Ellagic acid structure, properties, obtaining, location, uses

2690
Simon Doyle
Ellagic acid structure, properties, obtaining, location, uses

The ellagic acid is a tetracyclic organic compound whose chemical formula is C14H6OR8. It is a polyphenol, being the dimer of gallic acid. It is also known as benzoaric acid. It is a yellow or cream colored crystalline solid, very stable against temperature. It is a weak acid very slightly soluble in water but soluble in basic or alkaline medium..

It is found distributed in the vegetable kingdom contained in various fruits, such as pomegranate, grapes, nuts and in drinks such as wine and tea. It is abundant in wood and woody debris.

Pomegranates, fruits rich in ellagic acid. Authors: Peggy und Marco Lachmann-Anke. Source: Pixabay.

It has several important biological properties: antioxidant, anti-inflammatory, anticancer, antimutagenic, protects the liver and reduces the level of fats in the blood plasma. It exerts a protective effect on neurons and favors the generation of insulin.

It acts synergistically with other natural polyphenols. For this reason, the whole pomegranate fruit is much more effective as an antioxidant and anticancer than ellagic acid alone..

Although it is not easily absorbed by the human intestine, its derivative compounds or metabolites are, also performing its antioxidant properties.

Article index

  • 1 Structure
  • 2 Nomenclature
  • 3 Properties
    • 3.1 Physical state
    • 3.2 Molecular weight
    • 3.3 Melting point
    • 3.4 Density
    • 3.5 Solubility
    • 3.6 Dissociation constants
    • 3.7 Chemical properties
  • 4 Obtaining in the laboratory
  • 5 Location in nature
  • 6 Uses in medicine
    • 6.1 Liver protection
    • 6.2 Protection against Alzheimer's disease
    • 6.3 Against diabetes
    • 6.4 Against gallbladder cancer
    • 6.5 Synergistic effect against leukemia
    • 6.6 Potential against Parkinson's disease
    • 6.7 In the prevention of gastritis and gastric ulcers
    • 6.8 Disadvantages of its oral administration and how they can be solved
    • 6.9 Ellagic acid metabolites
  • 7 References

Structure

Ellagic acid has four cyclic structures fused together. It also has four phenolic -OH groups and two lactone-like structures.

Structure of the ellagic acid molecule where phenolic and lactone groups are observed. Author: Yikrazuul. Source: Own work. Source: Wikimedia Commons.

Nomenclature

- Ellagic acid.

- Benzoaric acid.

- 4,4 ', 5,5', 6,6'-hexahydroxydiphenic acid-2,6,2 ', 6'-dilactone.

Properties

Physical state

Cream or yellow solid that crystallizes in the shape of needles.

Molecular weight

302.19 g / mol.

Melting point

Greater than 360 ºC (it is highly thermostable).

Density

1,667 g / cm3 at 18 ºC.

Solubility

Weakly soluble in water: less than 1 mg / mL at 21 ºC. Less than 10 mg / mL at pH 7.4. Weakly soluble in ethyl alcohol.

Soluble in alkaline medium and in pyridine. Practically insoluble in ethyl ether.

Dissociation constants

It has four phenolic -OH groups. Here is the tendency to dissociate from each of these:

pKa1 = 6.69; pKa2 = 7.45; pKa3 = 9.61; pKa4 = 11.50.

Chemical properties

It is a weak acid, which ionizes at a physiological pH.

It has four rings that represent the lipophilic or hydrophobic part of the molecule. It has four phenolic groups and two lactone groups that are the hydrophilic or water-related part.

Obtaining in the laboratory

Certain researchers carried out in the laboratory the synthesis of ellagic acid starting from methyl gallate by oxidative coupling, through the formation of α-pentagaloylglucose..

Location in nature

Ellagic acid is a very common compound in plants. It is very abundant in fruits such as pomegranate, berries, strawberries, raspberries, blackberries, grapes, persimmon, peach, plum, walnuts, almonds and in drinks such as wine and tea.

Fruits that contain ellagic acid. Author: Andreas N. Source: Pixabay.

In grapes it is more abundant in the skin of the fruit than in the pulp, and it is more abundant in the pulp than in the juice. The more the grape ripens, the higher the ellagic acid content.

It can be found in its free form or more commonly in conjugated form with glycosides (such as xylose and glucose) or as part of ellagitannins (polymeric molecules).

The various varieties of tea are a significant source of ellagic acid in the form of ellagitannins..

Infusion of tea, a drink that contains ellagic acid. Author: Dungthuyvunguyen. Source: Pixabay.

Ellagitanins are bioactive polyphenols that are not absorbed intact by the human intestine, but can be hydrolyzed to ellagic acid by the gastrointestinal flora of the colon..

All woods contain ellagic acid, which is one of the causes of the antioxidant effect of spirits aged or aged in wooden barrels. It is abundantly present in whiskey.

Woody debris such as sawdust or wood chips are rich natural sources of ellagic acid.

Uses in medicine

It is considered a compound with several biological activities: anticancer, antioxidant, antimutagenic, anti-inflammatory and cardioprotective.

It inhibits the growth of microorganisms, as it sequesters metal ions that are critical for the metabolism and growth of microbes. Acts as a free radical scavenger and antiviral.

It is believed that it could have potential in the prevention of certain chronic diseases. In addition, it inhibits wrinkles caused by UV rays.

It is such a good antioxidant that during plastic surgery small amounts of ellagic acid are applied to the skin to prevent necrosis..

It is a stimulator of immune functions and its joint administration has been proposed in chemotherapy of patients with prostate cancer..

It has antiproliferative activity against skin, esophageal and colon cancer, slows down the cell cycle and induces apoptosis of malignant cells. Acts in various DNA maintenance reactions preventing genome instability that otherwise leads to cancer.

Liver protection

It is antihepatotoxic, antisteatotic, anticolestatic, antifibrogenic, antihepatocarcinogenic and antiviral.

Hepatotoxicity refers to liver dysfunction or damage associated with exposure to drugs or substances foreign to the body. Steatosis is fatty liver disease. Cholestasis is the interruption of the flow of bile into the duodenum. Liver fibrosis is an exaggerated repair of tissues subject to chronic damage.

Drawing of human liver. Author: VSRao. Source: Pixabay.

Ellagic acid inhibits alcohol-induced liver cell damage by increasing antioxidant levels, eliminating free radicals and stabilizing cell membranes..

Reduces the level of lipids in the circulation, preventing their peroxidation. Reduces plasma cholesterol. Inhibits protease activity in liver pathogenic viruses, preventing their proliferation.

Protection against Alzheimer's disease

It exerts a neuroprotective effect by improving the symptoms of Alzheimer's disease caused by the accumulation in the brain of advanced glycation end products, which is the reaction between sugars and proteins that leads to the aging of cells.

Against diabetes

It acts on the β cells of the pancreas, stimulating insulin secretion and reducing glucose intolerance.

Against gallbladder cancer

Ellagic acid has an antiproliferation effect on cancer cells in gallbladder cancer. Inhibits tumor invasion and chemotaxis, which is the reaction of cells against chemicals.

Significantly reduces tumor growth rate, infiltrating behavior, and tumor-associated angiogenesis or blood vessel formation.

Therefore, it is considered to have potential as an adjunct therapy in the treatment of gallbladder cancer..

Synergistic effect against leukemia

Ellagic acid acts synergistically with certain flavonoids such as quercetin, present in fruits and vegetables, to inhibit cell growth and promote apoptosis in leukemia cells.

Synergy is a phenomenon that in this case means that the effect produced by several chemical compounds together is greater than the result of the individual sum.

This effect increases even more in the presence of resveratrol, another polyphenol present in many plants, fruits and vegetables..

Ellagic acid is one of the most powerful phytochemicals found in the pomegranate fruit, but certain studies indicate that it is not as strong as the pomegranate itself, since in the whole fruit there are a series of chemical compounds that act synergistically. with ellagic acid as anticancer and antioxidant.

Potential against Parkinson's disease

Certain researchers have found that ellagic acid protects cells from some mechanisms that lead to their degeneration.

Eliminates NO radicalsx (which are involved in the generation of Parkinson's), decreases the mechanism of formation of reactive oxygen species and reactive nitrogen species and imparts antiapoptosis properties.

It thus exerts a neuroprotective effect. It can also bind to human serum albumin.

These results indicate that ellagic acid can provide support in overcoming Parkinson's through a prophylactic or disease prevention approach..

In the prevention of gastritis and gastric ulcers

Ellagic acid present in matured whiskey has been experimentally determined to prevent alcohol-induced gastritis. Exerts a gastroprotective effect against gastric lesions.

Ellagic acid is transferred from the wood of the barrels to alcoholic beverages during their maturation in the barrels. Author: Skeeze. Source: Pixabay.

In addition, a study showed that it protects the body from alcohol toxicity, by reducing certain enzymes and increasing the antioxidant mechanism.

Its effect appears to be multifactorial in the healing of gastric ulcers. This makes it a good candidate for developing a multipurpose anti-ulcer drug..

Disadvantages of its oral administration and how they can be solved

Although ellagic acid exhibits good antioxidant activity, it has solubility problems in aqueous medium and therefore has low bioavailability when administered orally..

It is very poorly absorbed and is rapidly eliminated from the body, which limits its potential as an antioxidant due to its inability to reach adequate concentrations in tissues..

Its low bioavailability is attributed to several factors: (1) its low solubility in water, (2) it is metabolized by microorganisms in the gastrointestinal tract, (3) it is rapidly eliminated from the body due to its short half-life in plasma, ( 4) irreversibly binds to cellular DNA and proteins.

However, it has been found that supplying it in the form of a complex with phospholipids increases its bioavailability and antioxidant activity. Phospholipid complex has better nutritional efficacy for a longer period of time than ellagic acid alone.

Ellagic acid metabolites

After the consumption of foods rich in ellagitannins, in the gastrointestinal tract these are hydrolyzed to ellagic acid by the bacteria that produce the enzyme tannase..

The lactone rings of ellagic acid open, then decarboxylation and then dehydroxylation occurs through enzymatic reactions and various urolithins are formed by certain bacteria in the colon. Finally urolithin A and B are obtained.

Urolithin A, a metabolite generated by the action of intestinal bacteria on ellagic acid. Author: Kopiersperre. Source: Own work. Source: Wikimedia Commons.
Urolithin B, another metabolite generated by microorganisms in the colon from ellagic acid. Author: Kopiersperre. Source: Own work. Source: Wikimedia Commons.

These metabolites are absorbed by the intestine and reach the blood plasma.

These urolithins are believed to have anti-estrogenic, anti-aging, and anti-inflammatory biological effects. They have also been found to have an effect against melanoma or skin cancer, as they inhibit the formation of melanin and inhibit the activity of enzymes that promote melanoma..

References

  1. Lansky, E.P. (2006). Beware of Pomegranates Bearing 40% Ellagic Acid. J. Med. Food 9 (1) 2006, 119-122. Recovered from ncbi.nlm.nih.gov.
  2. U.S. National Library of Medicine. (2019). Ellagic acid. Recovered from: pubchem.ncbi.nlm.nih.gov.
  3. Derosa, G. et al. (2016). Ellagic Acid and Its Role in Chronic Diseases. Advances in Experimental Medicine and Biology 2016; 928: 473-479. Recovered from ncbi.nlm.nih.gov.
  4. Wang, S.-T. et al. (2017). Anti-melanogenic effect of urolithin A and urolithin B, the colonic metabolites of ellagic acid, in B16 melanoma cells. J. Agric. Food Chem. 2017, 65, 32, 6870-6876. Recovered from pubs.acs.org.
  5. Tomas-Barberan, F.A. and Yang, X. (2019). Tea is a significant dietary source of ellagitannins and ellagic acid. J. Agric. Food Chem. 2019, 67, 19, 5394-5404. Recovered from pubs.acs.org.C
  6. Ceci, C. et al. (2016). Ellagic Acid Inhibits Bladder Cancer Invasiveness and In Vivo Tumor Growth. Nutrients 2016, 8 (11), 744. Recovered from ncbi.nlm.nih.gov.
  7. Kabiraj, P. et al. (2014) Ellagic Acid Mitigates SON-PDI Induced Aggregation of Parkinsonian Biomarkers. ACS Chemical Neroscience 2014, 5, 12, 1209-1220. Recovered from pubs.acs.org.
  8. Selhorst e Silva Beserra, A.M. et al. (2011). Gastroprotective and Ulcer-Healing Mechanisms of Ellagic Acid in Experimental Rats. J. Agric. Food Chem. 2011, 59, 13, 6957-6965. Recovered from pubs.acs.org.
  9. Murugan, V. et al. (2009) Enhanced Oral Bioavailability and Antioxidant Profile of Ellagic Acid by Phospholipids. J. Agric. Food Chem. 2009, 57, 11, 4559-4565. Recovered from pubs.acs.org.
  10. Lee, J.-H. and Talcott, S.T. (2004). Fruit Maturity and Juice Extraction Influences Ellagic Acid Derivatives and Other Antioxidant Polyphenolics in Muscadine Grapes. J. Agric. Food Chem. 2004, 52 (2): 361-6. Recovered from ncbi.nlm.nih.gov.
  11. Ren, Y. et al. (2012). Synthesis and Antitumor Activity of Ellagic Acid Peracetate. ACS Medicinal Chemistry Letters 2012, 3, 631-636. Recovered from pubs.acs.org.

Yet No Comments