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. It is produced commercially from vanillin.
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InChI=1S/C7H6O4/c8-5-2-1-4(7(10)11)3-6(5)9/h1-3,8-9H,(H,10,11) |
YQUVCSBJEUQKSH-UHFFFAOYSA-N |
C(=O)(C1=CC(=C(C=C1)O)O)O |
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Ficus mucuso
(NCBI:txid309328)
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Found in
fruit
(BTO:0000486).
Methanolic extract of air-dried and powdered figs(fruits)
See:
PubMed
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Origanum vulgare
(NCBI:txid39352)
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Found in
aerial part
(BTO:0001658).
95% EtOH extract of dried and powdered aerial parts
See:
PubMed
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Oryza sativa
(NCBI:txid4530)
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See:
PubMed
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Cordyceps sinensis
(NCBI:txid72228)
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Found in
mycelium
(BTO:0001436).
Ethanolic extract of dried mycelia
See:
PubMed
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Alpinia
(NCBI:txid94326)
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See:
PubMed
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Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor
An EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor that interferes with the action of procollagen-proline dioxygenase (EC 1.14.11.2).
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor
An EC 1.1.1.* (oxidoreductase acting on donor CH-OH group, NAD+ or NADP+ acceptor) inhibitor that interferes with the action of shikimate dehydrogenase (EC 1.1.1.25).
human xenobiotic metabolite
Any human metabolite produced by metabolism of a xenobiotic compound in humans.
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
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antineoplastic agent
A substance that inhibits or prevents the proliferation of neoplasms.
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View more via ChEBI Ontology
Outgoing
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3,4-dihydroxybenzoic acid
(CHEBI:36062)
has functional parent
benzoic acid
(CHEBI:30746)
3,4-dihydroxybenzoic acid
(CHEBI:36062)
has role
antineoplastic agent
(CHEBI:35610)
3,4-dihydroxybenzoic acid
(CHEBI:36062)
has role
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor
(CHEBI:77484)
3,4-dihydroxybenzoic acid
(CHEBI:36062)
has role
EC 1.14.11.2 (procollagen-proline dioxygenase) inhibitor
(CHEBI:132365)
3,4-dihydroxybenzoic acid
(CHEBI:36062)
has role
human xenobiotic metabolite
(CHEBI:76967)
3,4-dihydroxybenzoic acid
(CHEBI:36062)
has role
plant metabolite
(CHEBI:76924)
3,4-dihydroxybenzoic acid
(CHEBI:36062)
is a
catechols
(CHEBI:33566)
3,4-dihydroxybenzoic acid
(CHEBI:36062)
is a
dihydroxybenzoic acid
(CHEBI:23778)
3,4-dihydroxybenzoic acid
(CHEBI:36062)
is conjugate acid of
3,4-dihydroxybenzoate
(CHEBI:36241)
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Incoming
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1-(3,4-dihydroxybenzoyl)-β-D-glucopyranose
(CHEBI:136876)
has functional parent
3,4-dihydroxybenzoic acid
(CHEBI:36062)
ethyl 3,4-dihydroxybenzoate
(CHEBI:132364)
has functional parent
3,4-dihydroxybenzoic acid
(CHEBI:36062)
methyl 3,4-dihydroxybenzoate
(CHEBI:132366)
has functional parent
3,4-dihydroxybenzoic acid
(CHEBI:36062)
3,4-dihydroxybenzoate
(CHEBI:36241)
is conjugate base of
3,4-dihydroxybenzoic acid
(CHEBI:36062)
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3,4-dihydroxybenzoic acid
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3,4-Dihydroxybenzoic acid
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KEGG COMPOUND
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4,5-Dihydroxybenzoic acid
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ChemIDplus
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4-Carboxy-1,2-dihydroxybenzene
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ChemIDplus
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Protocatechuic acid
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KEGG COMPOUND
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Protocatechuic acid
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ChemIDplus
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Protocatehuic acid
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ChemIDplus
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1448841
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Reaxys Registry Number
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Reaxys
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99-50-3
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CAS Registry Number
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KEGG COMPOUND
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99-50-3
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CAS Registry Number
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ChemIDplus
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99-50-3
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CAS Registry Number
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NIST Chemistry WebBook
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Roux A, Xu Y, Heilier JF, Olivier MF, Ezan E, Tabet JC, Junot C (2012) Annotation of the human adult urinary metabolome and metabolite identification using ultra high performance liquid chromatography coupled to a linear quadrupole ion trap-Orbitrap mass spectrometer. Analytical chemistry 84, 6429-6437 [PubMed:22770225] [show Abstract] Metabolic profiles of biofluids obtained by atmospheric pressure ionization mass spectrometry-based technologies contain hundreds to thousands of features, most of them remaining unknown or at least not characterized in analytical systems. We report here on the annotation of the human adult urinary metabolome and metabolite identification from electrospray ionization mass spectrometry (ESI-MS)-based metabolomics data sets. Features of biological interest were first of all annotated using the ESI-MS database of the laboratory. They were also grouped, thanks to software tools, and annotated using public databases. Metabolite identification was achieved using two complementary approaches: (i) formal identification by matching chromatographic retention times, mass spectra, and also product ion spectra (if required) of metabolites to be characterized in biological data sets to those of reference compounds and (ii) putative identification from biological data thanks to MS/MS experiments for metabolites not available in our chemical library. By these means, 384 metabolites corresponding to 1484 annotated features (659 in negative ion mode and 825 in positive ion mode) were characterized in human urine samples. Of these metabolites, 192 and 66 were formally and putatively identified, respectively, and 54 are reported in human urine for the first time. These lists of features could be used by other laboratories to annotate their ESI-MS metabolomics data sets. | Wang D, Zou T, Yang Y, Yan X, Ling W (2011) Cyanidin-3-O-β-glucoside with the aid of its metabolite protocatechuic acid, reduces monocyte infiltration in apolipoprotein E-deficient mice. Biochemical pharmacology 82, 713-719 [PubMed:21569764] [show Abstract] Polyphenols, including anthocyanins, from various plant foods are effective in reducing the severity of atherosclerosis in animal and human studies. Due to the poor understanding of the bioavailability of anthocyanins, the potential antiatherogenic mechanisms underlying the action remain largely unknown. Herein, we found that oral gavage of cyanidin-3-O-β-glucoside (Cy-3-G) could be transformed into protocatechuic acid (PCA), and the plasma maximal levels of Cy-3-G were 3.7-fold lower than that of PCA in the apolipoprotein E (ApoE)-deficient mice. Subsequently, we observed that PCA treatment has a higher capacity than Cy-3-G treatment in decreasing CC chemokine receptor 2 (CCR2) expression in the mouse peripheral blood monocytes (PBMs), along with reducing the mouse PBMs chemokine toward CC ligand-2 (CCL2) in a Boyden chamber. Interesting, in the ApoE-deficient mouse model, orally gavaged with Cy-3-G has a higher ability than gavaged with PCA to reduce CCR2 expression in PBMs. PBMs deprived from the Cy-3-G-treated ApoE-deficient mice have a lower ability than those from PCA-treated animals to migrate toward CCL2. Furthermore, as compared with the PCA group, Cy-3-G treatment more efficiently reduced thioglycollate-induced macrophage infiltration into the abdominal cavity. Thus, we suggest that Cy-3-G may reduce the monocyte infiltration in mice via down-regulation of CCR2 expression in monocytes, at least in part, with the aid of its metabolite PCA. These above data imply that the anti-monocyte/macrophage infiltration property of Cy-3-G and its metabolite PCA may be an important antiatherogenic mechanism for anthocyanins. | Lin HH, Chen JH, Chou FP, Wang CJ (2011) Protocatechuic acid inhibits cancer cell metastasis involving the down-regulation of Ras/Akt/NF-κB pathway and MMP-2 production by targeting RhoB activation. British journal of pharmacology 162, 237-254 [PubMed:20840540] [show Abstract]
Background and purposeProtocatechuic acid (PCA) is plentiful in edible fruits and vegetables and is thus one anti-oxidative component of normal human diets. However, the molecular mechanisms involved in the chemopreventive activity of PCA are poorly understood. Here, we investigated the mechanism(s) underlying the anti-metastatic potential of PCA.Experimental approachWe used AGS cells in a wound healing model and Boyden chamber assays in vitro and injection of B16/F10 melanoma cells in mice (metastasis model in vivo) to analyse the effect of PCA on cancer cell invasion and metastasis. The activities and expression of molecular proteins were measured by zymographic assay, real-time RT-PCR and Western blotting.Key resultsPCA inhibited cell migration and invasion at non-cytotoxic concentrations. Decreased expression of matrix metalloproteinase (MMP)-2 and a coincident increase in tissue inhibitor of MMP followed treatment with PCA. The PCA-inhibited MMP-2 activity and expression was accompanied by inactivation of NF-κB. All these effects of PCA could be mediated via the RhoB/ protein kinase Cε (PKCε) and Ras/Akt cascade pathways, as demonstrated by inhibition of PKCε and transfection of PKCε siRNA and ras overexpression vector. Finally, PCA inhibited metastasis of B16/F10 melanoma cells to the liver in mice.Conclusion and implicationsOur data imply that PCA down-regulated the Ras/Akt/NF-κB pathway by targeting RhoB activation, which in turn led to a reduction of MMP-mediated cellular events in cancer cells and provides a new mechanism for the anti-cancer activity of PCA. | Bankeu JJ, Khayala R, Lenta BN, Noungoué DT, Ngouela SA, Mustafa SA, Asaad K, Choudhary MI, Prigge ST, Hasanov R, Nkengfack AE, Tsamo E, Ali MS (2011) Isoflavone dimers and other bioactive constituents from the figs of Ficus mucuso. Journal of natural products 74, 1370-1378 [PubMed:21619045] [show Abstract] Phytochemical investigation of the figs of Ficus mucuso led to the isolation of three new isoflavone dimer derivatives, mucusisoflavones A-C (1-3), together with 16 known compounds. Some of the isolates were tested in vitro for their inhibitory properties toward β-glucuronidase and Plasmodium falciparum enoyl-ACP reductase (PfENR) enzymes. Compound 1 (IC₅₀) 0.68 μM) showed inhibitory activity on β-glucuronidase enzyme, while 3 (IC₅₀) 7.69 μM) exhibited a weak inhibitory activity against P. falciparum enoyl-ACP reductase (PfENR). | Chou TH, Ding HY, Lin RJ, Liang JY, Liang CH (2010) Inhibition of melanogenesis and oxidation by protocatechuic acid from Origanum vulgare (oregano). Journal of natural products 73, 1767-1774 [PubMed:20973550] [show Abstract] Antioxidant and antimelanogenesis activities of protocatechuic acid (1) from Origanum vulgare (oregano) were investigated. The antioxidative capacity of 1 was confirmed from its free-radical-scavenging activities, inhibition of lipid peroxidation, and suppression of reactive oxygen species in H(2)O(2)-induced BNLCL2 cells. The inhibition by 1 of tyrosinase and DOPA oxidase activity and melanin production was possibly related to the down-regulation of melanocortin-1 receptor, microphthalmia-associated transcription factor, tyrosinase, tyrosinase-related proteins-2, and tyrosinase-related proteins-1 expression in α-melanocyte-stimulating hormone-induced B16 cells. After a gel containing 1 was applied to mice, the values of L* slightly increased, and a* and erythema-melanin levels of skin were reduced by comparing the values of untreated control groups, indicating 1 can reduce melanin production. These results suggest that 1 may act as an effective quencher of oxidative attackers with antimelanogenesis properties. | Myllyharju J (2008) Prolyl 4-hydroxylases, key enzymes in the synthesis of collagens and regulation of the response to hypoxia, and their roles as treatment targets. Annals of medicine 40, 402-417 [PubMed:19160570] [show Abstract] Prolyl 4-hydroxylases (P4Hs) have central roles in the synthesis of collagens and the regulation of oxygen homeostasis. The 4-hydroxyproline residues generated by the endoplasmic reticulum (ER) luminal collagen P4Hs (C-P4Hs) are essential for the stability of the collagen triple helix. Vertebrate C-P4Hs are alpha2beta2 tetramers with three isoenzymes differing in their catalytic alpha subunits. Another P4H family, the HIF-P4Hs, hydroxylates specific prolines in the alpha subunit of the hypoxia-inducible transcription factor (HIF), a master regulator of hypoxia-inducible genes, and controls its stability in an oxygen-dependent manner. The HIF-P4Hs are cytoplasmic and nuclear enzymes, likewise with three isoenzymes in vertebrates. A third vertebrate P4H type is an ER transmembrane protein that can act on HIF-alpha but not on collagens. All P4Hs require Fe2+, 2-oxoglutarate, O2, and ascorbate. C-P4Hs are regarded as attractive targets for pharmacological inhibition to control excessive collagen accumulation in fibrotic diseases and severe scarring, while HIF-P4H inhibitors are believed to have beneficial effects in the treatment of diseases such as myocardial infarction, stroke, peripheral vascular disease, diabetes, and severe anemias. Studies with P4H inhibitors in various animal models of fibrosis, anemia, and ischemia and ongoing clinical trials with HIF-P4H inhibitors support this hypothesis by demonstrating efficacy in many applications. | Vitaglione P, Donnarumma G, Napolitano A, Galvano F, Gallo A, Scalfi L, Fogliano V (2007) Protocatechuic acid is the major human metabolite of cyanidin-glucosides. The Journal of nutrition 137, 2043-2048 [PubMed:17709440] [show Abstract] The metabolic fate of dietary anthocyanins (ACN) has not been fully clarified in humans. In all previous studies, the proportion of total ACN absorbed and excreted in urine was <1% intake. This study aimed to elucidate the human metabolism of cyanidin-glucosides (CyG) contained in blood orange juice (BOJ). One liter of BOJ, containing 71 mg CyG, was consumed by 6 healthy, fasting volunteers. Blood, urine, and fecal samples were collected at baseline and at different times up to 24 h after juice consumption. The content of native CyG, glucuronidated/methylated derivatives, and various phenolic acids was determined by HPLC/MS/MS. The serum maximal concentration of cyanidin-3-glucoside (Cy-3-glc) was 1.9 +/- 0.6 nmol/L and that of protocatechuic acid (PCA) was 492 +/- 62 nmol/L at 0.5 h and 2 h after juice consumption, respectively. The calculated total amounts in plasma corresponded for Cy-3-glc to 0.02% and for PCA to 44% of CyG ingested. CyG and glucuronidated/methylated metabolites, but not PCA, were detected in urine. ACN recovered in 24-h urine collections represented approximately 1.2% of the ingested dose. Both CyG (1.90 +/- 0.04 nmol/g) and PCA (277 +/- 0.2 nmol/g) were recovered in 24-h fecal samples. Data explained the metabolic fate of 74% of BOJ ACN. PCA was for the first time, to our knowledge, identified in humans as a CyG metabolite, accounting for almost 73% of ingested CyG. A high concentration of PCA may explain the short-term increased plasma antioxidant activity observed after intake of cyanidin-rich food and it can also contribute to the numerous health benefits attributed to dietary ACN consumption. |
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