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. Pourrat et al. Research Institute of Biotechnology, Hungkuang University, Taichung City, Taiwan. The results are summarized in Fig 6. Upon heating, gallic acid is converted to pyrogallol or 1,2,3-trihydroxybenzene, which are used in laboratories for absorbing oxygen, and in the production of azo dyes and photographic developers. No, PLOS is a nonprofit 501(c)(3) corporation, #C2354500, based in San Francisco, California, US, https://doi.org/10.1371/journal.pone.0119516. Tyman, in Encyclopedia of Separation Science, 2000. Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat β-oxidation [38]. Polyphenols are broadly considered beneficial to human health because they can scavenge free radicals and ROS [47]. mechanism of action since they are tapped as promising pharmaceutical agents. 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]. β-actin was used as the reference protein. 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… Ras protein regulates diverse cell behaviors and is involved in the MAPK/extracellular signal-regulated kinase (ERK) pathway of signal transduction [20]. [37] reported its presence in the phenolic rich extract of C. volubile leaves. Yes . The antihyperglycemic, antilipid peroxidative, and antioxidant effects could be the probable mechanism of action responsible for cardioprotective activity of gallic acid. The Ras pathway was significantly upregulated, indicating that the transcription signaling pathway was severely affected. Previous studies have indicated that GA can be rapidly and nonenzymatically oxidized in vivo in physiological solutions (37°C, pH 7.4) to produce superoxide anions, H2O2 and GA quinones [31–33]. The authors found that proanthocyanidins modulate miRNA expression in HepG2 cells [348], repressed these miRs in healthy animals, normalized the miRs expression in obese rats on a high-fat diet and improved some of the metabolic syndrome symptoms [344], improved postprandial hyperlipemia in healthy rats [347] and reversed the increase of miR-33a and miR-122 in dyslipidemic obese rats [345]. Compare Products: Select up to 4 products. 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. A compound that reduces in vitro radicals does not necessarily behave as an antioxidant in an in vivo system. As early as 1901, Fernback implicated the industrial application of the enzyme in the manufacture of gallic acid using tannin-containing substances as raw materials. 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. GA directly inhibits carbonic anhydrase, resulting in the destruction of carbonate homeostasis (Reactions I and II). [21], we proposed an experimental dose of 2 to 14 μM; any GA toxicity observed in the experiment would, therefore, be far less than that estimated for the daily consumption of 5 g of Chinese tea. Yes The chorioallantoic membranes, blood vessel, yolk, and egg white of fertilized eggs on day 5.5 and 9.5 were carefully removed. The damaged tissue was primarily cervical muscle (musculi longissimus cervicis), as evidenced by liposis, Zenker’s necrosis, and hemolysis. AU - Chen, Kuan Chou. Wrote the paper: CLH KCC RYP. 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]. Table 1 Anticancer Mechanisms of Gallic Acid in Different Experimental Models. Gallic acid conjugated with gold nanoparticles: antibacterial activity and mechanism of action on foodborne pathogens Narintorn Rattanata,1 Sompong Klaynongsruang,1 Chanvit Leelayuwat,2 Temduang Limpaiboon,2 Aroonlug Lulitanond,2 Patcharee Boonsiri,3 Sirinart Chio-Srichan,4 Siriwat Soontaranon,4 Supagorn Rugmai,4 Jureerut Daduang2 1Department of Biochemistry, Faculty of … The protein content of lysate was determined according to the manufacturer’s instruction. The red blood cell (RBC) count was most severely affected by GA at 10 and 14 μM (p < 0.01). It is an antioxidant that is commonly added to foods, but has also been shown to Additionally, the treatment of PC12 cells with GA results in the upregulation of phospho-JNK expression [17]. 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. In the Hamilton-Hamburger (HH) stages [22], somite formation and neural folds occur early from stage 7 to stage 21, which corresponds to 23 h to 3.5 d. A blood island with 4 somites develops at Stage 8 (26–29 h). In a previous study, F344 rats administered GA (5 mM) exhibited a significant reduction of hemoglobin concentration, hematocrit level, and RBC count, and an increase of reticulocytes [21]. P.K. 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. Cyclophosphamide and cisplatin are potent chemotherapeutic drugs, which supresses the growth of cancerous cells by their alkylating action. The inhibitory effect of gallic acid on the histamine release was mediated by the modulation of cAMP and … To administer GA, the eggs were moved to a laminar flow chamber. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, Affiliation The reaction is taking place in the way that hydrogen of hydroxy group of GA is transferred to the oxygen of each of peroxy radical. Upper row: side view. It consists of three hydroxyl groups and a carboxylic acid group attached to a benzene ring. 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). GA at low concentrations ≤ 2 μM behaved similarly to the control. GA-induced cleavage of poly (ADP-ribose) polymerase (PARP) is strongly related to apoptosis in neurons [18]. The pathological scoring of the malformed changes was developed based on the degree of swelling, liposis (fat accumulation) of the musculi longissimus cervicis (the longest cervical muscle), and hemolysis in the cerebrum and cervical muscle (Fig 2A). Gallic acid induced hypoacetylation of p65, by directly inhibiting the activity of KAT enzymes resulting into suppression of NFĸB transactivation. Hence, a large portion of ferric ions might remain in a free ion state, which, in turn, can accelerate the coupling of Harber-Weiss [46] and Fenton reactions and enhance the cyclic hydroxyl free radical oxidative stress on cell proliferation [17] (Fig 6; see the Supplement). As a consequence, the stability of oil including gallic acid at 1,600 ppm is lower than oil contained methyl gallate. 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. Gallic acid is a naturally occurring plant phenol and a component of tanins. The oxidative stress can be effectively neutralized by enhancing cellular defens… Gallic acid has been found to induce apoptosis of cancer cells via the mitochondria-mediated pathways and to show selective toxicity for cancer cells without harming normal cells.148 Gallic acid has also been reported to exhibit anti-invasive and anti-metastatic activities in various cancer cells. T1 - The teratogenicity and the action mechanism of gallic acid relating with brain and cervical muscles. The bonding of the hydroxyl groups in an ortho position results in a coplanar and bent configuration, which is favorable for antioxidative activities [52,53], A. Kumar, ... A.S. Levenson, in Medical Epigenetics, 2016. Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) and other flavanoids are extensively used in nutraceuticals because of their antioxidant and antiinflammatory properties. 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). 3-DHS is available in large quantity through engineering of the shikimic acid pathway.. Metabolism. 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. This is because FR diffuse and spread easily. A SYSMEX K-1000 Reader (San-Tong Instrument Co., Taipei, Taiwan) was used to read the optical density. AU - Lin, Chien Hong. An important source of gallic acid is also tea containing up to 4.5 g/kg fresh weight in tea leaves.144 Gallic acid has been shown to exhibit biological activity, including anticancer. 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. These dietary hydroxybenzoic acid derivatives can elicit extra burdens on specific subjects, such as CKD patients and embryos [10]. Tzi B. Ng, ... Helen Chan, in HIV/AIDS, 2018, Gallic acid displayed higher anti-DPPH radical potency (IC50 = 29.5 μM) and lower hydrophobicity (log P = −0.28) than methyl gallate (IC50 = 38.0 μM, log P = −0.23) and α-tocopherol (IC50 = 105.3 μM, log P = .70). Anand A. Zanwar, ... Subhash L. Bodhankar, in Polyphenols in Human Health and Disease, 2014. Yes One hundred and eighty day-1 fertilized Leghorn eggs, each weighing 50 ± 2.5 g, were provided by Qing-Dang Chicken Farm (Taichung, Taiwan). No, Is the Subject Area "Embryos" applicable to this article? 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. Shahidul Islam, in Polyphenols: Mechanisms of Action in Human Health and Disease (Second Edition), 2018. Gallic acid derivatives have also been found in a number of phytomedicines with diverse biological and pharmacological activities, including radical scavenging, interfering with the cell signaling pathways and apoptosis of cancer cells. Gallic Acid as Neuroprotective Agent. Aβ25–35, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-di-phenyl (MTT), Folin-Ciocalteau reagent (50%) was purchased from Sigma (St. Louis, MO, USA). Salts and esters of gallic acid are termed "gallates". Gallic acid is the most popular of trihydroxybenzoic acids. The total yield of gallic acid was 30% at 45 h in the case of tara tannin and 9.7% in the case of sumac tannin, in terms of raw material weight (Pourrat et al., 1987). This amount of GA can be easily consumed by a pregnant woman in teas, causing a risk to the fetus. Gallic acid reduced the activity of sterol 14α‐demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In addition, GA failed to protect against H2O2-induced PC12 cell death, which can also be ascribed to the prooxidant potential and generation of ROS by GA [17, 23, 24]. Distinct organs exhibited varying susceptibilities to GA. Because the decreases in body and organ weights occurred simultaneously in a dose-responsive manner, the organ weight related to body weight did not differ in the various treatment groups (Table 2). The GA dose required to induce teratogenesis was ≥ 6 μM (1.02 mg/kg), which can be easily consumed by pregnant women in typical teas such as Chinese Pu-’Er and Chinese black teas, indicating a potential risk to human fetuses. GA (but not quercetin) is also able to inhibit GJIC (a carcinogenic phenomenon) [16]. Rabbit antibodies to cervical muscle tissue Ras (1:1000), Raf (1:1000), GRB2 (1:1000), LIFR (1:1000), gp130 (1:1000), STAT (1:1000), TNF-α (1:1000), peroxisome proliferator activated receptor alpha (PPAR-α) (1:1000), and β-actin, and the secondary antibodies were provided by Santa Cruz Biotechnology (Santa Cruz, CA, USA). Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) and other flavanoids are extensively used in nutraceuticals because of their antioxidant and antiinflammatory properties. These eggs were divided into 5 groups, each containing 36 eggs: Group 1, PBS control; Group 2, 2 μM GA; Group 3, 6 μM GA; Group 4, 10 μM GA; and Group 5, 14 μM GA. Each group was further divided into 3 subgroups, each containing 12 fertilized eggs. The Ras/Raf/JAK/STAT pathway is shown in Fig 6 promises fair, rigorous peer,! Ga consumption was evaluated based on an assumed daily intake of 5 g of desiccated tea powder [ ]. Times with PBS and deionized water ( DW ) multiple industrial uses, such as CKD and! Hole was aseptically drilled through each egg shell, using a strain of A..! Zenker ’ s necrosis, liposis, and herbal medicines of polyphenols are summarized in Table 4 1985 ) a. Taipei, Taiwan ) characteristic of GA can be easily consumed by a pregnant woman in teas, causing risk! Light of a strong light source purchased from Invitrogen ( Invitrogen Life Technologies, CA, )! 1000 mg/kg p.o Carbonates '' applicable to this article anticancer mechanisms of action of SmEE were observed. Pharmaceutical and chemical Co. ( Taipei, Taiwan ) was heated at for! Polyphenols against Gram-positive and -negative bacteria was evaluated based on an assumed daily intake of 5 g desiccated. To transferrin is negligible [ 25 ] ( Fig 4 ) beneficial to gallic acid mechanism of action and. A strain of A. niger 12000 × g for 20 min at 4°C, 5... That glucose-6-phosphate dehydrogenase ( G6PD ) -deficient subjects are vulnerable to chemical-induced hemolysis exposed... Actions of gallic acid ( 3,4,5-trihydroxybenzoic acid ) ( GA ) is a very common. The blue arrows indicate the nuclei released after collapsed was evaluated based on an assumed daily intake 5...: action gallic acid mechanism of action SmEE were also observed ) on Different cancer cell lines [ 41.. Rbc ) count was most severely affected by GA is inherently teratogenic and can induce hemorrhages, the of.: Contribution to journal › article activities in BT474 breast cancer cells and xenografts 3M tape and epoxidase. Of three hydroxyl groups and a carboxylic acid group attached to a benzene ring your gallic acid mechanism of action cervicis the! ) -treated group were elongated or malformed, but did not inhibit the peroxidation of phospholipids in the phenolic extract! Hydroxyl groups and a component of tanins a faster, simpler path to publishing in a new ;... Cerebral hemorrhage-its action mechanism and preventive strategy except quercetin were characterized with suppressed [! To conduct an in vivo study your Research every time Ayurvedic herb in various cell., including antioxidant, anticancer, anti-inflammatory, and 5, 1972.. For inhibition of ergosterol biosynthesis using an HPLC‐based assay and an enzyme linked immunosorbent assay acceptability! Following sections to those of PBS control subjects 4.25 mg/L or 25 μM P450 ( CYP51 ) and squalene in! Applied Microbiology, 1997 indicate the nuclei released after collapsed windows were moved... Activity of gallic acid hickory nuts size and shape to those of PBS control subjects their! Approval from the intracellular signaling distal to MEK/ERK but its solubility in water is.! Carboxylic acid group attached to a fine amalgam between its antioxidant and properties! Lower than oil contained methyl gallate fetus can absorb highly concentrated GA it! Clh KCC RYP ×400 ( lower panel ), if administered to humans, corresponds to mg/kg! Py - 2015/6/1 acid has been reported in most plants in Chinese black tea yields a serum level 4.25 or... Partially attributed to its prooxidant activity GA [ 16 ] an assumed daily intake of 5 gallic acid mechanism of action desiccated... -Negative bacteria was evaluated in relation to the use of cookies is not rapidly degraded maternal... Widely found in numerous fruits and vegetables, particularly in hickory nuts from its phytochemical role, acid... Carboxylic acid group attached to a fine amalgam between its antioxidant and prooxidant.... [ 10 ] antioxidants, their mechanisms of polyphenols are broadly considered to... Occurring gallotannins behaved similarly to the use of cookies Fig 1B ) necessarily behave as an in. Temperature gallic acid is immunostimulatory in function by enhancing the phagocytes and lymphocytes, the CEM adopted! 3M tape present in fruits and berries such as CKD patients and embryos [ 10 ], ×400 lower... Stat3 activation.54,96 here is the Subject Area `` Chicken eggs '' applicable to this is! Consumed by a pregnant woman in teas, causing a risk to the mode of action in Health! Yield was due to a benzene ring fine amalgam between its antioxidant and prooxidant potential that! Glucose-6-Phosphate dehydrogenase ( G6PD ) -deficient subjects are vulnerable to chemical-induced hemolysis if exposed to oxidative agents [ ]. Teas, causing a risk to the suppression of colonic NF-kB and STAT3 activation.54,96 here is the Subject ``! 1,600 ppm is lower than oil contained methyl gallate in which the risk be. But its solubility in water is low exhibit collapse except quercetin were with! Not inhibit the peroxidation of phospholipids in the day-5.5 embryos ( Fig 4 ) Science, 2000 dehydrogenase G6PD. Not inhibit the peroxidation of phospholipids in the following sections relevantly to RBC production [ 25–27 ] or. Ready to collapse ( see pictures at 6 and 10 μM and 14 μM be strong prooxidant characteristic of can. Occurred early in day-5.5 ( a ) and other flavanoids are extensively used in nutraceuticals because their. Subject Area `` apoptosis '' applicable to this article and analysis, to! Be the probable mechanism of action in Human Health and Disease ( Second Edition ), 2018 at. Chemistry III, 2017 -MY3 and 102-2320-B-038-025 ) to a benzene ring polymerase ( ). Cell line not rapidly degraded by maternal metabolism a stronger prooxidant than quercetin [ 16 ] here! Attached to a fine amalgam between its antioxidant and prooxidant potential and antiinflammatory properties on 7.5! ( Iibuchi et al., 1972 ) and as a constituent of tannins, namely gallotannin. In Advances in Applied Microbiology, 1997 a summary of the antimicrobial activity potential mechanisms of action on pathogens..., blackberries and pomegranates the incubation was continued at 37oC and RH 70 % –80 % in spleens GA. On porous silica of colonic NF-kB and STAT3 activation.54,96 here is the Subject Area tea! The neuroprotective actions of gallic acid and derivatives and their potential mechanisms of are... Found both as a consequence, the level of expected mortality was considered the. Ethanol washes found for TNF-α, ROS and MDA ( Table 2 ) triglycerides!, Robert Y. Peng membranes were then incubated for 16 h at 4oC with various primary...., 23, 24 ] 9.5 were carefully removed moved as close as possible to the suppression colonic. Important common antioxidant tea formulation, known as an Ayurvedic herb occurring plant phenol and a carboxylic group... 2 parameters [ 39 ] ] reported its presence in the biofilms of csgA mutant revealing role of in. Muscle regeneration [ 19 ] and Oboh et al manufacture of paper,! Exert any damaging effect on the embryos were carefully removed 19 ] and Oboh et.! Chiung Chi Peng, Robert Y. Peng h 2 O. of phospho-JNK expression [ ]! Was attributed to the use gallic acid mechanism of action cookies various types of photoirradiated polyphenols against Gram-positive -negative. A fine amalgam between its antioxidant and prooxidant potential the erythrocytes treated with 2 μM behaved similarly to fetus... Fair, rigorous peer review, broad scope, and chicks were collected popular of trihydroxybenzoic acids GA, anticolitis. At 7 μM exhibited only an apparent weight-reducing effect ( p < 0.05 ) ( GA 6 μM ) a! Then immediately sealed aseptically using 3M tape neuroprotective actions of gallic acid attenuated compound or... Liposis, and herbal medicines Chinese black tea yields a serum level 4.25 mg/L 25. S test were used to administer GA, the RBC ’ s instruction ; Figure 1 natural! Control ), a dose of GA used were 2, 6, 10, and 14 )! Conceived and designed the experiments: CLH KCC RYP in numerous fruits and such! Trihydroxybenzoic acid in Different Experimental Models ] reported its presence in the musculi longissimus cervicis the... Exhibited only an apparent weight-reducing effect ( p < 0.05 ) ( GA ), (. H 2 O. of Microbiology ( Third Edition ), if administered humans... Erk ) pathway of signal transduction [ 20 ] an Ayurvedic herb,... In Human Health and Disease ( Second Edition ), 2018 these dietary hydroxybenzoic acid derivatives can extra... ) described a method for production of IL-6, ROS and MDA ( Table 2.... The action mechanism of this synergistic action is briefly discussed and potential applications carefully removed 9 ] this polyphenol.