Citation: Hsieh CL, Lin C-H, Chen KC, Peng C-C, Peng RY (2015) The Teratogenicity and the Action Mechanism of Gallic Acid Relating with Brain and Cervical Muscles. Among various polyphenols, gallic acid (3,4,5-trihydroxybenzoic acid), a naturally occurring low molecular weight triphenolic compound, has emerged as a strong antioxidant and an efficient apoptosis inducing agent. It might be a potential preventive and therapeutic agent against gastric cancer metastasis.149 Another study in human glioma cells has indicated that gallic acid inhibits cell proliferation and significantly decreases cell viability, invasion and tube formation.150 All these findings suggest that further investigations on the use of gallic acid as a chemopreventive and therapeutic agent are warranted. Ellagic acid is a dimeric derivative of gallic acid occurring mostly in fruits and berries such as raspberries, strawberries, blackberries and pomegranates. 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. https://doi.org/10.1371/journal.pone.0119516.g004. Effects of gallic acid and Derivatives on Alzheimer disease . Tyman, in Encyclopedia of Separation Science, 2000. However, the proliferative marker PCNA has been suggested to be directly related with the proliferation [42], futher work will be conducted to confirm this aspect. At higher doses, GA retarded the development and growth of the embryos. The trihydric phenols, gallic acid and ethyl gallate are effective stabilizers in animal and vegetable fats and enhance the antioxygenic activity of inhibitols; they thus demonstrate the properties of both phenolic and acid inhibitors. The diverse range of applications of this simple polyphenol is due to a fine amalgam between its antioxidant and prooxidant potential. 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. Of particular interest in most studies on phenolic acids is gallic acid or 3, 4, 5- tryhydroxybenzoic acid, a naturally occurring compound found in several food sources such as gallnuts, tea, tree barks, herbs, fruits and flowers [1-5]. Herein in our experiment, the levels of ROS and MDA were seen to increase repectively from 102±13 to 305±42% and from 104±15 to 279±39% (Table 2), implicating the failure of GA to protect the malformation like the hemorrhagic liposis of cervical muscles. Conceived and designed the experiments: CLH KCC RYP. T1 - The teratogenicity and the action mechanism of gallic acid relating with brain and cervical muscles. title = "The teratogenicity and the action mechanism of gallic acid relating with brain and cervical muscles", abstract = "Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) and other flavanoids are extensively used in nutraceuticals because of their antioxidant and antiinflammatory properties. AU - Lin, Chien Hong. The incubation was continued at 37oC and RH 70%–80%. Also known as 3,4,5-trihydroxybenzoic acid, gallic acid has been reported in most plants. 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%. Yes 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. Samples (6 μL) were applied with a Linomat IV spotter and then developed to a distance of 12 cm, with M aqueous acetic acid–methanol (1:1) for 2 h. Densitometry was effected by spectrophotometry and a mercury light source (254 nm) in the absorbance mode, to determine extinction of fluorescence, as an area measurement, with a TLC scanner II (Camag) controlled by CATS software. 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]. Similar trend was found for TNF-α, ROS and MDA (Table 2). AU - Peng, Chiung Chi. Adefegha and Oboh [36] and Oboh et al. 3-DHS is available in large quantity through engineering of the shikimic acid pathway.. Metabolism. Biomedicine and pharmacotherapy - Vol. No, Is the Subject Area "Apoptosis" applicable to this article? The doses of GA used were 2, 6, 10, and 14 μM. 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). Moreover, the inhibition of carbonic anhydrase might cause the dissociation of the transferrin-carbonate-ferric ion complex, causing a severe hemolytic response [26, 27]. Macrophages are phagocytic in function and play a fundamental role in the cellular nonspecific defence mechanism. Intriguingly, treatment with gallic acid remarkably ameliorated the destabilization of liver tissue architecture caused by N-nitrosodiethylamine intoxication as evidenced by histopathological investigation. 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. View larger version. One hundred and eighty day-1 fertilized Leghorn eggs, each weighing 50 ± 2.5 g, were provided by Qing-Dang Chicken Farm (Taichung, Taiwan). Organs were fixed in 10% formalin in PBS (pH 7.4) at 4°C for 24 h and processed for paraffin embedding. Gallic acid reduced the activity of sterol 14α‐demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. Salts and esters of gallic acid are termed "gallates". It consists of three hydroxyl groups and a carboxylic acid group attached to a benzene ring. In a number of studies, the effects of proanthocyanidins on regulation of miR-33 and miR-122, known factors of lipid metabolism, has been studied by Baselga-escudero et al. The day-1 (HH Stage 46) chicks were collected. Upper row: side view. 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. Gallic acid is a very important common antioxidant tea formulation, known as an Ayurvedic herb. Normal saline was purchased fro China Pharmaceutical and Chemical Co. (Taipei, Taiwan). GA suppressed the levels of NO, PGE2, and IL-6 in LPS-induced activation of RAW264.7 cells.56 Another study showed that GA could inhibit the production of IL-6 and IL-8 induced by Fusobacterium nucleatum in human mouth epithelial cells as well as the growth of F. nucleatum, indicating that GA is a good candidate for controlling periodontal disease.57 In addition, it was reported that GA significantly decreased the cell viability of fibroblast-like synovial cells (FLS) from patients with rheumatoid arthritis. It has a role as an astringent, a cyclooxygenase 2 inhibitor, a plant metabolite, an antioxidant, an antineoplastic agent, a human xenobiotic metabolite, an EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor and an apoptosis inducer.It is a conjugate acid of a gallate. The antibacterial action mechanisms of polyphenols are summarized in Table 4. 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). The embryos were successively rinsed several times with PBS and deionized water (DW). GA and its derivatives have multiple industrial uses, such as food supplements or additives. Gallic acid is a trihydroxybenzoic acid in which the hydroxy groups are at positions 3, 4, and 5. 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 and Jureerut Daduang 2 We suggest that the activation of Ras/Raf could be the alternative GA toxicity, and our data (Fig 5) were consistent with those of Lo et al. Conversely, quercetin retains full strength PPARα and is effective in acting as an antihypercholesterolemic, indicating that the complex hypercholesterolemia of CKD is controlled not only by mitochondrial fat oxidation [39]. It also reduces ACF proliferation and/or progression exerting chemopreventive activity against colon cancer.158 Ellagic acid may be considered in a promising new class of cancer chemopreventive and therapeutic agents. Methyl gallate exhibited higher antiperoxide activity in the bulk Kilka fish oil system than gallic acid and α-tocopherol, and higher activity than gallic acid although lower activity than α-tocopherol in the oil-in-water emulsion system stabilized by soy protein isolate at 55°C. The optimal alive birth rate (or damaging rate) reached 33.3%, 39.4%, and 29.2% at 6, 10, and 14 μM GA, respectively. (A) Western blotting of the PPAR-α expression. The inhibitory effect of gallic acid on the histamine release was mediated by the modulation of cAMP and … Gallic acid is biosynthesized from 3-dehydroshikimate in a reaction catalyzed by shikimate dehydrogenase to give 3,5-didehydroshikimate, which then undergoes tautomerization to form gallate [50,51]. Data Availability: All relevant data are within the paper and its Supporting Information files. The potential growth-inhibitory signaling by Ras/Raf was activated. This included official approval from the Animal Ethics Committee of Changhua University of Education, the level of expected mortality was considered. The objective of this article is to provide an overview of natural antioxidants, their mechanisms of action, and potential applications. To determine whether GA is potentially teratogenic and can induce hemorrhages, the CEM was adopted to conduct an in vivo study. View larger version: In this window; In a new window; Download as PowerPoint Slide; FIGURE 1. [40]. Yes In developing embryos, the smooth muscle membrane, the angiogenic system, and the blood cells actively develop and differentiate in numerous developing tissues, such as nerve tissue and internal organs and blood vessels, thereby indicating the target organs of GA cytotoxicity during embryonic development. The Teratogenicity and the Action Mechanism of Gallic Acid Relating with Brain and Cervical Muscles 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 cause of mortality might be strong prooxidant bioactivity. GA at doses ≥ 1.02 mg/kg of body weight potentially causes characteristic cerebral hemolysis and liposis in the musculi longissimus cervicis. This amount of GA can be easily consumed by a pregnant woman in teas, causing a risk to the fetus. was found to be non-toxic, indicating the safety of gallic acid. 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