3,4-Dihydroxybenzoic acid

Appl Biochem Biotechnol. 2014 Mar;172(5):2582-92.

Protective effect of 3,4-dihydroxybenzoic acid isolated from Cladophora wrightiana Harvey against ultraviolet B radiation-induced cell damage in human HaCaT keratinocytes.[Pubmed: 24414942]

The aim of the present study was to elucidate the protective properties of 3,4-Dihydroxybenzoic acid (DBA) isolated from Cladophora wrightiana Harvey (a green alga) against ultraviolet B (UVB)-induced damage to human HaCaT keratinocytes.
METHODS AND RESULTS:
3,4-Dihydroxybenzoic acid exhibited scavenging actions against the 1,1-diphenyl-2-picrylhydrazyl radical, the superoxide anion, and the hydroxyl radical. Furthermore, 3,4-Dihydroxybenzoic acid decreased the levels of intracellular reactive oxygen species generated by hydrogen peroxide or UVB treatment of the cells. 3,4-Dihydroxybenzoic acid also decreased the UVB-augmented levels of phospho-histone H2A.X and the extent of comet tail formation, which are both indications of DNA damage.
CONCLUSIONS:
Taken together, these results demonstrate that 3,4-Dihydroxybenzoic acid isolated from a green alga protects human keratinocytes against UVB-induced oxidative stress and apoptosis.

Microb Pathog. 2013 Jun-Jul;59-60:52-9.

Nematicidal activity of 3,4-dihydroxybenzoic acid purified from Terminalia nigrovenulosa bark against Meloidogyne incognita.[Pubmed: 23603737]

In this study, the 3,4-Dihydroxybenzoic acid (3,4-DHBA) from Terminalia nigrovenulosa bark (TNB) was purified and its in vitro nematicidal activity was investigated against Meloidogyne incognita.
METHODS AND RESULTS:
The purification of 3,4-Dihydroxybenzoic acid used a silica gel column and Sephadex LH-20 chromatography combined with thin-layer chromatography and high performance liquid chromatography. Structural identification of the 3,4-Dihydroxybenzoic acid was conducted using (1)H nuclear magnetic resonance (NMR), (13)C NMR, and liquid chromatography time-of-flight mass spectrometry. Nematicidal activity bioassays revealed that 3,4-Dihydroxybenzoic acid treatment resulted in 33.3, 47.5, 72.5 and 94.2% J2 mortality at 0.125, 0.25, 0.5 and 1.0 mg/ml, respectively after 12 h incubation. J2 mortality was increased significantly (P < 0.0001) with increasing incubation time in the range of 54.2-94.2% from 3 to 9 h after incubation with 3,4-Dihydroxybenzoic acid (1.0 mg/ml), but with no significant difference observed where the incubation time was increased from 9 to 12 h. The 3,4-Dihydroxybenzoic acid treatment resulted in 33.3, 65.0, 76.7 and 85.0% hatch inhibition at 0.125, 0.25, 0.5 and 1.0 mg/ml, respectively, 3 days after incubation. Changes in the shape of the eggs were determined after incubation for 1 day with a 3,4-Dihydroxybenzoic acid concentration of 1.0 mg/ml.

Indonesian Journal of Chemistry, 2012, 12(3):273-8.

3,4-dihydroxybenzoic acid and 3,4-dihydroxybenzaldehyde from the fern Trichomanes chinense L.; isolation, antimicrobial and antioxidant properties.[Reference: WebLink]

3,4-Dihydroxybenzoic acid (1) and 3,4-dihydroxybenzaldehyde (2) have been isolated from ethyl acetate fraction of methanolic fractions of leaves, stems and roots of the fern Trichomanes chinense L. (Hymenophyllaceae).
METHODS AND RESULTS:
These two compounds also showed significant antioxidant using DPPH and antimicrobial activities using the disc diffusion assay.

Metab Brain Dis . 2017 Apr;32(2):401-413.

Attenuation of acute restraint stress-induced depressive like behavior and hippocampal alterations with protocatechuic acid treatment in mice[Pubmed: 27785705]

Abstract Protocatechuic acid ethyl ester (PCA), a phenolic compound, exhibits neuroprotective effects through improving endogenous antioxidant enzymatic and nonezymatic system. Based on the role of oxidative stress in modulating depressive disorders and the relationship between neuroprotective and antioxidant potential of PCA, we studied if its antidepressant like effect is associated by modulation of cerebral cortex and hippocampal antioxidant alterations. Acute restraint stress (ARS) is known to induce depressive like behavior by neuronal oxidative damage in mice. Swiss albino mice subjected to ARS exhibited an increased immobility time in forced swim test, elevated serum corticosterone and produced oxidative stress dependent alterations in cerebral cortex and hippocampus mainly increased thiobarbituric acid reactive substances and reduced catalase (CAT), superoxide dismutase (SOD) activity. Treatment with PCA was able to prevent stress induced immobility time in forced swim test without altering locomotor activity in mice. Further, PCA treatment attenuated the elevation of serum corticosterone, lipid peroxidation and restored enzymatic antioxidants in cerebral cortex and hippocampus in ARS mice. Altogether, the experimental findings demonstrate the notion that PCA exhibit antidepressant like activity might be related, at least in part, to its capability of modulating antioxidant defense system and oxidative damage induced by ARS in cerebral cortex and hippocampus in mice and thus maintain the pro-/anti-oxidative homeostasis. Keywords: Acute restraint stress; Depressive like-behavior; Hippocampal antioxidants; Protocatechuic acid ethyl ester; Serum corticosterone.

J Agric Food Chem . 2016 Oct 19;64(41):7722-7732.

Protocatechuic Acid: Inhibition of Fibril Formation, Destabilization of Preformed Fibrils of Amyloid-β and α-Synuclein, and Neuroprotection[Pubmed: 27686873]

Abstract Protocatechuic acid (PCA) is the major metabolite of the anthocyanin known as cyanidin 3-glucoside. It is found in plasma and tissues, such as the brain, heart, liver, and kidneys, following consumption of a rich source of this flavonoid. The abnormal pathological assembly of amyloid-β (Aβ) and α-synuclein (αS) is an underlying mechanism involved in the formation of amyloid plaques and Lewy bodies in the brain, which are responsible for neuropathology symptoms in Alzheimer's (AD) and Parkinson's diseases (PD), respectively. This research was performed to evaluate the protective effects of PCA, by establishing its potential role in inhibiting aggregation and fibril destabilization of Aβ and αS proteins. It has been found that PCA inhibits the aggregation of Aβ and αS and destabilizes their preformed fibrils. These results were confirmed by TEM images, electrophoresis, and immunoblotting experiments. Furthermore, PCA prevents the death of PC12 cells triggered by Aβ- and αS-induced toxicity.

Biomed Pharmacother . 2016 Oct;83:559-568.

Alterations of Na +/K +-ATPase, cholinergic and antioxidant enzymes activity by protocatechuic acid in cadmium-induced neurotoxicity and oxidative stress in Wistar rats[Pubmed: 27454871]

Abstract Background: This study assessed the possible protective mechanisms of protocatechuic acid (PCA) against cadmium (Cd)-induced oxidative stress and neurotoxicity in rats. Methods: Male wistar strain rats weighing between 150-160g were purchased and acclimatized for two weeks. The rats were divided into seven groups of seven each; NC group received normal saline, CAD group received 6mg/kg of Cd-solution, CAD+PSG group received Cd-solution and prostigmine (5mg/kg), CAD+PCA-10 and CAD+PCA-20 groups received Cd-solution and PCA (10mg/kg and 20mg/kg) respectively, PCA-10 and PCA-20 groups received 10mg/kg and 20mg/kg PCA each. Animals were administered normal saline, Cd and PCA daily by oral gavage for 21days. After which the animals were sacrificed, the brain excised, homogenized and centrifuged. The activities of enzymes (Na+/K+-ATPase, cholinesterases, catalase, glutathione peroxidase, superoxide dismutase) and levels of oxidative stress markers (lipid peroxidation and reduced glutathione) linked to neurodegeneration were subsequently assessed. Results: Significant (p<0.05) alterations in the enzyme activities and levels of oxidative stress markers were observed in CAD group when compared to the NC group. However, the activities of the enzymes were reversed in CAD+PSG and CAD+PCA groups. Conclusions: PCA may protect against cadmium-induced neurotoxicity by altering the activities of Na+/K+-ATPase, acetylcholinesterase, butyrylcholinesterase and endogenous antioxidant enzymes. Keywords: Antioxidant; Cadmium; Cholinesterases; Enzymes; Na(+)/K(+) ATPase; Protocatechuic acid.

Int J Cancer. 2007 Jun 1;120(11):2306-16.

Apoptotic effect of 3,4-dihydroxybenzoic acid on human gastric carcinoma cells involving JNK/p38 MAPK signaling activation.[Pubmed: 17304508 ]

3,4-Dihydroxybenzoic acid (protocatechuic acid, PCA) is discussed to represent antioxidative food components in a human diet rich in fruits and vegetables, and has been shown to prevent carcinogenesis or antitumor growth in vivo. However, the molecular mechanisms involved in chemopreventive activity of PCA are poorly understood.
METHODS AND RESULTS:
In this study, investigations were conducted to examine the detailed signaling pathway involved in PCA-induced apoptosis in human gastric adenocarcinoma (AGS) cells. The data from cell viability assay showed that PCA exhibited the antiproliferation effect on AGS cells in a time- and dose-dependent manner. The occurrence of apoptosis induced by PCA was confirmed by morphological and biochemical features, including apoptotic bodies formation and an increase in the distribution of hypodiploid phase. Molecular data showed the effect of PCA in AGS cells might be mediated via sustained phosphorylation and activation of JNK and p38 mitogen-activating protein kinases (MAPK), but not ERK. Treatment with pharmacological inhibitors or transfection with the mutant p38 or/and JNK expression vector reduced PCA-mediated apoptosis and the JNK/p38 MAPK-related proteins phosphorylation and expression, including ATF-2, c-Jun, FasL, Fas, p53 and Bax. Preincubation with Nok-1 monoclonal antibody, which is inhibitory to Fas signaling, interfered with PCA-induced cleavage of procaspase and sensitization to anti-APO-induced apoptosis.
CONCLUSIONS:
These results suggest the possible involvement of multiple signaling pathways from the MAPK to the subsequent mitochondria- and/or Fas-mediated caspase activation are potential requirements for PCA-induced AGS apoptosis. Further, PCA effectively induced JNK/p38 activation in PCA-response cell lines. Taken together, our data present the first evidence of PCA as an apoptosis inducer in AGS cells, even in tumor cells of digestive organs, and provide a new mechanism for its anticancer activity.

Int J Oncol. 2003 Jul;23(1):159-63.

Protection against Adriamycin cytotoxicity and inhibition of DNA topoisomerase II activity by 3,4-dihydroxybenzoic acid.[Pubmed: 12792789]

The mechanism of Adriamycin (ADR) induced cytotoxicity is not completely understood. While a variety of mechanisms have been proposed, the production of free radicals by redox cycling of the semiquinone has been implicated in cytotoxicity, specifically for cardiotoxicity.
METHODS AND RESULTS:
To determine whether a scavenger of free radicals would modify the cytotoxicity of ADR, the benzoic acid derivative 3,4-Dihydroxybenzoic acid (DHB) was investigated for its ability to protect against ADR-induced cytotoxicity and DNA double strand breaks in Chinese hamster V79 cells. V79 cells were treated with ADR, or its non-redox cycling analog iminodaunomycin, in the presence or absence of DHB. DHB provided significant protection (dose-modifying factor greater than 2.5 for ADR, and nearly 2 for iminodaunomycin) and also caused a dose-dependent decrease in DNA double strand breaks as measured by pulsed field gel electrophoresis. Assays of topoisomerase II activity showed that DHB inhibited topoisomerase II in a concentration-dependent manner, but did not inhibit topoisomerase I. Another non-toxic topoisomerase II inhibitor, the radioprotector WR-1065, also protected against ADR-induced cytotoxicity.
CONCLUSIONS:
These data identify DHB as a non-toxic inhibitor of DNA topoisomerase II and suggest that much of the cytotoxicity of ADR in actively growing V79 cells is due to mechanisms other than redox cycling by the semiquinone.

Neurosci Lett. 2007 Jun 13;420(2):184-8.

3,4-dihydroxybenzoic acid from Smilacis chinae rhizome protects amyloid beta protein (25-35)-induced neurotoxicity in cultured rat cortical neurons.[Pubmed: 17531386 ]

The neuroprotective effect of 3,4-Dihydroxybenzoic acid (3,4-DHBA) isolated from Smilacis chinae rhizome against Abeta (25-35)-induced neurotoxicity on cultured rat cortical neurons was found in this study.
METHODS AND RESULTS:
The protective effect of 3,4-DHBA against Abeta (25-35)-induced neuronal cell death was investigated by measuring cell viability via a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. 3,4-DHBA (1 and 10 microM) concentration-dependently inhibited 10 microM Abeta (25-35)-induced neuronal apoptotic death. 3,4-DHBA (1 and 10 microM) inhibited 10 microM Abeta (25-35)-induced elevation of cytosolic Ca(2+) concentration ([Ca(2+)](c)), which was measured by a fluorescent dye, Fluo-4 AM. 3,4-DHBA also inhibited glutamate release into medium, reactive oxygen species (ROS) generation, and caspase-3 activation, which were induced by 10 microM Abeta (25-35).
CONCLUSIONS:
These results suggest that 3,4-DHBA prevents Abeta (25-35)-induced neuronal cell damage by interfering with the increase of [Ca(2+)](c), and then by inhibiting glutamate release, generation of ROS and caspase-3 activity.