Caffeic acid is an organic compound with the formula Template:Chem2. It is a polyphenol with a key role in scavenging reactive oxygen species (ROS) generated in energy metabolism. Caffeic acid is also one major polyphenol responsible for maintaining normal levels of nitric oxide (NO) within cells. Caffeic acid is a yellow, solid chemical compound that is structually classified as a hydroxycinnamic acid, and the molecule consists of both phenolic and acrylic functional groups. Caffeic acid is found in all plants as an intermediate in the biosynthesis of lignin, a naturally occurring complex carbohydrate representing the principal components of biomass and its residues.[1] It is chemically unrelated to caffeine; instead, the shared name is related to its presence in coffee.
Free caffeic acid can be found in a variety of beverages, including brewed coffee at 63.1-96.0 mg per 100 ml[6] and red wine at 2 mg per 100 ml.[7] It is found at relatively high levels in herbs of the mint family, especially thyme, sage and spearmint (at about 20 mg per 100 g), and in spices, such as Ceylon cinnamon and star anise (at about 22 mg per 100 g). Caffeic acid occurs at moderate levels in sunflower seeds (8 mg per 100 g), apple sauce, apricots and prunes (at about 1 mg per 100 g).[8] It occurs at remarkably high levels in black chokeberry (141 mg per 100 g).[9] It is also quite high in the South American herb yerba mate (150 mg per 100 g based on thin-layer chromatographydensitometry[10] and HPLC [11]). It is also found at lower levels in barley and rye.[12]
File:CaffeicAcIn.pngIn plants, caffeic acid (middle) is formed from 4-hydroxycinnamic acid (left) and is transformed to ferulic acid.
Dihydroxyphenylalanine ammonia-lyase was presumed to use 3,4-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.[16]
Caffeic acid is susceptible to autoxidation. Glutathione and thiol compounds (cysteine, thioglycolic acid or thiocresol) or ascorbic acid have a protective effect on browning and disappearance of caffeic acid.[18] This browning is due to the conversion of o-diphenols into reactive o-quinones. Chemical oxidation of caffeic acid in acidic conditions using sodium periodate leads to the formation of dimers with a furan structure (isomers of 2,5-(3′,4′-dihydroxyphenyl)tetrahydrofuran 3,4-dicarboxylic acid).[19] Caffeic acid can also be polymerized using the horseradish peroxidase/H2O2 oxidizing system.[20]
Caffeic acid has a variety of potential pharmacological effects in in vitro studies and in animal models, and the inhibitory effect of caffeic acid on cancer cell proliferation by an oxidative mechanism in the human HT-1080fibrosarcoma cell line has recently been established.[22]
Caffeic acid is an antioxidantin vitro and also in vivo.[15] Caffeic acid also shows immunomodulatory and anti-inflammatory 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 use as a natural fungicide by supplementing trees with antioxidants.[23]
Studies of the carcinogenicity of caffeic acid have mixed results. Some studies have shown that it inhibits carcinogenesis, and other experiments show carcinogenic effects.[24] Oral administration of high doses of caffeic acid in rats has caused stomachpapillomas.[24] In the same study, high doses of combined antioxidants, including caffeic acid, showed a significant decrease in growth of colontumors in those same rats. No significant effect was noted otherwise. Caffeic acid is listed under some Hazard Data sheets as a potential carcinogen,[25] as has been listed by the International Agency for Research on Cancer as a Group 2B carcinogen ("possibly carcinogenic to humans").[26] More recent data show that bacteria in the rats' guts may alter the formation of metabolites of caffeic acid.[27][28] Other than caffeic acid being a thiamine 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 central cytokine levels along with oxidative stress inflicted by LPS.[29]
