Anti-inflammatory effect of gallic acid on HaCaT keratinocytes through the inhibition of MAPK-, NF-kB-, and Akt-dependent signaling pathways

Authors

  • Polly Ho-Ting Shiu Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China. https://orcid org/0000-0003-4164-8797
  • Chengwen Zheng Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China. https://orcid.org/0000-0002-2633-643X
  • Panthakarn Rangsinth Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China. https://orcid.org/0000-0001-7255-9012
  • Wen Wang Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China. https://orcid.org/0000-0002-7060-0779
  • Jingjing Li Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hong Kong SAR, China.
  • Renkai Li Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China. https://orcid.org/0000-0001-9770-2591
  • George Pak-Heng Leung Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China.

DOI:

https://doi.org/10.3329/bjp.v18i1.63052

Keywords:

Anti-inflammatory, Antioxidant, Chemokines, Gallic acid, Keratinocytes

Abstract

The objectives of the present study were to evaluate the antioxidant and anti-inflammatory effects of gallic acid, a naturally occurring triphenolic compound, on HaCaT keratinocytes and study its mechanisms of action. The results showed that gallic acid at concentrations lower than 30 µM was non-toxic to HaCaT cells, reduced the intracellular level of reactive oxygen species, and suppressed the release of chemokines interleukin-8 and monocyte chemoattractant protein-1 in tumor necrosis factor-α- and interferon-γ-stimulated HaCaT keratinocytes. In addition, gallic acid reduced the total protein expression of NF-κB and inhibited the phosphorylation of ERK1/2, p38 MAPK, and Akt in stimulated HaCaT keratinocytes. In conclusion, our study revealed that gallic acid exhibited antioxidant and anti-inflammatory effects on keratinocytes, probably through the inhibition of MAPK-, NF-κB-, and Akt-dependent signaling pathways.

Downloads

Download data is not yet available.
Abstract
177
Download
327

References

Al Zahrani NA, El-Shishtawy RM, Asiri AM. Recent developments of gallic acid derivatives and their hybrids in medicinal chemistry: A review. Eur J Med Chem. 2020; 204: 112609.

Allen RG, Tresini M. Oxidative stress and gene regulation. Free Radic Biol Med. 2000; 28: 463-99.

Badhani B, Sharma N, Kakkar R. Gallic acid: A versatile antioxidant with promising therapeutic and industrial applications. RSC Adv. 2015; 5: 27540-57.

Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 1994; 12: 141–79.

Bahuguna A, Khan I, Bajpai VK, Kang SC. MTT assay to evaluate the cytotoxic potential of a drug. Bangladesh J Pharmacol. 2017; 12: 115-18.

Chabot-Fletcher M, Breton J, Lee J, Young P, Griswold DE. Interleukin-8 production is regulated by protein kinase C in human keratinocytes. J Invest Dermatol. 1994; 103: 509–15.

Chan BC, Li LF, Hu SQ, Wat E, Wong EC, Zhang VX, Lau CB, Wong CK, Hon KL, Hui PC, Leung PC. Gallic acid is the major active component of cortex moutan in inhibiting immune maturation of human monocyte-derived dendritic cells. Molecules 2015; 20: 16388-403.

Chao J, Cheng HY, Chang ML, Huang SS, Liao JW, Cheng YC, Peng WH, Pao LH. Gallic acid ameliorated impaired lipid homeostasis in a mouse model of high-fat diet- and streptozotocin-induced NAFLD and diabetes through improvement of beta-oxidation and ketogenesis. Front Pharmacol. 2020; 11: 606759.

Cheng Y, Li X, Tse HF, Rong J. Gallic acid-L-leucine conjugate protects mice against LPS-Induced inflammation and sepsis via correcting proinflammatory lipid mediator profiles and oxidative stress. Oxid Med Cell Longev. 2018; 1081287.

Cho EJ, Yokozawa T, Rhyu DY, Kim SC, Shibahara N, Park JC. Study on the inhibitory effects of Korean medicinal plants and their main compounds on the 1,1-diphenyl-2-picryl-hydrazyl radical. Phytomedicine 2003; 10: 544-51.

Domíngue R, Zhang L, Rocchetti G, Lucini L, Pateiro M, Munekata PES, Lorenzo JM. Elderberry (Sambucus nigra L.) as potential source of antioxidants: Characterization, optimization of extraction parameters and bioactive properties. Food Chem. 2020; 330: 127266.

Fan Y, Piao CH, Hyeon E, Jung SY, Eom JE, Shin HS, Song CH, Chai OH. Gallic acid alleviates nasal inflammation via activation of Th1 and inhibition of Th2 and Th17 in a mouse model of allergic rhinitis. Int Immunopharmacol. 2019; 70: 512-19.

Gu R, Zhang M, Meng H, Xu D, Xie Y. Gallic acid targets acute myeloid leukemia via Akt/mTOR-dependent mitochondrial respiration inhibition. Biomed Pharmacother. 2018; 105: 491-97.

Han EJ, Fernando IPS, Kim HS, Lee DS, Kim A, Je JG, Seo MJ, Jee YH, Jeon YJ, Kim SY. (–)-Loliolide isolated from Sargassum horneri suppressed oxidative stress and inflammation by activating Nrf2/HO-1 signaling in IFN-γ/TNF-α-stimulated HaCaT keratinocytes. Antioxidants 2021; 10: 856.

Hu G, Zhou X. Gallic acid ameliorates atopic dermatitis-like skin inflammation through immune regulation in a mouse model. Clin Cosmet Investig Dermatol. 2021; 14: 1675-83.

Kahkeshani N, Farzaei F, Fotouhi M, Alavi SS, Bahramsoltani R, Naseri R, Momtaz S, Abbasabadi Z, Rahimi R, Farzaei MH, Bishayee A. Pharmacological effects of gallic acid in health and diseases: A mechanistic review. Iran J Basic Med Sci. 2019: 22: 225-37.

Karamac M, Kosiñska A, Pegg RB. Comparison of radical-scavenging activities for selected phenolic acids. Polish J Food Nutr Sci. 2005; 14: 165-70.

Kim H, Banerjee N, Barnes RC, Pfent CM, Talcott ST, Dashwood RH, Mertens-Talcott SU. Mango polyphenolics reduce inflammation in intestinal colitis-involvement of the miR-126/PI3K/AKT/mTOR axis in vitro and in vivo. Mol Carcinog. 2017; 56: 197-207.

Kim MJ, Seong AR, Yoo JY, Jin CH, Lee YH, Kim YJ, Lee J, Jun WJ, Yoon HG. Gallic acid, a histone acetyltransferase inhibitor, suppresses β-amyloid neurotoxicity by inhibiting microglial-mediated neuroinflammation. Mol Nutr Food Res. 2011; 55: 1798-808.

Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev. 2001; 81: 807-69.

Lai J, Liu Y, Liu C, Qi M, Liu R, Zhu X, Zhou Q, Chen Y, Guo A, Hu C. Indirubin inhibits LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways. Inflammation 2017; 40: 1-12.

Lim HS, Jang Y, Moon BC, Park G. NF-κB signaling contributes to the inhibitory effects of Bombyx batryticatus on neuroinflammation caused by MPTP toxicity. Bangladesh J Pharmacol. 2021; 16: 96-102.

Liu KY, Hu S, Chan BC, Wat EC, Lau CB, Hon KL, Fung KP, Leung PC, Hui PC, Lam CW, Wong CK. Anti-inflammatory and anti-allergic activities of pentaherb formula, Moutan Cortex (Danpi) and gallic acid. Molecules 2013; 18: 2483-500.

Nenadis N, Lazaridou O, Tsimidou MZ. Use of reference compounds in antioxidant activity assessment. J Agric Food Chem. 2007; 55: 5452-60.

Portugal M, Barak V, Ginsburg I, Kohen R. Interplay among oxidants, antioxidants, and cytokines in skin disorders: Present status and future considerations. Biomed Pharmacother. 2007; 61: 412-22.

Ricciarelli R, Tasinato A, Clément S, Ozer NK, Boscoboinik D, Azzi A. Alpha-tocopherol specifically inactivates cellular protein kinase C alpha by changing its phosphorylation state. Biochem J. 1998; 334: 243-49.

Sánchez-Moreno C, Larrauri JA, Saura-Calixto F. A procedure to measure the antiradical efficiency of polyphenols. J Sci Food Agric. 1998; 76: 270-76.

Sardana K, Sachdeva S. Role of nutritional supplements in selected dermatological disorders: A review. J Cosmet Dermatol. 2022; 21: 85-98.

Serrano A, Palacios C, Roy G, Cespón C, Villar ML, Nocito M, González-Porqué P. Derivatives of gallic acid induce apoptosis in tumoral cell lines and inhibit lymphocyte proliferation. Arch Biochem Biophys. 1998; 350: 49-54.

Su TR, Lin JJ, Tsai CC, Huang TK, Yang ZY, Wu MO, Zheng YQ, Su CC, Wu YJ. Inhibition of melanogenesis by gallic acid: Possible involvement of the PI3K/Akt, MEK/ERK and Wnt/β-catenin signaling pathways in B16F10 cells. Int J Mol Sci. 2013; 14: 20443-58.

Sung YY, Kim YS, Kim HK. Illicium verum extract inhibits TNF-alpha- and IFN-gamma-induced expression of chemokines and cytokines in human keratinocytes. J Ethnopharmacol. 2012; 144: 182-89.

Takada Y, Khuri FR, Aggarwal BB. Protein farnesyltransferase inhibitor (SCH 66336) abolishes NF-kappaB activation induced by various carcinogens and inflammatory stimuli lead-ing to suppression of NF-kappaB-regulated gene expression and up-regulation of apoptosis. J Biol Chem. 2004; 279: 26287-99.

Tanaka M, Sato A, Kishimoto Y, Mabashi-Asazuma H, Kondo K, Iida K. Gallic acid inhibits lipid accumulation via AMPK pathway and suppresses apoptosis and macrophage-mediated inflammation in hepatocytes. Nutrients 2020; 12: 1479.

Truzzi F, Valerii MC, Tibaldi C, Zhang Y, Abduazizova V, Spisni E, Dinelli G. Are supplements safe? Effects of gallic and ferulic acids on in vitro cell models. Nutrients 2020; 12: 1591.

Tsang MS, Jiao D, Chan BC, Hon KL, Leung PC, Lau CB, Wong EC, Cheng L, Chan CK, Lam CW, Wong CK. Anti-inflammatory activities of pentaherbs formula, berberine, gallic acid and chlorogenic acid in atopic dermatitis-like skin inflammation. Molecules 2016; 21: 519.

Wang HQ, Smart RC. Overexpression of protein kinase C-alpha in the epidermis of transgenic mice results in striking alterations in phorbol ester-induced inflammation and COX-2, MIP-2 and TNF-alpha expression but not tumor promotion. J Cell Sci. 1999; 112: 3497-506.

Yoon CH, Chung SJ, Lee SW, Park YB, Lee SK, Park MC. Gallic acid, a natural polyphenolic acid, induces apoptosis and inhibits proinflammatory gene expressions in rheumatoid arthritis fibroblast-like synoviocytes. Joint Bone Spine. 2013; 80: 274-79.

Yoshino M, Haneda M, Naruse M, Htay HH, Iwata S, Tsubouchi R, Murakami K. Prooxidant action of gallic acid compounds: Copper-dependent strand breaks and the formation of 8-hydroxy-2'-deoxyguanosine in DNA. Toxicol In Vitro 2002; 16: 705-09.

Zhou X, Chen Y, Cui L, Shi Y, Guo C. Advances in the pathogenesis of psoriasis: From keratinocyte perspective. Cell Death Dis. 2022; 13: 81.

Downloads

Published

2023-01-13

How to Cite

Shiu, P. H.-T., C. Zheng, P. . Rangsinth, W. Wang, J. Li, R. Li, and G. P.-H. Leung. “Anti-Inflammatory Effect of Gallic Acid on HaCaT Keratinocytes through the Inhibition of MAPK-, NF-KB-, and Akt-Dependent Signaling Pathways”. Bangladesh Journal of Pharmacology, vol. 18, no. 1, Jan. 2023, pp. 24-32, doi:10.3329/bjp.v18i1.63052.

Issue

Section

Research Articles