https://doi.org/10.1371/journal.pone.0119516.t004. Alzheimer disease (AD), a neurodegenerative disorder, identified by extracellular aggregates of amyloid-beta (Aβ) protein called plaques and intraneuronal aggregates of tau called neurofibrillary tangles. Gallic acid is also used in the enzymatic synthesis of propyl gallate, which is mainly used an an antioxidant in fats and oils, as well as in beverages (Weetal, 1985a). These findings could pave the way for the development of functional compound from gallic acid–rich plants for mitigation of … Considering the use of this species in ethnomedicine, its anti-inflammatory and antioxidant activities, our study investigated the antiulcerogenic activity of the Spondias mombin ethanolic extract (SmEE), isolated gallic acid (GA), and ellagic acid (EA) and in association between gallic acid and ellagic acid. Because GA is widely used in numerous foods and drinks, such as oolong tea, higher risks can be raised by the dietary uptake, particularly in tea beverages. Tannase hydrolyzes tannic acid to glucose and gallic acid (Iibuchi et al., 1972). While examining whether GA is effective in alleviating valproic-acid-induced teratogenesis in a chicken embryo model (CEM), we observed embryo hemorrhage and liposis in the musculi longissimus cervicis. The alive day-1 chicks were euthanized under CO2-anethesia and the liver, pancreas, spleen, and necks of all chicks were excised, rinsed 3 times with PBS, dried using tissues, and weighed. However, as the actual prevalence rate of hemolysis in embryos reached only 5.5–10.5% which was included in the damaging rate (as addressed in the footnote of Table 1), we established a subscoring system based on the degree of edema, liposis, and hemolysis for further clssification of the status (Fig 2B). With this proviso and by the use of the strict linearity range, the values obtained for gallic acid were 98±2.1% of those found by HPLC. Gallic acid induced hypoacetylation of p65, by directly inhibiting the activity of KAT enzymes resulting into suppression of NFĸB transactivation. In terms of pharmaceutical production, gallic acid is used in the synthesis of trimethoprim. We suggest that the regulation of STAT3 signaling pathway via the outstanding bioactivities of gallic acid including antioxidant potential, anti-inflammatory effect, apoptotic action, and antitumor impact may be the probable mechanism by which it can offer its therapeutic action against HCC. Thus far, most cited GA effects have been positive regarding antiteratogenesis [12, 13]; only a few studies have implicated negative effects caused by its prooxidative activity, including damage to aorta vascular smooth muscle cells (VSMCs) [14] and cytotoxic effects on testicular cells [15]. Crude samples from enzymatic solutions were diluted between one- and 100-fold with methanol and filtered through a Minisart NML 0.45 μm filter and gallic acid used at known concentrations as an internal standard. Normal biochemical reactions, increased exposure to the environment, and higher levels of dietary xenobiotics result in the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS).2 ROS and RNS are responsible for the oxidative stress in different pathophysiological conditions.3 Cellular constituents of our body are altered in oxidative stress conditions, resulting in various disease states. [37] reported its presence in the phenolic rich extract of C. volubile leaves. Gallic acid is a trihydroxybenzoic acid in which the hydroxy groups are at positions 3, 4, and 5. The gp130, leukemia inhibitory factor receptor (LIFR), GRB2, Ras, STAT, and PPAR-α were analyzed using immunoassay methods, according to the manufacturers’ instructions. Salts and esters of gallic acid are termed "gallates". All other reagents were purchased from Invitrogen (Invitrogen Life Technologies, CA, USA) unless otherwise stated. Mechanisms of action of antioxidants. From day 9.5 to day 10, primitive chick morphology can be clearly observed, and, during this period, the length of the third toe from the tip to the middle of the metatarsal joint can reach 5.4 ± 0.3 mm; the length of the beak from the anterior angle of the nostril to the tip of the bill can reach 2.5 mm; and the primordium of the comb, the labial groove, and the uropygial gland are all well developed. The red blood cell (RBC) count was most severely affected by GA at 10 and 14 μM (p < 0.01). Yes Be-sides, this work is also focused on the investigation of HAT and SPLET mechanisms for species with one or two deprotonated OH groups that may be the main reaction pathways in water. 133 - N° C - Article : 110985 - Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases - EM consulte GA-induced cleavage of poly (ADP-ribose) polymerase (PARP) is strongly related to apoptosis in neurons [18]. Conceived and designed the experiments: CLH KCC RYP. GA downregulates Bcl-2 in PC12 cells through the combined effects of dietary phenolics and reactive oxygen species (ROS) on oxidative neuronal cell death [18]. In a previous study, F344 rats administered 10 μM GA exhibited significant loss not only in body weight [21] (Table 2), but also in liver weight in a dose-responsive manner, when compared with both PBS controls and subjects administered 2 μM GA. More severe pathological changes were observed in the 14 μM treated subjects, which exhibited severe hemorrhaging and Zenker’s necrosis in the cervical muscles (Fig 3). Following the study of Niho et al. Click through the PLOS taxonomy to find articles in your field. The western blot analysis revealed that the signal proteins gp130, leukemia inhibitory factor receptor (LIFR), growth factor receptor-bound protein 2 (GRB2), Ras, and STAT were all upregulated by GA in a dose-responsive manner (Fig 5B), implicating the signal transduction pathways of Ras/Raf-mediated-growth inhibition and differentiation. Tannic acid is an important gallotannin belonging to the hydrolysable class, while catechin belongs to the non-hydrolysable class.2 Hydrolysable tannins are esters of phenolic acids and a polyol, usually glucose.1,3 The phenolic acids are either gallic acid in gallotannins, or hexahydroxydiphenic acid in ella… J.H.P. Impact of Gallic Acid on Gut Health: Focus on the Gut Microbiome, Immune Response, and Mechanisms of Action Front Immunol . The LIF is a polyfunctional cytokine that affects the differentiation, survival, and proliferation of a wide variety of cells in adults and embryos [43, 44]. Rokem, in Encyclopedia of Microbiology (Third Edition), 2009. Data Availability: All relevant data are within the paper and its Supporting Information files. Gallic acid is a well-known natural antioxidant that is basically a secondary polyphenolic metabolite. The erythrocyte, hemoglobin, eosinophil, lymphocyte, and monocyte counts were severely reduced and PPAR-α was downregulated, whereas the Ras/Raf/JAK/STAT pathway was upregulated. GA dose-responsively generates considerably more H2O2 in plain DMEM media than quercetin does, and GA acts as a stronger prooxidant than quercetin does [16]. 2 Citations (Scopus) Abstract. To determine whether GA is potentially teratogenic and can induce hemorrhages, the CEM was adopted to conduct an in vivo study. In the present study, photoirradiation induced reactive oxygen species formation was investigated for augmentation of the antimicrobial activity of gallic acid. Orthoquinones formed by the loss of 2 electrons from pyrogallol and catechol (2 adjacent phenol groups) moieties can biochemically participate in enzymatic redox cycling reactions, which can produce superoxides and other ROS [50]. In examining the malformation and teratogenicity, GA at 10 μM was observed to be the optimal dose, which elicited the maximum malformation rate and the lowest still birth rate. The suppressing effect of GA on RBC generation can be partially attributed to its prooxidant activity. Y1 - 2015/6/1. As a consequence, the stability of oil including gallic acid at 1,600 ppm is lower than oil contained methyl gallate. GA (but not quercetin) inhibits gap-junction intercellular communication (GJIC; a carcinogenic phenomenon), which is only partially reduced by catalase [16]. The targeted tissue was typically that of the musculi longissimus cervicis (the longest cervical muscle). Typically, the organ most prominently damaged by GA was the cervix; therefore, HE staining was selectively conducted on the cervical muscles (musculus longissimus cervicis). The inhibition of carbonic anhydrase might disturb carbonate homeostasis and destroy the carbonate bridging ligand of the transferrin-carbonate-ferric ion complex (Kd = 10–22 M) [26, 27]. L.R. The incubation was continued at 37oC and RH 70%–80%. Contributed reagents/materials/analysis tools: KCC CCP. (B) The Ras/Raf-mediated growth inhibition and differentiation induced by gallic acid. In conclusion, this study demonstrates that the hepatocarcinogenic effect of N-nitrosodiethylamine can be abrogated by gallic acid supplementation owing to its affinity to regulate signal transducer and … One of the ways used for obtaining gallic acid (3,4,5-trihydroxybenzoic acid), an important intermediate in synthesis for the pharmaceutical and food industries, is by the acid hydrolysis of natural gallotannins, for example from gall nuts, tara pods or sumac leaves. Graduate Institute of Biotechnology, Changhua University of Education, Changhua, Taiwan, * E-mail: kc.chen416@msa.hinet.net (KCC); misspeng@ms2.hinet.net (CCP), Affiliations [9], a daily consumption of 5 g of Chinese Pu-’Er tea contains 74.5 mg of GA (or 1.24 mg/kg), corresponding to a serum level of 18.6 mg/L (109.3 μM), based on an assumed total blood volume of 4 L for a pregnant woman. Introduction. Gallic acid is mainly used as a synthetic intermediate for the production of pyrogallol and gallic acid esters used in the food and pharmaceutical industries (Deschamps and Lebeault, 1984). The deprotonation of gallic acid, in aqueous solution, is predicted to increase the protective action of this compound against oxidative stress. Gallic acid and its derivatives are present in nearly every part of the plant, such as bark, wood, leaf, fruit, root, and seed.95 Gallic acid has been shown to effectively suppress DSS-induced colitis in mice. https://doi.org/10.1371/journal.pone.0119516.t003. GA at doses ≥ 1.02 mg/kg of body weight potentially causes characteristic cerebral hemolysis and liposis in the musculi longissimus cervicis. GA at 2 μM did not exert any damaging effect on the embryos (Fig 1A and 1B, Table 1). Gallic acid has been detected in trace amounts in brains (mouse model of Alzheimer’s disease) after repeated administration of grape seed polyphenolic extract for 10 days (intragastric gavage of 50, 100 and 150 mg/kg b.w.) Both LIFR and gp130 include components of the receptors for the majority of hematopoietic cytokines [45], further implicating the alternate role of GA in inducing embryonic hemolysis (Fig 1). was found to be non-toxic, indicating the safety of gallic acid. No, Is the Subject Area "Chicken eggs" applicable to this article? [40]. Deschamps and Lebeault (1984) reported the production of gallic acid from tara tannin by using Klebsiella pneumoniae and Corynebacterium spp., where the yield of gallic acid was 55%. 3-Dehydroshikimate is then reduced to shikimic acid by the enzyme shikimate dehydrogenase, which … This compound is a primary constituent of several tannin-bearing plants that produce ellagitannins.151 Ellagic acid has been reported to possess anticarcinogenic activity in several animal models. Scheme 12b demonstrate an alternative mechanism, where the radical-scavenging activity of allicin can be accounted for 2-propenesulfenic acid, which is produced from allicin by Cope elimination. This amount of GA can be easily consumed by a pregnant woman in teas, causing a risk to the fetus. To administer GA, the eggs were moved to a laminar flow chamber. The diverse range of applications of this simple polyphenol is due to a fine amalgam between its antioxidant and prooxidant potential. Phenolic compounds (delphinidin and gallic acid), at concentrations that encompassed the physiologically relevant range (10 nM–100 μM), were prepared in tissue culture medium prior to addition of Tempone-H (10 mM stock, dissolved in ultrapure water) to generate a final concentration of 2 mM. The autocrine-paracrine signaling diverges from the intracellular signaling distal to MEK/ERK. Chiu Lan Hsieh, Chien Hong Lin, Hui Er Wang, Chiung Chi Peng, Robert Y. Peng. A compound that reduces in vitro radicals does not necessarily behave as an antioxidant in an in vivo system. 3-DHS is available in large quantity through engineering of the shikimic acid pathway.. Metabolism. In this study, the mechanism of action of gallic (GA) and ferulic (FA) acids, a hydroxybenzoic acid and a hydroxycinnamic acid, was assessed on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Listeria monocytogenes. The aim of the present study was to elucidate whether gallic acid modulates the inflammatory allergic reaction and to study its possible mechanisms of action. TLC analysis was performed on glass plates (5×20 cm), coated with a 0.25 mm layer of RP-18 F254 (Merck 15683); the glass plates were pre-cleaned with a single development in methanol. The antibacterial action mechanisms of polyphenols are summarized in Table 4. The most important dietary source of phenolic acids in all studied European countries was coffee (58–75%), and the most distributed phenolic acids were caffeoylquinic acids (mainly 5-caffeoylquinic, 4-caffeoylquinic and 3-caffeoylquinic acid), followed by feruloylquinic, gallic, galloylquinic, 4-hydroxyphenylacetic, homovanillic, 3,4-dihydroxyphenylacetic and dihydro-p-coumaric acids . No, Is the Subject Area "Body weight" applicable to this article? The carbonate bridging ligand of the transferrin-carbonate-ferric ion complex has a dissociation coefficient Kd = 10–22 M. When the dissociation coefficient is destroyed, the released ferric ions accelerate the Harber-Weiss reaction [46] to be coupled by the Fenton reaction, cyclically producing large amounts of hydroxyl free radicals, exerting substantial oxidative stress on the proliferating and differentiating cells [17]. (A) Western blotting of the PPAR-α expression. The changes in PPAR-α explained why liposis accompanied hemolysis in the musculi longissimus cervicis when the chicken embryos were treated with GA; GA downregulated the level of PPAR-α in the musculi longissimus cervicis in a dose-responsive manner. AU - Peng, Robert Y. PY - 2015/6/1. In this review, we discuss about the neuroprotective actions of gallic acid and derivatives and their potential mechanisms of action. Moreover, the inhibition of carbonic anhydrase might cause the dissociation of the transferrin-carbonate-ferric ion complex, causing a severe hemolytic response [26, 27]. We conducted this study to determine whether GA is inherently teratogenic and the extent to which the risk can be transferred to fetuses. The levels of IL-6, TNF-α, ROS, and MDA in the cervical muscles of the chicken embryos were determined using ELISA kits, according to the manufacturers’ instructions. The liver weights decreased to 4.0, 3.8, and 3.2 g (p < 0.05) after GA treatment at 3, 5, and 7 μM, respectively (Table 2). Mango polyphenolics including gallic acid and gallotannins inhibited cell and tumor-cytotoxic activities in BT474 breast cancer cells and xenografts. Gallic Acid as Neuroprotective Agent. One hundred and eighty day-1 fertilized Leghorn eggs, each weighing 50 ± 2.5 g, were provided by Qing-Dang Chicken Farm (Taichung, Taiwan). e0119516. The antihyperglycemic, antilipid peroxidative, and antioxidant effects could be the probable mechanism of action responsible for cardioprotective activity of gallic acid. reported that GA kills melanoma cell lines through the Ras/JAK/STAT pathway [20], this signal pathway was also carefully analyzed using a western blot. The embryos were successively rinsed several times with PBS and deionized water (DW). Gallic acid is a naturally occurring plant phenol and a component of tanins. Similarly, 17 mg of GA (or 0.28 mg/kg) in Chinese black tea yields a serum level 4.25 mg/L or 25 μM. Cerebral hemorrhage can be at least partially attributed to the strong prooxidant characteristic of GA [16, 23, 24]. The embryos were then moved as close as possible to the holes by carefully turning the egg in front of a strong light source. Gallic acid was also identified as a versatile scavenger, capable of rapidly deactivating a wide variety of reactive oxygen species (ROS) and reactive nitrogen species (RNS) via electron transfer at physiological pH. Because GA at 2 μM did not exert any detrimental effect, only 6, 10, and 14 μM doses are presented in (B). Cyclophosphamide and cisplatin are potent chemotherapeutic drugs, which supresses the growth of cancerous cells by their alkylating action. GA increases ROS levels, including •O2-, induces GSH depletion, and inhibits the growth of lung cancer and normal cells [34]. here. In an enzymatic procedure hydrolysis of these types of raw material with a fungal tannin acylhydrolase which cleaves depside bonds, the monitoring of a large number of samples by a simple and rapid TLC method was investigated as a potential alternative to HPLC analysis. Heavily reducing species such as pyrogallol (3 adjacent phenol groups) containing (–)-epigallocatechin (EGC) and (–)-epigallocatechingallate (EGCG), typically produces superoxide radicals from molecular oxygen [49]. Data obtained in the same group were analyzed using a Student’s t test and SPSS 10.0 statistical software (SPSS, Chicago, IL, USA). The extracellular pathway mediates its effect through LIF expression and activation of JAK-STAT3. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC‐based assay and an enzyme linked immunosorbent assay. https://doi.org/10.1371/journal.pone.0119516, Academic Editor: Yuan-Soon Ho, Taipei Medical University, TAIWAN, Received: August 30, 2014; Accepted: January 29, 2015; Published: June 1, 2015, Copyright: © 2015 Hsieh et al. The fetus immunoglobulin E ( IgE ) -induced histamine release from mast cells have declared that No competing interests the! 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