Pharmacological effects of gallic acid in health and disease: A mechanistic review

Document Type : Review Article

Authors

1 Department of Pharmacognosy, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

2 PhytoPharmacology Interest Group, Universal Scientific Education and Research Network, Tehran, Iran

3 Pharmaceutical Sciences Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

4 Student Research Committee, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran

5 Department of Food Science, Engineering and Technology, Faculty of Agricultural Engineering and Technology, University of Tehran, Karaj, Iran

6 Department of Pharmacy in Persian Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran

7 Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran

8 Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran

9 Toxicology and Diseases Group, The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran

10 Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

11 Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA

Abstract

Objective(s): Gallic acid is a natural phenolic compound found in several fruits and medicinal plants. It is reported to have several health-promoting effects. This review aims to summarize the pharmacological and biological activities of gallic acid in vitro and animal models to depict the pharmacological status of this compound for future studies.
Materials and Methods: All relevant papers in the English language were collected up to June 2018. The keywords of gallic acid, antioxidant, anticancer, antimicrobial, gastrointestinal-, cardiovascular-, metabolic-, neuropsychological-, and miscellaneous- diseases were searched in Google Scholar, PubMed, and Scopus.
Results: Several beneficial effects are reported for gallic acid, including antioxidant, anti-inflammatory, and antineoplastic properties. This compound has been reported to have therapeutic activities in gastrointestinal, neuropsychological, metabolic, and cardiovascular disorders.
Conclusion: Current evidence confirms the pharmacological and therapeutic interventions of gallic acid in multiple health complications; however, available data are limited to just cellular and animal studies. Future investigations are essential to further define the safety and therapeutic efficacy of gallic acid in humans.

Keywords

Main Subjects


1. Pengelly A. The Constituents of Medicinal Plants: An Introduction to the Chemistry and Therapeutics of Herbal Medicine. 2nd ed, CABI, 2004.
2. Siah M, Farzaei M, Ashrafi-Kooshk M, Adibi H, Arab S, Rashidi M, Khodarahmi R. Inhibition of guinea pig aldehyde oxidase activity by different flavonoid compounds: an in vitro study. Bioorg Chem 2016; 64:74-84.
3. Fernandes F, Salgado H. Gallic acid: review of the methods of determination and quantification. Crit Rev Anal Chem 2016; 46:257-265.
4.Choubey S, Varughese L, Kumar V, Beniwal V. Medicinal importance of gallic acid and its ester derivatives: a patent review. Pharm Pat Anal 2015; 4:305-315.
5. Borges A, Ferreira C, Saavedra M, Simoes M. Antibacterial activity and mode of action of ferulic and gallic acids against pathogenic bacteria. Microb Drug Resist 2013; 19:256-265.
6. Cueva C, Moreno-Arribas M, Martin-Alvarez P, Bills G, Francisca Vicente M, Basilio A, et al. Antimicrobial activity of phenolic acids against commensal, probiotic and pathogenic bacteria. Res Microbiol 2010; 161:372-382.
7. Farag M, Al‐Mahdy D, Salah El Dine R, Fahmy S, Yassin A, Porzel A, et al. Structure activity relationships of antimicrobial gallic acid derivatives from pomegranate and acacia fruit extracts against potato bacterial wilt pathogen. Chem Biodivers 2015; 12:955-962.
8. Rivero-Buceta E, Carrero P, Doyagüez E, Madrona A, Quesada E, Camarasa M, et al. Linear and branched alkyl-esters and amides of gallic acid and other (mono-, di- and tri-) hydroxy benzoyl derivatives as promising anti-HCV inhibitors. Eur J Med Chem 2015; 92:656-671.
9. Sanchez-Maldonado A, Schieber A, Ganzle M. Structure–function relationships of the antibacterial activity of phenolic acids and their metabolism by lactic acid bacteria. J Appl Microbiol 2011; 111:1176-1184.
10. Shao D, Li J, Li J, Tang R, Liu L, Shi J, et al. Inhibition of gallic acid on the growth and biofilm formation of Escherichia coli and Streptococcus mutans. J Food Sci 2015; 80: 1299-1305.
11. Borges A, Saavedra MJ, Simoes M. The activity of ferulic and gallic acids in biofilm prevention and control of pathogenic bacteria. Biofouling 2012; 28:755-767.
12. Kang M, Oh J, Kang I, Hong S, Choi C. Inhibitory effect of methyl gallate and gallic acid on oral bacteria. J Microbiol 2008; 46:744-750.
13. Teodoro G, Ellepola K, Seneviratne C. potential use of phenolic acids as anti-candida agents-a review. Front Microbiol 2015; 6:1420. doi: 10.3389/fmicb.2015.01420. eCollection 2015.
14. Oh B, Jeon E. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds. Front Microbiol 2015; 13:1129. doi: 10.3389/fmicb.2015.01129. eCollection 2015.
15. Nohynek L, Alakomi H, Kahkonen M, Heinonen M, Helander I, Oksman-Caldentey K, et al. Berry phenolics: antimicrobial properties and mechanisms of action against severe human pathogens. Nutr Cancer 2006; 54:18-32.
16. Godstime C, Felix O, Augustina O, Christopher O. Mechanisms of antimicrobial actions of phytochemicals against enteric pathogens, J Pharm Chem Biol Sci 2014; 2:77-85.
17. Kubo I, Fujita K, Nihei K, Masuoka N. Non-antibiotic antibacterial activity of dodecyl gallate. Bioorg Med Chem 2003; 11:573-580.
18. Modi M, Goel T, Das T, Malik S, Suri S, Rawat AK, et al. Ellagic acid & gallic acid from Lagerstroemia speciosa L. inhibit HIV-1 infection through inhibition of HIV-1 protease & reverse transcriptase activity. Indian J Med Res 2013; 137:540-548.
19. Singh A, Pal T. Docking analysis of gallic acid derivatives as HIV-1 protease inhibitors. Int J Bioinform Res Appl 2015; 11:540-546.
20. Ahn C, Jung W, Park S, Kim Y, Kim W, Je J. Gallic acid-g-chitosan modulates inflammatory responses in LPS-stimulated RAW264.7 cells via NF-kappaB, AP-1, and MAPK pathways. Inflammation 2016; 39:366-374.
21. Flausino O, Dufau L, Regasini L, Petronio M, Silva D, Rose T, et al. Alkyl hydroxybenzoic acid derivatives that inhibit HIV-1 protease dimerization. Curr Med Chem 2012; 19:4534-4540.
22. Kratz J, Andrighetti-Frohner C, Kolling D, Leal P, Cirne-Santos C, Yunes R, et al. Anti-HSV-1 and anti-HIV-1 activity of gallic acid and pentyl gallate. Mem Inst Oswaldo Cruz 2008; 103:437-442.
23. Zuo G, Li Z, Chen L, Xu X. In vitro anti-HCV activities of Saxifraga melanocentra and its related polyphenolic compounds. Antivir Chem Chemother 2005; 16:393-398.
24. Govea Salas M, Rivas Estilla A, Morlett Chávez J, Lozano Sepúlveda S, Rodríguez Herrera R, Aguilar González C. P420 gallic acid has antiviral effect against hepatitis C virus (HCV), which is mediated by its antioxidant activity. J Hepatol 2014; 60:S208.
25. Govea-Salas M, Rivas-Estilla A, Rodriguez-Herrera R, Lozano-Sepulveda S, Aguilar-Gonzalez C, Zugasti-Cruz A, et al. Gallic acid decreases hepatitis C virus expression through its antioxidant capacity. Exp Ther Med 2016; 11:619-624.
26. Hsu W, Chang S, Lin L, Li C, Richardson C, Lin C, et al. Limonium sinense and gallic acid suppress hepatitis C virus infection by blocking early viral entry. Antiviral Res 2015; 118:139-147.
27. Lee J, Oh M, Seok J, Kim S, Lee D, Bae G, et al. Antiviral effects of black raspberry (Rubus coreanus) seed and its gallic acid against influenza virus infection. Viruses 2016; 6. pii: E157. doi: 10.3390/v8060157.
28. Ndjonka D, Abladam E, Djafsia B, Ajonina-Ekoti I, Achukwi M, Liebau E. Anthelmintic activity of phenolic acids from the axlewood tree Anogeissus leiocarpus on the filarial nematode Onchocerca ochengi and drug-resistant strains of the free-living nematode Caenorhabditis elegans. J Helminthol 2014; 88:481-488.
29. Abouelhassan Y, Garrison A, Bai F, Norwood V, Nguyen M, Jin S, et al. A Phytochemical-halogenated quinoline combination therapy strategy for the treatment of pathogenic bacteria. Chem Med Chem 2015; 10:1157-1162.
30. Li D, Liu Z, Yuan Y, Liu Y, Niu F. Green synthesis of gallic acid-coated silver nanoparticles with high antimicrobial activity and low cytotoxicity to normal cells. Process Biochem 2015; 50:357-366.
31. Lima V, Oliveira-Tintino C, Santos E, Morais L, Tintino S, Freitas T, et al. Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: gallic acid, caffeic acid and pyrogallol. Microb Pathog 2016; 99:56-61.
32. Lee D, Eom S, Kim Y, Kim H, Yim M, Lee S, et al. Antibacterial and synergic effects of gallic acid-grafted-chitosan with beta-lactams against methicillin-resistant Staphylococcus aureus (MRSA). Can J Microbiol 2014; 60:629-638.
33. Choi J, Kang O, Lee Y, Oh Y, Chae H, Jang H, et al. In vitro activity of methyl gallate isolated from galla rhois alone and in combination with ciprofloxacin against clinical isolates of salmonella. J microbiol biotechnol 2008; 18:1848-1852.
34. Shibata H, Kondo K, Katsuyama R, Kawazoe K, Sato Y, Murakami K, et al. Alkyl gallates, intensifiers of β-lactam susceptibility in methicillin-resistant Staphylococcus aureus. Antimicrob agents chemother 2005; 49:549-555.
35. Kasper D, Hauser S, Jameson J, Fauci A, Longo D, Loscalzo J. Harrison’s Principles of Internal Medicine, 19th ed. Mc Graw Hill, 2015.
36. Farzaei M, Bahramsoltani R, Rahimi R. Phytochemicals as adjunctive with conventional anticancer therapies. Curr Pharm Des 2016; 22:4201-4218.
37. Shokoohinia Y, Jafari F, Mohammadi Z, Bazvandi L, Hosseinzadeh L, Chow N, et al. Potential anticancer properties of osthol: a comprehensive mechanistic review. Nutrients 2018; 10:36.
38. Ahmedin J, Freddie B, Melissa M, Jacques F, Elizabeth W, David F. Global cancer statistics. Cancer J Clin 2011; 61:69-90.
39. Giftson J, Jayanthi S, Nalini N. Chemopreventive efficacy of gallic acid, an antioxidant and anticarcinogenic polyphenol, against 1, 2-dimethyl hydrazine induced rat colon carcinogenesis. Invest New Drugs 2010; 28:251-259.
40. Subramanian V, Venkatesan B, Tumala A, Vellaichamy E. Topical application of gallic acid suppresses the 7, 12-DMBA/croton oil induced two-step skin carcinogenesis by modulating anti-oxidants and MMP-2/MMP-9 in Swiss albino mice. Food Chem Toxicol 2014; 66:44-55.
41. Balch C, Gershenwald J, Soong S, Thompson J, Atkins M, Byrd D, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27:6199-6206.
42. Liao C, Lai K, Huang A, Yang J, Lin J, Wu S, et al. Gallic acid inhibits migration and invasion in human osteosarcoma U-2 OS cells through suppressing the matrix metalloproteinase-2/-9, protein kinase B (PKB) and PKC signaling pathways. Food Chem Toxicol 2012; 50:1734-1740.
43. Nemec M, Kim H, Marciante A, Barnes R, Talcott S, Mertens-Talcott S. Pyrogallol, an absorbable microbial gallotannins-metabolite and mango polyphenols (Mangifera Indica L.) suppress breast cancer ductal carcinoma in situ proliferation in vitro. Food Funct 2016; 7:3825-3833.
44. Da Silva S, Chaar J, Yano T. Chemotherapeutic potential of two gallic acid derivative compounds from leaves of Casearia sylvestris Sw (Flacourtiaceae). Eur J Pharmacol 2009; 608:76-83.
45. Huang P, Hseu Y, Lee M, Kumar K, Wu C, Hsu L, et al. In vitro and in vivo activity of gallic acid and Toona sinensis leaf extracts against HL-60 human premyelocytic leukemia. Food Chem Toxicol 2012; 50:3489-3497.
46. Jagan S, Ramakrishnan G, Anandakumar P, Kamaraj S, Devaki T. Antiproliferative potential of gallic acid against diethylnitrosamine-induced rat hepatocellular carcinoma. Mol Cell Biochem 2008; 319:51-59.
47. Mard S, Mojadami S, Farbood Y, Gharib Naseri M. The anti-inflammatory and anti-apoptotic effects of gallic acid against mucosal inflammation- and erosions-induced by gastric ischemia-reperfusion in rats. Vet Res Forum 2015; 6:305-311.
48. Pal C, Bindu S, Dey S, Alam A, Goyal M, Iqbal MS, et al. Gallic acid prevents nonsteroidal anti-inflammatory drug-induced gastropathy in rat by blocking oxidative stress and apoptosis. Free Radicals Biol Med 2010; 49:258-267.
49. Chatterjee A, Chatterjee S, Biswas A, Bhattacharya S, Chattopadhyay S, Bandyopadhyay SK. Gallic acid enriched fraction of Phyllanthus emblica potentiates indomethacin-induced gastric ulcer healing via e-NOS-dependent pathway. Evid Based Complement Alternat Med 2012; 2012:487380.
50. Pandurangan A, Mohebali N, Norhaizan M, Looi C. Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice. Drug Des Devel Ther 2015b; 9:3923-3934.
51. Pandurangan A, Mohebali N, Mohd. Esa N, Looi C, Ismail S, Saadatdoust Z. Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: possible mechanisms. Int Immunopharmacol 2015a; 28:1034-1043.
52. Park J, Han W, Park J, Choi S, Choi J. Changes in hepatic drug metabolizing enzymes and lipid peroxidation by methanol extract and major compound of Orostachys japonicus. J Ethnopharmacol 2005; 102:313-318.
53. Anand K, Singh B, Saxena A, Chandan B, Gupta V, Bhardwaj V. 3,4,5-trihydroxy benzoic acid (gallic acid), the hepatoprotective principle in the fruits ofterminalia belerica-bioassay guided activity. Pharmacol Res 1997; 36:315-321.
54. Kartkaya K, Oglakci A, Senturk H, Bayramoglu G, Canbek M, Kanbak G. Investigation of the possible protective role of gallic acid on paraoxanase and arylesterase activities in livers of rats with acute alcohol intoxication. Cell Biochem Funct 2013; 31:208-213.
55. Oyagbemi A, Omobowale O, Asenuga E, Akinleye A, Ogunsanwo R, Saba A. Cyclophosphamide-induced hepatotoxicity in wistar rats: the modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical. Int J Prev Med 2016; 7:51. doi:[10.4103/2008-7802.177898].
56. Reckziegel P, Dias V, Benvegnú D, Boufleur N, Barcelos R, Segat H, et al. Antioxidant protection of gallic acid against toxicity induced by Pb in blood, liver and kidney of rats. Toxicol Rep 2016; 3:351-356.
57. Bayramoglu G, Kurt H, Bayramoglu A, Gunes H, Degirmenci I, Colak S. Preventive role of gallic acid on hepatic ischemia and reperfusion injury in rats. Cytotechnology 2015; 67:845-849.
58. Priscilla D, Prince P. Cardioprotective effect of gallic acid on cardiac troponin-T, cardiac marker enzymes, lipid peroxidation products and antioxidants in experimentally induced myocardial infarction in wistar rats. Chem Biol Interact 2009; 179:118-124.
59. Gandhi G, Jothi G, Antony PJ, Balakrishna K, Paulraj M, Ignacimuthu S, et al. Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARgamma in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway. Eur J Pharmacol 2014; 745:201-216.
60. Kade I, Ogunbolude Y, Kamdem J, Rocha J. Influence of gallic acid on oxidative stress-linked streptozotocin-induced pancreatic dysfunction in diabetic rats. J Basic Clin Physiol Pharmacol 2014; 25:35-45.
61. Bak E, Kim J, Jang S, Woo G, Yoon H, Yoo Y, et al. Gallic acid improves glucose tolerance and triglyceride concentration in diet-induced obesity mice. Scand J Clin Lab Invest 2013; 73:607-614.
62. Hsu C, Yen G. Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats. Br J Nutr 2007; 98:727-735.
63. Huang D, Chang W, Wu J, Shih R, Shen S. Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet. Nutr Res 2016; 36:150-160.
64. Ban J, Nguyen H, Lee H, Cho S, Ju H, Kim J. Neuroprotective properties of gallic acid from Sanguisorbae radix on amyloid beta protein (25-35)-induced toxicity in cultured rat cortical neurons. Biol Pharm Bull 2008; 31:149-153.
65. Mansouri M, Farbood Y, Sameri M, Sarkaki A, Naghizadeh B, Rafeirad M. Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. Food chem 2013; 138:1028-1033.
66. Nagpal K, Singh S, Mishra D. Nanoparticle mediated brain targeted delivery of gallic acid: in vivo behavioral and biochemical studies for protection against scopolamine-induced amnesia. Drug Deliv 2013; 20:112-119.
67. Kang M, Kang N, Jang Y, Lee K, Lee H. Gallic acid induces neuronal cell death through activation of c-Jun N-terminal kinase and downregulation of Bcl-2. Ann N Y Acad Sci 2009; 1171:514-520.
68. Crispo J, Piché M, Ansell D, Eibl J, Tai I, Kumar A. Protective effects of methyl gallate on H2O2-induced apoptosis in PC12 cells. Biochem Biophys Res Commun 2010; 393:773-778.
69. Nazir N, Koul S, Qurishi M, Taneja S, Ahmad S, Bani S, et al. Immunomodulatory effect of bergenin and norbergenin against adjuvant-induced arthritis—a flowcytometric study. J Ethnopharmacol 2007; 112:401-405.
70. Santos A, De Campos R, Miguel O, Cechinel-Filho V, Yunes R, Calixto J. The involvement of K+ channels and Gi/o protein in the antinociceptive action of the gallic acid ethyl ester. Eur J Pharmacol 1999; 379:7-17.
71. Kroes B, van den Berg A, Quarles van Ufford H, van Dijk H, Labadie R. Anti-inflammatory activity of gallic acid. Planta Med 1992; 58:499-504.
72. Choi K, Lee Y, Jung M, Kwon S, Kim M, Jun W, et al. Gallic acid suppresses lipopolysaccharide-induced nuclear factor-κB signaling by preventing RelA acetylation in A549 lung cancer cells. Mol Cancer Res 2009; 7:2011-2021.
73. Wen L, Qu T, Zhai K, Ding J, Hai Y, Zhou J. Gallic acid can play a chondroprotective role against AGE-induced osteoarthritis progression. J Orthop Sci 2015; 20:734-741.
74. Canbek M, Bayramoglu G, Senturk H, Oztopcu Vatan A, Uyanoglu M, Ceyhan E, et al. The examination of protective effects of gallic acid against damage of oxidative stress during induced-experimental renal ischemia-reperfusion in experiment. Bratisl Lek Listy 2014; 115:557-562.
75. Akomolafe S, Akinyemi A, Anadozie S. Phenolic acids (gallic and tannic acids) modulate antioxidant status and cisplatin induced nephrotoxicity in rats. Int Sch Res Notices 2014; 2014:984709.
76. Olusoji M, Oyeyemi O, Asenuga E, Omobowale T, Ajayi O, Oyagbemi A. Protective effect of Gallic acid on doxorubicin-induced testicular and epididymal toxicity. Andrologia 2016;49. doi: 10.1111/and.12635.
77. Prasad L, Khan T, Jahangir T, Sultana S. Effect of gallic acid on renal biochemical alterations in male Wistar rats induced by ferric nitriloacetic acid. Hum Exp Toxicol 2006; 25:523-529.
78. Yousuf M, Vellaichamy E. Protective activity of gallic acid against glyoxal -induced renal fibrosis in experimental rats. Toxicol Rep 2015; 2:1246-1254.
79. Peng C, Hsieh C, Wang H, Chung J, Chen K, Peng R. Ferulic acid is nephrodamaging while gallic acid is renal protective in long term treatment of chronic kidney disease. Clin Nutr 2012; 31:405-414.
80. Nikbakht J, Hemmati A, Arzi A, Mansouri M, Rezaie A, Ghafourian M. Protective effect of gallic acid against bleomycin-induced pulmonary fibrosis in rats. Pharmacol Rep 2015; 67:1061-1067.
81. Gandhi N, Nair C. Protection of DNA and membrane from gamma radiation induced damage by gallic acid. Mol Cell Biochem 2005; 278:111-117.
82. Nair G, Nair C. Radioprotective effects of gallic acid in mice. Biomed Res Int 2013; 2013:953079. doi: 10.1155/2013/953079.
83. Kumar K, Vani M, Wang S, Liao J, Hsu L, Yang H, et al. In vitro and in vivo studies disclosed the depigmenting effects of gallic acid: a novel skin lightening agent for hyperpigmentary skin diseases. Biofactors 2013; 39:259-270.
84. Hwang E, Park S, Lee H, Lee T, Sun Z, Yi T. Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless mice. Phytother Res 2014; 28:1778-1788.
85. Shaik A, Rasool S, Reddy A, Kareem M, Saayi Krushna G, Lakshmi Devi K. Cardioprotective effect of HPLC standardized ethanolic extract of Terminalia pallida fruits against isoproterenol-induced myocardial infarction in albino rats. J Ethnopharmacol 2012; 141:33-40.
86. Prince P, Priscilla H, Devika P. Gallic acid prevents lysosomal damage in isoproterenol induced cardiotoxicity in wistar rats. Eur J Pharmacol 2009; 615:139-143.
87. Padma V, Poornima P, Prakash C, Bhavani R. Oral treatment with gallic acid and quercetin alleviates lindane-induced cardiotoxicity in rats. Can J Physiol Pharmacol 2013; 91:134-140.
88. Yeh C, Ching L, Yen G. Inducing gene expression of cardiac antioxidant enzymes by dietary phenolic acids in rats. J Nutr Biochem 2009; 20:163-171.
89. Umadevi S, Gopi V, Elangovan V. Regulatory mechanism of gallic acid against advanced glycation end products induced cardiac remodeling in experimental rats. Chem Biol Interact 2014; 208:28-36.
90. Patel S, Goyal R. Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats. Pharmacognosy Res 2011; 3:239-245.
91. Sutra T, Oiry C, Azay-Milhau J, Youl E, Magous R, Teissedre PL, et al. Preventive effects of nutritional doses of polyphenolic molecules on cardiac fibrosis associated with metabolic syndrome: involvement of osteopontin and oxidative stress. J Agric Food Chem 2008; 56:11683-11687.
92. El-Hussainy E, Hussein A, Abdel-Aziz A, El-Mehasseb I. Effects of aluminum oxide (Al2O3) nanoparticles on ECG, myocardial inflammatory cytokines, redox state, and connexin 43 and lipid profile in rats: possible cardioprotective effect of gallic acid. Can J Physiol Pharmacol 2016; 94:868-878.
93. Badavi M, Sadeghi N, Dianat M, Samarbafzadeh A. Effects of gallic Acid and cyclosporine a on antioxidant capacity and cardiac markers of rat isolated heart after ischemia/reperfusion. Iran Red Crescent Med J 2014; 16:e16424. doi:[10.5812/ircmj.16424].
94. Jin L, Lin M, Piao Z, Cho J, Kim G, Choi S, et al. Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2. J Hypertens 2017; 35: 1502-1512.
95. Ogunsanwo O, Oyagbemi A, Omobowale T, Asenuga E, Saba A. Biochemical and electrocardiographic studies on the beneficial effects of gallic acid in cyclophosphamide-induced cardiorenal dysfunction. J Complement Integr Med 2017; 144. doi: 10.1515/jcim-2016-0161.
96. Eler G, Peralta R, Bracht A. The action of n-propyl gallate on gluconeogenesis and oxygen uptake in the rat liver. Chem Bio Interact 2009; 181:390-399.
97. Gupta N, Gupta S, Mahmood A. Gallic acid inhibits brush border disaccharidases in mammalian intestine. Nutr Res 2007; 27:230-235.
98. Hsieh S, Wu C, Wu C, Yen J, Liu M, Hsueh C. Gallic acid selectively induces the necrosis of activated hepatic stellate cells via a calcium-dependent calpain I activation pathway. Life Sci 2014; 102: 55-64.
99. Kanbak G, Canbek M, Oglakci A, Kartkaya K, Senturk H, Bayramoglu G, et al. Preventive role of gallic acid on alcohol dependent and cysteine protease-mediated pancreas injury. Mol Biol Rep 2012; 39:10249-10255.
100. Pal C, Bindu S, Dey S, Alam A, Goyal M, Iqbal M, et al. Tryptamine-gallic acid hybrid prevents non-steroidal anti-inflammatory drug-induced gastropathy: correction of mitochondrial dysfunction and inhibition of apoptosis in gastric mucosal cells. J Biol Chem 2012; 287:3495-3509.
101. Rasool M, Sabina E, Ramya S, Preety P, Patel S, Mandal N, et al. Hepatoprotective and antioxidant effects of gallic acid in paracetamol-induced liver damage in mice. J Pharm Pharmacol 2010; 62:638-643.
102. Sachdeva M, Chadha R, Kumar A, Karan M, Singh T, Dhingra S. Hepatoprotective effect of trimethylgallic acid esters against carbon tetrachloride-induced liver injury in rats. Indian J Exp Biol 2015; 53:803-809.
103. Sen S, De B, Devanna N, Chakraborty R. Total phenolic, total flavonoid content, and antioxidant capacity of the leaves of Meyna spinosa Roxb., an Indian medicinal plant. Chin J Nat Med 2013; 11:149-157.
104. Wang Y, Chung F, Lee S, Dykes G. Inhibition of attachment of oral bacteria to immortalized human gingival fibroblasts (HGF-1) by tea extracts and tea components. BMC Res Notes 2013; 6:143. https://doi.org/10.1186/1756-0500-6-143.
105. Zhao X, Wang Y, Sun Y. Quantitative and qualitative determination of Liuwei Dihuang tablets by HPLC-UV-MS-MS. J Chromatogr Sci 2007; 45:549-552.
106. Sugimoto K, Sakamoto S, Nakagawa K, Hayashi S, Harada N, Yamaji R, et al. Suppression of inducible nitric oxide synthase expression and amelioration of lipopolysaccharide-induced liver injury by polyphenolic compounds in Eucalyptus globulus leaf extract. Food Chem 2011; 125:442-446.
107. Tung Y, Wu J, Hsieh C, Chen P, Chang S. Free radical-scavenging phytochemicals of hot water extracts of Acacia confusa leaves detected by an on-line screening method. Food Chem 2009; 115:1019-1024.
108. Padma V, Sowmya P, Felix T, Baskaran R, Poornima P. Protective effect of gallic acid against lindane induced toxicity in experimental rats. Food Chem Toxicol 2011; 49:991-998.
109. Nirala S, Li P, Bhadauria M, Guo G. Combined effects of gallic acid and propolis on beryllium-induced hepatorenal toxicity. Integr Zool 2008; 3:194-207.
110. Latha R, Daisy P. Insulin-secretagogue, antihyperlipidemic and other protective effects of gallic acid isolated from Terminalia bellerica Roxb. in streptozotocin-induced diabetic rats. Chem Biol Interac 2011; 189: 112-118.
111. Oi Y, Hou I, Fujita H, Yazawa K. Antiobesity effects of Chinese black tea (Pu-erh tea) extract and gallic acid. Phytother Res 2012; 26:475-481.
112. Punithavathi V, Prince P, Kumar R, Selvakumari J. Antihyperglycaemic, antilipid peroxidative and antioxidant effects of gallic acid on streptozotocin induced diabetic wistar rats. Eur J Pharmacol 2011; 650:465-471.
113. Punithavathi V, Prince P, Kumar M, Selvakumari C. Protective effects of gallic acid on hepatic lipid peroxide metabolism, glycoprotein components and lipids in streptozotocin-induced type II diabetic wistar rats. J Biochem Mol Toxicol 2011; 25:68-76.
114. Ramkumar K, Vijayakumar R, Vanitha P, Suganya N, Manjula C, Rajaguru P, et al. Protective effect of gallic acid on alloxan-induced oxidative stress and osmotic fragility in rats. Hum Exp Toxicol 2014; 33:638-649.
115. Mohammed A, Koorbanally N, Islam M. Phytochemistry, antioxidative activity and inhibition of key enzymes linked to type 2 diabetes by various parts of Aframomum melegueta in vitro. Acta Pol Pharm 2016; 73:403-417.
116. Ahad A, Ahsan H, Mujeeb M, Siddiqui W. Gallic acid ameliorates renal functions by inhibiting the activation of p38 MAPK in experimentally induced type 2 diabetic rats and cultured rat proximal tubular epithelial cells. Chem Bio Interact 2015; 240:292-303.
117. de Oliveira L, de Oliveira T, da Costa R, de Souza Gil E, Costa E, Passaglia C, et al. The vasorelaxant effect of gallic acid involves endothelium-dependent and -independent mechanisms. Vascul Pharmacol 2016; 81:69-74.
118. Mansouri M, Naghizadeh B, Ghorbanzadeh B, Farbood Y, Sarkaki A, Bavarsad K. Gallic acid prevents memory deficits and oxidative stress induced by intracerebroventricular injection of streptozotocin in rats. Pharmacol Biochem Behav 2013; 111:90-96.
119. Mansouri M, Soltani M, Naghizadeh B, Farbood Y, Mashak A, Sarkaki A. A possible mechanism for the anxiolytic-like effect of gallic acid in the rat elevated plus maze. Pharmacol Biochem Behav 2014; 117:40-46.
120. Nabavi S, Habtemariam S, Jafari M, Sureda A, Nabavi S. Protective role of gallic acid on sodium fluoride induced oxidative stress in rat brain. Bull Environ Contam Toxicol 2012; 89:73-77.
121. Naghizadeh B, Mansouri M. Protective effects of gallic acid against streptozotocin-induced oxidative damage in rat striatum. Drug Res (Stuttg) 2015; 65:515-520.
122. Yang Y, Wang Z, Zheng J, Wang R. Protective effects of gallic acid against spinal cord injury-induced oxidative stress. Mol Med Rep 2015; 12:3017-3024.
123. Ortega-Arellano H, Jimenez-Del-Rio M, Velez-Pardo C. Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson’s disease model. Genet Mol Biol 2013; 36:608-615.
124. Reckziegel P, Peroza L, Schaffer LF, Ferrari M, de Freitas C, Burger M, et al. Gallic acid decreases vacuous chewing movements induced by reserpine in rats. Pharmacol Biochem Behav 2013; 104:132-137.
125. Reckziegel P, Dias VT, Benvegnu D, Boufleur N, Barcelos R, Segat H, et al. Locomotor damage and brain oxidative stress induced by lead exposure are attenuated by gallic acid treatment. Toxicol Lett 2011; 203:74-81.
126. Parihar P, Jat D, Ghafourifar P, Parihar M. Efficiency of mitochondrially targeted gallic acid in reducing brain mitochondrial oxidative damage. Cell Mol Biol 2014; 60:35-41.
127. Sun H, Zhang Y, Xie X, Che Y. Biochemical studies for improved antioxidant and antidepressant-like activity. Drug Deliv 2012; 19:378-391.
129. Dhingra D, Chhillar R, Gupta A. Antianxiety-like activity of gallic acid in unstressed and stressed mice: possible involvement of nitriergic system. Neurochem Res 2012; 37:487-494.
130. Farbood Y, Sarkaki A, Hashemi S, Mansouri M, Dianat M. The effects of gallic acid on pain and memory following transient global ischemia/reperfusion in wistar rats. Avicenna J Phytomed 2013; 3:329-340.
131. Hajimoradi M, Fazilati M, Gharib-Naseri M, Sarkaki A. Gallic acid and exercise training improve motor function, nerve conduction velocity but not pain sense reflex after experimental sciatic nerve crush in male rats. Avicenna J Phytomed 2015; 5:288-297.
132. Hajipour S, Sarkaki A, Farbood Y, Eidi A, Mortazavi P, Valizadeh Z. Effect of gallic acid on dementia type of Alzheimer disease in rats: electrophysiological and histological studies. Basic Clin Neurosci 2016; 7:97-106.
133. Kade I, Rocha J. Gallic acid modulates cerebral oxidative stress conditions and activities of enzyme-dependent signaling systems in streptozotocin-treated rats. Neurochem Res 2013; 38:761-771.
134. Kim M, Seong A, Yoo J, Jin C, Lee Y, Kim Y, et al. Gallic acid, a histone acetyltransferase inhibitor, suppresses beta-amyloid neurotoxicity by inhibiting microglial-mediated neuroinflammation. Mol Nutr Food Res 2011; 55:1798-1808.
135. Korani M, Farbood Y, Sarkaki A, Fathi Moghaddam H, Mansouri M. Protective effects of gallic acid against chronic cerebral hypoperfusion-induced cognitive deficit and brain oxidative damage in rats. Eur J Pharmacol 2014; 733:62-67.
136. Lu Z, Nie G, Belton P, Tang H, Zhao B. Structure–activity relationship analysis of antioxidant ability and neuroprotective effect of gallic acid derivatives. Neurochem Int 2006; 48:263-274.
137. Zhang Q, Chen W, Zhao J, Xi W. Functional constituents and antioxidant activities of eight Chinese native goji genotypes. Food Chem 2016; 200:230-236.
138. Yigitturk G, Acara A, Erbas O, Oltulu F, Yavasoglu N, Uysal A, et al. The antioxidant role of agomelatine and gallic acid on oxidative stress in STZ induced type I diabetic rat testes. Biomed Pharmacother 2017; 87:240-246.
139. Giftson Senapathy J, Jayanthi S, Viswanathan P, Umadevi P, Nalini N. Effect of gallic acid on xenobiotic metabolizing enzymes in 1,2-dimethyl hydrazine induced colon carcinogenesis in Wistar rats – a chemopreventive approach. Food Chem Toxicol 2011; 49:887-892.
140. Ji B, Hsu W, Yang J, Hsia T, Lu C, Chiang J, et al. Gallic acid induces apoptosis via caspase-3 and mitochondrion-dependent pathways in vitro and suppresses lung xenograft tumor growth in vivo. J Agric Food Chem 2009; 57:7596-7604.
141. Kawada M, Ohno Y, Ri Y, Ikoma T, Yuugetu H, Asai T,                     et al. Anti-tumor effect of gallic acid on LL-2 lung cancer cells transplanted in mice. Anticancer Drugs 2001; 12:847-852.
142. Nakamura E, Kurosaki F, Arisawa M, Mukainaka T, Takayasu J, Okuda M, et al. Cancer chemopreventive effects of a Brazilian folk medicine, Juca, on in vivo two-stage skin carcinogenesis. J Ethnopharmacol 2002; 81:135-137.
143. Thiele W, Rothley M, Teller N, Jung N, Bulat B, Plaumann D, et al. Delphinidin is a novel inhibitor of lymphangiogenesis but promotes mammary tumor growth and metastasis formation in syngeneic experimental rats. Carcinogenesis 2013; 34:2804-2813.