CAFFEIC ACID: STRUCTURE, PROPERTIES, BIOSYNTHESIS, USES - CHEMISTRY - 2024

The caffeic acid is an organic compound member catechols and phenylpropanoids. Its molecular formula is C ₉ H ₈ O ₄. It is derived from cinnamic acid and is also called 3,4-dihydroxycinnamic acid or 3- (3,4-dihydroxyphenyl) -acrylic acid.

Caffeic acid is widely distributed in plants because it is an intermediate in the biosynthesis of lignin, which is a component of the plant structure. But it is abundantly found in drinks such as coffee and its seeds.

Caffeic acid is found in coffee. Author: Engin Akyurt. Source: Pixabay.

It can protect the skin from ultraviolet rays, resulting anti-inflammatory and anti-cancer. Caffeic acid prevents atherosclerosis associated with obesity and it is believed that it can decrease the accumulation of visceral fat.

There is evidence that it can protect neurons and improve memory function, and that it could represent a new treatment for psychiatric and neurodegenerative diseases.

It has marked antioxidant properties, being the most powerful antioxidant among hydrocinnamic acids. It also has potential uses in the textile and wine industry and as an insecticide, among other applications.

Structure

Since it is a phenylpropanoid, caffeic acid has an aromatic ring with a three-carbon substituent. In the aromatic ring it has two hydroxyl groups –OH and in the three carbon chain there is a double bond and a –COOH group.

Due to the double bond, its structure can take the cis form (the dihydroxyphenyl group and the -COOH on the same side of the plane of the double bond) or trans (in totally opposite positions).

Caffeic acid molecule structure. It can be seen that -COOH and dihydroxyphenyl in this case are in the trans position. Fuse809. Source: Wikimedia Commons.

Nomenclature

- Caffeic acid

- 3,4-dihydroxycinnamic acid

- 3- (3,4-dihydroxyphenyl) -acrylic acid

- 3- (3,4-dihydroxyphenyl) -propenoic acid

Properties

Physical state

Yellow to orange crystalline solid that forms prisms or sheets.

Solid caffeic acid. Danny S.. Source: Wikimedia Commons.

Molecular weight

180.16 g / mol.

Melting point

225 ºC (melts with decomposition).

Solubility

Weakly soluble in cold water, less than 1 mg / mL at 22 ºC. Freely soluble in hot water. Very soluble in cold alcohol. Slightly soluble in ethyl ether.

Dissociation constant

pK _a = 4.62 at 25 ° C.

Chemical properties

Alkaline solutions of caffeic acid are yellow to orange in color.

Location in nature

It is found in drinks such as coffee and green mate, in blueberries, aubergines, apples and ciders, seeds and tubers. It is also found in the composition of all plants because it is an intermediate in the biosynthesis of lignin, a structural constituent of these.

It should be noted that most of the caffeic acid in edible plants is in the form of its esters combined with other constituents of the plant.

It is present as chlorogenic acid, which is found for example in coffee beans, various fruits and potatoes, and as rosmarinic acid in certain aromatic herbs.

It is sometimes found in the conjugated molecules of caffeylquinic and dicaphenylquinic acids.

In wine it is conjugated with tartaric acid; with kaphtaric acid in grapes and grape juice; in lettuce and endive in the form of chicoric acid which is dicafeiltartaric and caffeylmalic acid; in spinach and tomatoes conjugated with p-coumaric acid.

In broccoli and cruciferous vegetables it is conjugated with synapic acid. In wheat and corn bran it is found in the form of cinnamates and ferulates or feruloilquinic acid and also in citric juices.

Biosynthesis

Phenylpropanoid molecules such as caffeic acid are formed by the biosynthetic pathway of shikimic acid, via phenylalanine or tyrosine, with cinnamic acid as an important intermediate.

Furthermore, in the biosynthesis of plant lignin via the phenylpropanoid unit pathway, p-coumaric acid is converted to caffeic acid.

Utility for human health

Caffeic acid is reported to possess antioxidant and fat oxidation suppressing properties. As an antioxidant, it is one of the most powerful phenolic acids, its activity being the highest among the hydrocinnamic acids. The parts of its structure responsible for this activity are o-diphenol and hydroxycinnamyl.

It is estimated that the antioxidant mechanism passes through the formation of a quinone from the dihydroxybenzene structure, because it oxidizes much more easily than biological materials.

However, in certain studies it was found that the quinone-like structure is not stable and reacts by coupling with other structures through a peroxyl-like bond. The latter is the step that truly scavenges free radicals in the antioxidant activity of caffeic acid.

Caffeic acid is anti-inflammatory. Protects skin cells by exerting anti-inflammatory and anticancer effect when exposed to ultraviolet radiation.

Reduces DNA methylation in human cancer cells, preventing tumor growth.

It has an antiatherogenic action in atherosclerosis associated with obesity. It prevents atherosclerosis by inhibiting the oxidation of low-density lipoproteins and the production of reactive oxygen species.

Phenethyl ester of caffeic acid or phenethyl caffeate has been found to have antiviral, anti-inflammatory, antioxidant, and immunomodulatory properties. Its oral administration attenuates the atherosclerotic process.

Phenethyl coffeeate. Ed (Edgar181). Source: Wikimedia Commons.

Furthermore, this ester exerts protection of neurons against inadequate blood supply, against apoptosis induced by the low amount of potassium in the cell, and neuroprotection against Parkinson's disease and other neurodegenerative diseases.

Potential use against obesity

Some studies indicate that caffeic acid exhibits significant potential as an anti-obesity agent by suppressing lipogenic (fat-generating) enzymes and the liver accumulation of lipids.

Mice with obesity induced by a high fat diet were administered caffeic acid and, as a result, the body weight gain of the specimens was reduced, the weight of adipose tissue and the accumulation of visceral fat decreased.

Obese laboratory mice. Pogrebnoj-Alexandroff. Source: Wikimedia Commons.

In addition, the concentration of triglycerides and cholesterol in plasma and liver decreased. In other words, caffeic acid reduced fat production.

Potential use against Alzheimer's disease

Alzheimer's disease in certain individuals has been associated, among other factors, with impaired glucose metabolism and insulin resistance. Impaired insulin signaling in neurons can be associated with neurocognitive disorders.

In a recent study (2019), the administration of caffeic acid to laboratory animals with hyperinsulinemia (excess insulin) improved certain mechanisms that protect neuronal cells from the attack of oxidative stress in the hippocampus and cortex.

It also decreased the accumulation of certain compounds that cause toxicity in brain neurons.

The researchers suggest that caffeic acid may improve memory function by enhancing insulin signaling in the brain, decreasing toxin production, and retaining synaptic plasticity, or the ability of neurons to connect with each other to transmit information.

In conclusion, caffeic acid could prevent the progression of Alzheimer's disease in diabetic patients.

Potential use for other psychiatric and neurodegenerative disorders

Recent experiments (2019) show that caffeic acid has an antioxidant and reducing effect on the activation of microglia in the hippocampus of mice. Microglia is a type of cell that works by eliminating elements that are harmful to neurons by phagocytosis.

Oxidative stress and the activation of microglia favor psychiatric and neurodegenerative disorders. These pathologies include Parkinson's disease, Alzheimer's disease, schizophrenia, bipolar disorder, and depression.

Given its ability to reduce the aforementioned effects, caffeic acid could represent a new treatment for these diseases.

Other possible uses

In the textile industry

Caffeic acid is helpful in producing a stronger type of wool.

Using the enzyme tyrosinase, it has been possible to insert caffeic acid molecules into a wool protein substrate. The incorporation of this phenolic compound in the wool fiber increases the antioxidant activity, reaching up to 75%.

The wool textile fiber thus modified has new properties and characteristics that make it more resistant. The antioxidant effect does not diminish after washing the wool.

In the food industry

Caffeic acid has attracted attention for its antioxidant properties at the biological level to be used as an antioxidant in food.

In this sense, some studies show that caffeic acid is capable of retarding the oxidation of lipids in fish muscle tissue and avoiding the consumption of α-tocopherol present in it. Α-Tocopherol is a type of vitamin E.

The antioxidant action is achieved through the cooperation of ascorbic acid also present in the tissue. This caffeic acid - ascorbic acid interaction synergistically reinforces the system's resistance to oxidative damage.

In the wine industry

It has been determined that the addition of caffeic acid to red grapes of the Tempranillo variety or its wine leads to an increase in the stability of the wine color during storage.

The results indicate that intramolecular copigmentation reactions occur during the aging period that increase the stability of new molecules and that this positively influences the color of the wine.

As an insecticide

In experiments with Helicoverpa armigera, a lepidopteran insect, it has recently been found that caffeic acid has potential as an insecticide.

This insect inhabits and feeds on many types of plants and crops.

Helicoverpa armigera, an insect that attacks many types of edible plants. Dumi. Source: Wikimedia Commons.

All the functional groups of caffeic acid contribute to making it an inhibitor of protease, an enzyme found in the intestines of these insects. Furthermore, caffeic acid remains stable in the environment of the insect's intestine.

Helicoverpa armigera larva. Gyorgy Csoka, Hungary Forest Research Institute, Bugwood.org. Source: Wikimedia Commons.

By inhibiting protease, the insect cannot carry out the processes required for its growth and development, and it dies.

Its use would be an ecological way to control this type of pests.

References

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2. US National Library of Medicine. (2019). Caffeic acid. Recovered from: pubchem.ncbi.nlm.nih.gov.
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5. Joshi, RS et al. (2014). Way toward “Dietary Pesticides”: Molecular Investigation of Insecticidal Action of Caffeic Acid against Helicoverpa armigera. J. Agric. Food Chem. 2014, 62, 45, 10847-10854. Recovered from pubs.acs.org.
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7. Iglesias, J. et al. (2009). Caffeic Acid as Antioxidant in Fish Muscle: Mechanism of Synergism with Endogenous Ascorbic Acid and α-Tocopherol. Agric. Food Chem. 2009, 57, 2, 675-681. Recovered from pubs.acs.org.
8. Lee, E.-S. et al. (2012). Caffeic Acid Disturbs Monocyte Adhesion onto Cultures Endothelial Cells Stimulated by Adipokine Resistin. J. Agric. Food Chem. 2012, 60, 10, 2730-2739. Recovered from pubs.acs.org.
9. Aleixandre-Tudo, JL et al. (2013). Impact of caffeic acid addition on phenolic composition of tempranillo wines from different winemaking techniques. J. Agric. Food Chem. 2013, 61, 49, 11900-11912. Recovered from pubs.acs.org.
10. Liao, C.-C. et al. (2013). Prevention of Diet-Induced Hyperlipidemia and Obesity by Caffeic Acid in C57BL / 6 Mice Through Regulation of Hepatic Lipogenesis Gene Expression. J. Agric. Food Chem. 2013, 61, 46, 11082-11088. Recovered from pubs.acs.org.