Protocatechuic acid explained

Protocatechuic acid (PCA) is a 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 and in vivo studies.^[1]

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.^[2]

PCA has been reported to induce apoptosis of human leukemia cells, as well as malignant HSG1 cells taken from human oral cavities,^[3] 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.^[4] Similarly, PCA was reported to increase proliferation and inhibit apoptosis of neural stem cells.^[5] In an in vitro model using HL-60 leukemia cells, protocatechuic acid showed an antigenotoxic effect and tumoricidal activity.^[6] In two preclinical investigations, protocatechuic acid from Hibiscus sabdariffa showed an excellent ability to effectively inhibit the replication of herpes simplex virus type 2^[7] and to potently deactivate the catalytic activity of urease.^[8]

Occurrence in nature

Protocatechuic acid can be isolated from the stem bark of Boswellia dalzielii.^[9] and from leaves of Diospyros melanoxylon.^[10]

The hardening of the protein component of insect cuticle 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, the phenolic substance concerned is protocatechuic acid.^[11]

In foods

Açaí oil, obtained from the fruit of the açaí palm (Euterpe oleracea), is rich in protocatechuic acid .^[12] 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 (17,540 ppm).^[13]

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^[14] or Phellinus linteus.^[15]

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.^[16]

Metabolism

Protocatechuic acid is one of the main catechins metabolites found in humans after consumption of green tea infusions.^[17]

Enzymes

Biosynthesis enzymes

• 3-dehydroshikimate dehydratase
  • • • (3S,4R)-3,4-dihydroxycyclohexa-1,5-diene-1,4-dicarboxylate dehydrogenase terephthalate 1,2-cis-dihydrodiol dehydrogenase 3-hydroxybenzoate 4-monooxygenase 4-hydroxybenzoate 3-monooxygenase (NAD(P)H)
  • 4-sulfobenzoate 3,4-dioxygenase vanillate monooxygenase
• 3,4-dihydroxyphthalate decarboxylase
• 4,5-dihydroxyphthalate decarboxylase

Degradation enzymes

• The enzyme protocatechuate decarboxylase uses 3,4-dihydroxybenzoate to produce catechol and CO₂.
• The enzyme protocatechuate 3,4-dioxygenase uses 3,4-dihydroxybenzoate and O₂ to produce 3-carboxy-cis,cis-muconate.

See also

• Ethyl protocatechuate

Cited sources

• Book: Haynes. Haynes, William M. . 2016. . 97th . . 9781498754293.

Notes and References

1. Lin . H.-H. . Chen . J.-H. . Huang . C.-C. . Wang . C.-J. . Apoptotic effect of 3,4-dihydroxybenzoic acid on human gastric carcinoma cells involving JNK/p38 MAPK signaling activation . International Journal of Cancer . 120 . 11 . 2306–2316 . June 2007 . 17304508 . 10.1002/ijc.22571 . free .
2. Liu . C.-L. . Wang . J.-M. . Chu . C.-Y. . In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity . Food and Chemical Toxicology . 40 . 635–41 . 2002 . 11955669 . Cheng . M.-T. . Tseng . T.-H. . 5 . 10.1016/s0278-6915(02)00002-9.
3. Babich . H. . Sedletcaia . A. . Kenigsberg . B. . In vitro cytotoxicity of protocatechuic acid to cultured human cells from oral tissue: involvement in oxidative stress . Pharmacology & Toxicology . 91 . 5 . 245–253 . November 2002 . 12570031 . 10.1034/j.1600-0773.2002.910505.x . free .
4. Nakamura . Y. . Torikai . K. . Ohto . Y. . Murakami . A. . Tanaka . T. . Ohigashi . H. . A simple phenolic antioxidant protocatechuic acid enhances tumor promotion and oxidative stress in female ICR mouse skin: dose- and timing-dependent enhancement and involvement of bioactivation by tyrosinase . Carcinogenesis . 21 . 10 . 1899–1907 . October 2000 . 11023549 . 10.1093/carcin/21.10.1899. free .
5. Guan . S. . Ge . D. . Liu . T. Q. . Ma . X.-H. . Cui . Z.-F. . March 2009 . Protocatechuic acid promotes cell proliferation and reduces basal apoptosis in cultured neural stem cells. Toxicology in Vitro. 23. 2. 201–208 . 19095056 . 10.1016/j.tiv.2008.11.008.
6. Anter . J. . Romero Jiménez . M. . Fernández Bedmar . Z. . Villatoro Pulido . M. . Analla . M. . Alonso Moraga . A. . Muñoz Serrano . A. . Antigenotoxicity, cytotoxicity, and apoptosis induction by apigenin, bisabolol, and protocatechuic acid . Journal of Medicinal Food . March 2011 . 14 . 3 . 276–283. 10.1089/jmf.2010.0139 . 21182433 .
7. Hassan . S. T. S. . Švajdlenka . E. . Berchová-Bímová . K. . Hibiscus sabdariffa L. and its bioactive constituents exhibit antiviral activity against HSV-2 and anti-enzymatic properties against urease by an ESI–MS based assay . Molecules . April 2017 . 22 . 5 . 722. 10.3390/molecules22050722 . 28468298 . 6154344 . free .
8. Hassan . S. T. S. . Švajdlenka . E. . Biological evaluation and molecular docking of protocatechuic acid from Hibiscus sabdariffa L. as a potent urease inhibitor by an ESI–MS based method. Molecules. October 2017 . 22 . 10 . 1696. 10.3390/molecules22101696 . 29019930 . 6151788 . free .
9. Antibacterial phenolics from Boswellia dalzielii . Alemika . T. E. . Onawunmi . G. O. . Olugbade . T. O. . Nigerian Journal of Natural Products and Medicines . 2006 . 10 . 108–110 . https://web.archive.org/web/20130730080304/http://dspace.unijos.edu.ng/handle/10485/1174 . dead . 2013-07-30 . 2013-07-30 .
10. Mallavadhani . U. V. . Mahapatra . A. . A new aurone and two rare metabolites from the leaves of Diospyros melanoxylon . Natural Product Research . 2005 . 19 . 91–97. 10.1080/14786410410001704705 . 15700652 . 35200920 .
11. Hackman . R. H. . Pryor . M. G. . Todd . A. R. . The occurrence of phenolic substances in arthropods . The Biochemical Journal . 43 . 3 . 474–477 . 1948 . 16748434 . 1274717 . 10.1042/bj0430474.
12. Journal of Agricultural and Food Chemistry . June 2008 . 56 . 12 . 4631–4636 . Chemical composition, antioxidant properties, and thermal stability of a phytochemical enriched oil from Açaí (Euterpe oleracea Mart.) . 18522407. 10.1021/jf800161u . Pacheco Palencia . L. A. . Mertens-Talcott . S . Talcott . S. T. .
13. Web site: Chemical Query . 2011-09-25 . https://web.archive.org/web/20130616093128/http://www.ars-grin.gov/cgi-bin/duke/highchem.pl . 2013-06-16 . dead .
14. Delsignore . A . Romeo. . F. . Giaccio . M. . Content of phenolic substances in basidiomycetes . Mycological Research . 101 . 552–556 . 1997 . 10.1017/S0953756296003206 . 5.
15. 10.1248/bpb.31.1968 . Lee . Y.-S. . Kang . Y. H. . Jung . J. Y. . etal . Protein glycation inhibitors from the fruiting body of Phellinus linteus . Biological & Pharmaceutical Bulletin . 31 . 10 . 1968–72 . October 2008 . 18827365 . free .
16. Li. Xican. Wang. Xiaozhen. Chen. Dongfeng. Chen. Shuzhi. 2011-07-31. Antioxidant Activity and Mechanism of Protocatechuic Acid in vitro. Functional Foods in Health and Disease. 1. 7. 232. 10.31989/ffhd.v1i7.127. 2160-3855. free.
17. Pietta . P. G. . Simonetti . P. . Gardana . C. . Brusamolino . A. . Morazzoni . P. . Bombardelli . E. . 1998 . Catechin metabolites after intake of green tea infusions . BioFactors . 8 . 1–2. 111–118 . 10.1002/biof.5520080119 . 9699018. 37684286 .