil J, Veselská R, Slanina J (2003). "UVC-protective effect of caffeic acid on normal and transformed human skin cells in vitro". Folia Biol. (Praha) 49 (5): 197–202. PMID 14680294. 
  16. ^ Staniforth V, Chiu LT, Yang NS (September 2006). "Caffeic acid suppresses UVB radiation-induced expression of interleukin-10 and activation of mitogen-activated protein kinases in mouse". Carcinogenesis 27 (9): 1803–11. doi:10.1093/carcin/bgl006. PMID 16524889. http://carcin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16524889. 
  17. ^ Huang MT, Ma W, Yen P, et al. (April 1996). "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". Carcinogenesis 17 (4): 761–5. doi:10.1093/carcin/17.4.761. PMID 8625488. http://carcin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=8625488. 
  18. ^ Huang MT, Smart RC, Wong CQ, Conney AH (November 1988). "Inhibitory effect of curcumin, chlorogenic acid, caffeic acid, and ferulic acid on tumor promotion in mouse skin by 12-O-tetradecanoylphorbol-13-acetate". Cancer Res. 48 (21): 5941–6. PMID 3139287. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=3139287. 
  19. ^ Lee WJ, Zhu BT (February 2006). "Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols". Carcinogenesis 27 (2): 269–77. doi:10.1093/carcin/bgi206. PMID 16081510. http://carcin.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=16081510. 
  20. ^ Mirzoeva OK, Calder PC (December 1996). "The effect of propolis and its components on eicosanoid production during the inflammatory response". Prostaglandins Leukot. Essent. Fatty Acids 55 (6): 441–9. doi:10.1016/S0952-3278(96)90129-5. PMID 9014224. 
  21. ^ Caffenol blog "Caffenol-C-M, recipe"
  22. ^ Williams, Scott "A Use for that Last Cup of Coffee: Film and Paper Development", Technical Photographic Chemistry 1995 Class, Imaging and Photographic Technology Department, School of Photographic Arts and Sciences Rochester Institute of Technology
  23. ^ Beavis RC, Chait BT (December 1989). "Cinnamic acid derivatives as matrices for ultraviolet laser desorption mass spectrometry of proteins". Rapid Commun. Mass Spectrom. 3 (12): 432–5. doi:10.1002/rcm.1290031207. PMID 2520223. 

External links

Hydroxycinnamic acids
Glycosides
Tartaric acid esters
Others