Protocatechuic acid (PCA) is a

dihydroxybenzoic acid Dihydroxybenzoic acids (DHBA) are a type of phenolic acids. There are six main compounds, having all the same molecular formula C7H6O4. Those are: * 2,3-Dihydroxybenzoic acid (2-Pyrocatechuic acid or hypogallic acid) * 2,4-Dihydroxybenzoic acid ...

, a type of phenolic acid. It is a major metabolite of antioxidant polyphenols found in green tea. It has mixed effects on normal and cancer cells in ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' and ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'' studies.

Biological effects

Protocatechuic acid (PCA) is antioxidant and anti-inflammatory. PCA extracted from ''Hibiscus sabdariffa'' protected against chemically induced liver toxicity ''in vivo''. ''In vitro'' testing documented antioxidant and anti-inflammatory activity of PCA, while liver protection ''in vivo'' was measured by chemical markers and histological assessment. PCA has been reported to induce

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

of human

leukemia Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ' ...

cells, as well as malignant HSG1 cells taken from human oral cavities, but PCA was found to have mixed effects on TPA-induced mouse skin tumours. Depending on the amount of PCA and the time before application, PCA could reduce or enhance tumour growth. Similarly, PCA was reported to increase proliferation and inhibit apoptosis of neural

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can differentiate into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type o ...

s. In an ''in vitro'' model using

HL-60 The HL-60 cell line is a human leukemia cell line that has been used for laboratory research on blood cell formation and physiology. HL-60 proliferates continuously in suspension culture in nutrient and antibiotic chemicals. The doubling time is ...

cells, protocatechuic acid showed an antigenotoxic effect and tumoricidal activity. In two preclinical investigations, protocatechuic acid from ''

Hibiscus sabdariffa Roselle (''Hibiscus sabdariffa'') is a species of flowering plant in the genus ''Hibiscus'' that is native to Africa, most likely West Africa and also found in India especially Maharashtra with local name ambali. In the 16th and early 17th cent ...

'' showed an excellent ability to effectively inhibit the replication of herpes simplex virus type 2 and to potently deactivate the catalytic activity of

urease Ureases (), functionally, belong to the superfamily of amidohydrolases and phosphotriesterases. Ureases are found in numerous bacteria, fungi, algae, plants, and some invertebrates, as well as in soils, as a soil enzyme. They are nickel-containin ...

Occurrence in nature

Protocatechuic acid can be isolated from the stem bark of ''

Boswellia dalzielii ''Boswellia dalzielii'' is a tree species in the genus ''Boswellia'' found in Africa. The bark of this plant is used in traditional medicines. Gallic and protocatechuic acids were isolated as the main antibacterial and antioxidant principles of ...

''. and from leaves of ''

Diospyros melanoxylon ''Diospyros melanoxylon'', the Coromandel ebony or East Indian ebony, is a species of flowering tree in the family Ebenaceae native to India and Sri Lanka; it has a hard, dry bark. Its common name derives from Coromandel, the coast of southeas ...

''. The hardening of the protein component of

insect cuticle The cuticle forms the major part of the integument of the Arthropoda. It includes most of the material of the exoskeleton of the insects, Crustacea, Arachnida, and Myriapoda. Morphology In arthropods, the integument, the external "skin", or "s ...

has been shown to be due to the tanning action of an agent produced by oxidation of a phenolic substance. In the analogous hardening of the cockroach

ootheca An ootheca (pl. ''oothecae'' ) is a type of egg mass made by any member of a variety of species including mollusks (such as ''Turbinella laevigata''), mantises, and cockroaches. The word is a Latinized combination of ''oo-'', meaning "egg", f ...

, the phenolic substance concerned is protocatechuic acid.

In foods

Açaí oil Açaí oil is obtained from the fruit of ''Euterpe oleracea'' (açaí palm), which grows in the Amazon rainforest. The oil is rich in phenolic compounds similar in profile to the pulp itself, such as vanillic acid, syringic acid, p-hydroxybenzoic a ...

, obtained from the fruit of the

açaí palm The açaí palm (, , from Nheengatu ''asai''), ''Euterpe oleracea,'' is a species of palm tree (Arecaceae) cultivated for its fruit (açaí berries, or simply açaí), hearts of palm (a vegetable), leaves, and trunk wood. Global demand for the f ...

(''Euterpe oleracea''), is rich in protocatechuic acid (). Protocatechuic acid also exists in the skins of some strains of onion as an antifungal mechanism, increasing endogenous resistance against smudge fungus. It is also found in ''

Allium cepa An onion (''Allium cepa'' L., from Latin ''cepa'' meaning "onion"), also known as the bulb onion or common onion, is a vegetable that is the most widely cultivated species of the genus ''Allium''. The shallot is a botanical variety of the onion ...

'' (17,540 ppm). PCA occurs in roselle (''Hibiscus sabdariffa''), which is used worldwide as a food and beverage. Protocatechuic acid is also found in mushrooms such as ''

Agaricus bisporus ''Agaricus bisporus'' is an edible basidiomycete mushroom native to grasslands in Eurasia and North America. It has two color states while immature – white and brown – both of which have various names, with additional names for the mature ...

'' or ''

Phellinus linteus ''Phellinus linteus'' (Japanese "meshimakobu", Chinese "song gen", Korean "sanghwang", English "mesima", American English "black hoof mushroom") is a mushroom. It is shaped like a hoof, has a bitter taste, and in the wild grows on mulberry tree ...

''. PCA is regarded as an active component in traditional Chinese herbal medicine such as Stenoloma chusanum (L.) Ching, Ilex chinensis Sims, Cibotium barometz (L.) J.Sm.

Metabolism

Protocatechuic acid is one of the main catechins

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s found in humans after consumption of

green tea Green tea is a type of tea that is made from '' Camellia sinensis'' leaves and buds that have not undergone the same withering and oxidation process which is used to make oolong teas and black teas. Green tea originated in China, and since the ...

infusions.

Enzymes

;Biosynthesis enzymes *

3-dehydroshikimate dehydratase 3-dehydroshikimate dehydratase () is an enzyme with systematic name ''3-dehydroshikimate hydro-lyase''. This enzyme catalyses the following chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic tr ...

* (3''S'',4''R'')-3,4-dihydroxycyclohexa-1,5-diene-1,4-dicarboxylate dehydrogenase * terephthalate 1,2-''cis''-dihydrodiol dehydrogenase *

3-hydroxybenzoate 4-monooxygenase In enzymology, a 3-hydroxybenzoate 4-monooxygenase () is an enzyme that catalyzes the chemical reaction :3-hydroxybenzoate + NADPH + H+ + O2 \rightleftharpoons 3,4-dihydroxybenzoate + NADP+ + H2O The 4 substrates of this enzyme are 3-hydroxyb ...

* 4-hydroxybenzoate 3-monooxygenase (NAD(P)H) * 4-sulfobenzoate 3,4-dioxygenase * vanillate monooxygenase * 3,4-dihydroxyphthalate decarboxylase * 4,5-dihydroxyphthalate decarboxylase Protocatechuic biosynthesis

; Degradation enzymes * The enzyme protocatechuate decarboxylase uses 3,4-dihydroxybenzoate to produce

catechol Catechol ( or ), also known as pyrocatechol or 1,2-dihydroxybenzene, is a toxic organic compound with the molecular formula . It is the ''ortho'' isomer of the three isomeric benzenediols. This colorless compound occurs naturally in trace amoun ...

and CO₂. * The enzyme

protocatechuate 3,4-dioxygenase In enzymology, a protocatechuate 3,4-dioxygenase () is an enzyme that catalyzes the chemical reaction : 3,4-dihydroxybenzoate + O2 \rightleftharpoons 3-carboxy-cis,cis-muconate Thus, the two substrates of this enzyme are 3,4-dihydroxybenzoate ( ...

uses 3,4-dihydroxybenzoate and O₂ to produce 3-carboxy-''cis'',''cis''-muconate.

References