Caffeic acid is anorganic compound with the formula(HO)2C6H3CH=CHCO2H. It is a polyphenol with a key role in scavengingreactive oxygen species (ROS) generated in energy metabolism. Caffeic acid is also one major polyphenol responsible for maintaining normal levels ofnitric oxide (NO) within cells. Caffeic acid is a yellow, solid chemical compound that is structually classified as ahydroxycinnamic acid, and the molecule consists of bothphenolic andacrylic functional groups. Caffeic acid is found in all plants as an intermediate in thebiosynthesis oflignin, a naturally occurring complexcarbohydrate representing the principal components ofbiomass and its residues.[2] It is chemically unrelated tocaffeine; instead, the shared name is related to its presence incoffee.
Free caffeic acid can be found in a variety of beverages, including brewedcoffee at 63.1-96.0 mg per 100 ml[7] and red wine at 2 mg per 100 ml.[8] It is found at relatively high levels in herbs of the mint family, especiallythyme,sage andspearmint (at about 20 mg per 100 g), and in spices, such asCeylon cinnamon andstar anise (at about 22 mg per 100 g). Caffeic acid occurs at moderate levels insunflower seeds (8 mg per 100 g),apple sauce,apricots andprunes (at about 1 mg per 100 g).[9] It occurs at remarkably high levels inblack chokeberry (141 mg per 100 g).[10] It is also quite high in the South American herbyerba mate (150 mg per 100 g based onthin-layer chromatographydensitometry[11] and HPLC[12]). It is also found at lower levels inbarley andrye.[13]
In plants, caffeic acid (middle) is formed from 4-hydroxycinnamic acid (left) and is transformed toferulic acid.
Dihydroxyphenylalanine ammonia-lyase was presumed to use3,4-dihydroxy-L-phenylalanine (L-DOPA) to produce trans-caffeate and NH3. However, the EC number for this purported enzyme was deleted in 2007, as no evidence has emerged for its existence.[17]
Caffeic acid is susceptible toautoxidation.Glutathione andthiol compounds (cysteine,thioglycolic acid orthiocresol) orascorbic acid have a protective effect on browning and disappearance of caffeic acid.[19] This browning is due to the conversion ofo-diphenols into reactiveo-quinones. Chemical oxidation of caffeic acid in acidic conditions usingsodium periodate leads to the formation of dimers with a furan structure (isomers of 2,5-(3′,4′-dihydroxyphenyl)tetrahydrofuran 3,4-dicarboxylic acid).[20] Caffeic acid can also be polymerized using thehorseradish peroxidase/H2O2 oxidizing system.[21]
Caffeic acid has a variety of potential pharmacological effects inin vitro studies and in animal models, and the inhibitory effect of caffeic acid on cancer cell proliferation by an oxidative mechanism in the humanHT-1080fibrosarcoma cell line has recently been established.[23]
Caffeic acid is anantioxidantin vitro and alsoin vivo.[16] Caffeic acid also shows immunomodulatory andanti-inflammatory activity. Caffeic acid outperformed the other antioxidants, reducingaflatoxin production by more than 95 percent. The studies are the first to show that oxidative stress that would otherwise trigger or enhanceAspergillus flavus aflatoxin production can be stymied by caffeic acid. This opens the door to use as a naturalfungicide by supplementing trees with antioxidants.[24]
Studies of thecarcinogenicity of caffeic acid have mixed results. Some studies have shown that it inhibitscarcinogenesis, and other experiments show carcinogenic effects.[25] Oral administration of high doses of caffeic acid in rats has causedstomachpapillomas.[25] In the same study, high doses of combined antioxidants, including caffeic acid, showed a significant decrease in growth ofcolontumors in those same rats. No significant effect was noted otherwise. Caffeic acid is listed under some Hazard Data sheets as a potential carcinogen,[26] as has been listed by theInternational Agency for Research on Cancer as aGroup 2B carcinogen ("possibly carcinogenic to humans").[27] More recent data show thatbacteria in the rats' guts may alter the formation ofmetabolites of caffeic acid.[28][29] Other than caffeic acid being athiamine antagonist (antithiamine factor), there have been no known ill effects of caffeic acid in humans.Also, caffeic acid treatment attenuated lipopolysaccharide (LPS)-induced sickness behaviour in experimental animals by decreasing both peripheral and centralcytokine levels along with oxidative stress inflicted by LPS.[30]
^Santos, Sónia A. O.; Freire, Carmen S. R.; Domingues, M. Rosário M.; Silvestre, Armando J. D.; Pascoal Neto, Carlos (2011). "Characterization of Phenolic Components in Polar Extracts of Eucalyptus globulus Labill. Bark by High-Performance Liquid Chromatography–Mass Spectrometry".Journal of Agricultural and Food Chemistry.59 (17):9386–9393.Bibcode:2011JAFC...59.9386S.doi:10.1021/jf201801q.PMID21761864.
^Choudhary, M. Iqbal; Naheed, Nadra; Abbaskhan, Ahmed; Musharraf, Syed Ghulam; Siddiqui, Hina; Atta-Ur-Rahman (2008). "Phenolic and other constituents of fresh water fernSalvinia molesta".Phytochemistry.69 (4):1018–1023.Bibcode:2008PChem..69.1018C.doi:10.1016/j.phytochem.2007.10.028.PMID18177906.
^Pirjo, Mittila; Kumpulainen, Jorma (19 June 2002). "Determination of free and total phenolic acids in plant-derived foods by HPLC with diode-array detection".J Agric Food Chem.50 (13):3660–7.Bibcode:2002JAFC...50.3660M.doi:10.1021/jf020028p.PMID12059140.
^Zheng, Wei; Wang, Shiow Y (15 January 2003). "Oxygen radical absorbing capacity of phenolics in blueberries, cranberries, chokeberries, and lingonberries".J Agric Food Chem.51 (2):502–9.Bibcode:2003JAFC...51..502Z.doi:10.1021/jf020728u.PMID12517117.
^Berté, Kleber A. S. (2011). "Chemical Composition and Antioxidant Activity of Yerba-Mate (Ilex paraguariensis A. St.-Hil., Aquifoliaceae) Extract as Obtained by Spray Drying".Journal of Agricultural and Food Chemistry.59 (10):5523–5527.Bibcode:2011JAFC...59.5523B.doi:10.1021/jf2008343.PMID21510640.
^Quinde-Axtell, Zory; Baik, Byung-Kee (2006). "Phenolic Compounds of Barley Grain and Their Implication in Food Product Discoloration".J. Agric. Food Chem.54 (26):9978–9984.Bibcode:2006JAFC...54.9978Q.doi:10.1021/jf060974w.PMID17177530.
^Cilliers, Johannes J. L.; Singleton, Vernon L. (1990). "Caffeic acid autoxidation and the effects of thiols".J. Agric. Food Chem.38 (9):1789–1796.Bibcode:1990JAFC...38.1789C.doi:10.1021/jf00099a002.
^Fulcrand, Hélène; Cheminat, Annie; Brouillard, Raymond; Cheynier, Véronique (1994). "Characterization of compounds obtained by chemical oxidation of caffeic acid in acidic conditions".Phytochemistry.35 (2):499–505.Bibcode:1994PChem..35..499F.doi:10.1016/S0031-9422(00)94790-3.
^Maier, V. P.; Metzler, D. M.; Huber, A. F. (1964). "3-O-Caffeoylshikimic acid (dactylifric acid) and its isomers, a new class of enzymic browning substrates".Biochemical and Biophysical Research Communications.14 (2):124–128.Bibcode:1964BBRC...14..124M.doi:10.1016/0006-291x(64)90241-4.PMID5836492.
^Rajendra Prasad, N.; Karthikeyan, A.; Karthikeyan, S.; Reddy, B. V. (Mar 2011). "Inhibitory effect of caffeic acid on cancer cell proliferation by oxidative mechanism in human HT-1080 fibrosarcoma cell line".Mol Cell Biochem.349 (1–2):11–19.doi:10.1007/s11010-010-0655-7.PMID21116690.S2CID28014579.
^Beavis, R. C.; Chait, B. T. (Dec 1989). "Cinnamic acid derivatives as matrices for ultraviolet laser desorption mass spectrometry of proteins".Rapid Commun. Mass Spectrom.3 (12):432–435.Bibcode:1989RCMS....3..432B.doi:10.1002/rcm.1290031207.PMID2520223.
