Journal of Food and Nutrition Research
ISSN (Print): 2333-1119 ISSN (Online): 2333-1240 Website: Editor-in-chief: Prabhat Kumar Mandal
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Journal of Food and Nutrition Research. 2018, 6(4), 227-233
DOI: 10.12691/jfnr-6-4-4
Open AccessArticle

Anti-Inflammatory Effect of o-Vanillic Acid on Lipopolysaccharide-Stimulated Macrophages and Inflammation Models

Jun-Kyoung Lee1, Soyoung Lee2, Tae-Yong Shin3, Dongwoo Khang4, and Sang-Hyun Kim1,

1Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea

2Immunoregulatory Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Republic of Korea

3College of Pharmacy, Woosuk University, Jeonju, Republic of Korea

4Department of Molecular Medicine, School of Medicine, Gachon University, Incheon, Republic of Korea

Pub. Date: April 24, 2018

Cite this paper:
Jun-Kyoung Lee, Soyoung Lee, Tae-Yong Shin, Dongwoo Khang and Sang-Hyun Kim. Anti-Inflammatory Effect of o-Vanillic Acid on Lipopolysaccharide-Stimulated Macrophages and Inflammation Models. Journal of Food and Nutrition Research. 2018; 6(4):227-233. doi: 10.12691/jfnr-6-4-4


Inflammation is an important biological reaction in the body in response to external stimuli. Excessive inflammation causes various inflammatory disorders such as allergic hypersensitivity, autoimmune disease, rheumatoid arthritis, and cancer. Macrophages play a major role in the inflammatory response by producing inflammatory mediators such as nitric oxide, prostaglandin E2, and pro-inflammatory cytokines. Natural products are often a source of bioactive compounds, which have great potential as novel therapeutic agents. Amomum xanthoides extract has been shown to possess various pharmacological activities including anti-inflammatory activity. This study evaluated the anti-inflammatory potential of o-vanillic acid (o-VA), a major compound in A. xanthoides, using lipopolysaccharide (LPS)-induced macrophages and in vivo animal models. o-VA decreased, in a concentration-dependent manner, the LPS-induced gene expression and production of inflammatory mediators, such as inducible nitric oxidase/cyclooxygenase-2 and pro-inflammatory cytokines, by reducing the nuclear factor-κB activation. In addition, o-VA dose-dependently ameliorated acetic acid-induced vascular permeability and zymosan-induced leukocyte migration. Thus, we suggest that o-VA can be used as a pharmacological agent or food supplement in the treatment of inflammatory conditions.

anti-inflammation o-vanillic acid macrophages pro-inflammatory cytokines

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[1]  Freire, M.O. and T.E. Van Dyke, “Natural resolution of inflammation”. Periodontol 2000, 63 (1): 149-64, Oct 2013.
[2]  Ha, H., B. Debnath, and N. Neamati, “Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases”. Theranostics, 7 (6): 1543-88, 2017.
[3]  Yamaki, K., et al., “An improved method for measuring vascular permeability in rat and mouse skin”. J Pharmacol Toxicol Methods, 48 (2): 81-6, Sep-Oct 2002.
[4]  Kuriakose, S.M., R. Singh, and J.E. Uzonna, “Host Intracellular Signaling Events and Pro-inflammatory Cytokine Production in African Trypanosomiasis”. Front Immunol, 7: 181, 2016.
[5]  Wink, D.A., et al., “Nitric oxide and redox mechanisms in the immune response”. J Leukoc Biol, 89 (6): 873-91, Jun 2011.
[6]  Forstermann, U. and W.C. Sessa, “Nitric oxide synthases: regulation and function”. Eur Heart J, 33 (7): 829-37, Apr 2012.
[7]  Arango Duque, G. and A. Descoteaux, “Macrophage cytokines: involvement in immunity and infectious diseases”. Front Immunol, 5: 491, 2014.
[8]  Klampfer, L., “Cytokines, inflammation and colon cancer”. Curr Cancer Drug Targets, 11 (4): 451-64, May 2011.
[9]  Soares-Bezerra, R.J., et al., “Natural Products as a Source for New Anti-Inflammatory and Analgesic Compounds through the Inhibition of Purinergic P2X Receptors”. Pharmaceuticals (Basel), 6 (5): 650-8, Apr 29 2013.
[10]  Ramana, K.V., S.S. Singhal, and A.B. Reddy, “Therapeutic potential of natural pharmacological agents in the treatment of human diseases”. Biomed Res Int, 2014: 573452, 2014.
[11]  Wang, J.H., et al., “Hepatoprotective effect of Amomum xanthoides against dimethylnitrosamine-induced sub-chronic liver injury in a rat model”. Pharm Biol, 51 (7): 930-5, Jul 2013.
[12]  Lee, S.B., et al., “Ethyl Acetate Fraction of Amomum xanthioides Exerts Antihepatofibrotic Actions via the Regulation of Fibrogenic Cytokines in a Dimethylnitrosamine-Induced Rat Model”. Evid Based Complement Alternat Med, 2016: 6014380, 2016.
[13]  Choi, H.G., et al., “Anti-allergic inflammatory activities of compounds of amomi fructus”. Nat Prod Commun, 10 (4): 631-2, Apr 2015.
[14]  Je, I.G., et al., “Inhibitory effect of 1,2,4,5-tetramethoxybenzene on mast cell-mediated allergic inflammation through suppression of IkappaB kinase complex”. Toxicol Appl Pharmacol, 287 (2): 119-27, Sep 2015.
[15]  Choi, E.J., et al., “Eupatilin inhibits lipopolysaccharide-induced expression of inflammatory mediators in macrophages”. Life Sci, 88 (25-26): 1121-6, Jun 2011.
[16]  Kim, M.S., et al., “Gallotannin isolated from Euphorbia species, 1,2,6-tri-O-galloyl-beta-D-allose, decreases nitric oxide production through inhibition of nuclear factor-kappa>B and downstream inducible nitric oxide synthase expression in macrophages”. Biol Pharm Bull, 32 (6): 1053-6, Jun 2009.
[17]  Je, I.G., et al., “SG-HQ2 inhibits mast cell-mediated allergic inflammation through suppression of histamine release and pro-inflammatory cytokines”. Exp Biol Med (Maywood), 240 (5): 631-8, May 2015.
[18]  Whittle, B.A., “The Use of Changes in Capillary Permeability in Mice to Distinguish between Narcotic and Nonnarcotic Alalgesics”. Br J Pharmacol Chemother, 22: 246-53, Apr 1964.
[19]  Doherty, N.S., et al., “Intraperitoneal injection of zymosan in mice induces pain, inflammation and the synthesis of peptidoleukotrienes and prostaglandin E2”. Prostaglandins, 30 (5): 769-89, Nov 1985.
[20]  Yang, G., et al., “Inhibition of lipopolysaccharide-induced nitric oxide and prostaglandin E2 production by chloroform fraction of Cudrania tricuspidata in RAW 264.7 macrophages”. BMC Complement Altern Med, 12: 250, Dec 2012.
[21]  Kroes, B.H., et al., “Anti-inflammatory activity of gallic acid”. Planta Med, 58 (6): 499-504, Dec 1992.
[22]  Lawrence, T., “The nuclear factor NF-kappaB pathway in inflammation”. Cold Spring Harb Perspect Biol, 1 (6): a001651, Dec 2009.
[23]  Coura, C.O., et al., “Mechanisms involved in the anti-inflammatory action of a polysulfated fraction from Gracilaria cornea in rats”. PLoS One, 10 (3): e0119319, 2015.
[24]  Yong, Y.K., et al., “Suppressions of serotonin-induced increased vascular permeability and leukocyte infiltration by Bixa orellana leaf extract”. Biomed Res Int, 2013: 463145, 2013.
[25]  Nourshargh, S. and R. Alon, “Leukocyte migration into inflamed tissues”. Immunity, 41 (5): 694-707, Nov 2014.
[26]  Ching, F.P., et al., “Antiinflammatory Activity of Aqueous Extract of Stereospermum kunthianum (Cham, Sandrine Petit) Stem Bark in Rats”. Indian J Pharm Sci, 71 (1): 106-10, Jan 2009.
[27]  Wang, W.Y., et al., “Role of pro-inflammatory cytokines released from microglia in Alzheimer's disease”. Ann Transl Med, 3 (10): 136, Jun 2015.
[28]  Aprioku, J.S., “Pharmacology of free radicals and the impact of reactive oxygen species on the testis”. J Reprod Infertil, 14 (4): 158-72, Oct 2013.
[29]  Soleimanpour, M., et al., “The Role of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in the Treatment of Patients With Hepatic Disease: A Review Article”. Anesth Pain Med, 6 (4): e37822, Aug 2016.
[30]  Wojdasiewicz, P., L.A. Poniatowski, and D. Szukiewicz, “The role of inflammatory and anti-inflammatory cytokines in the pathogenesis of osteoarthritis”. Mediators Inflamm, 2014: 561459, 2014.
[31]  Prado, C.M., M.A. Martins, and I.F. Tiberio, “Nitric oxide in asthma physiopathology”. ISRN Allergy, 2011: 832560, 2011.
[32]  Asiimwe, N., et al., “Nitric Oxide: Exploring the Contextual Link with Alzheimer's Disease”. Oxid Med Cell Longev, 2016: 7205747, 2016.
[33]  Kalinski, P., “Regulation of immune responses by prostaglandin E2”. J Immunol, 188 (1): 21-8, Jan 2012.
[34]  Ricciotti, E. and G.A. FitzGerald, “Prostaglandins and inflammation”. Arterioscler Thromb Vasc Biol, 31 (5): 986-1000, May 2011.
[35]  Fujiwara, N. and K. Kobayashi, “Macrophages in inflammation”. Curr Drug Targets Inflamm Allergy, 4 (3): 281-6, Jun 2005.
[36]  Justo, O.R., et al., “Evaluation of in vitro anti-inflammatory effects of crude ginger and rosemary extracts obtained through supercritical CO2 extraction on macrophage and tumor cell line: the influence of vehicle type”. BMC Complement Altern Med, 15: 390, Oct 2015.
[37]  Zhang, J.M. and J. An, “Cytokines, inflammation, and pain”. Int Anesthesiol Clin, 45 (2): 27-37, Spring 2007.
[38]  Hoesel, B. and J.A. Schmid, “The complexity of NF-kappaB signaling in inflammation and cancer”. Mol Cancer, 12: 86, Aug 2013.
[39]  Radu, M. and J. Chernoff, “An in vivo assay to test blood vessel permeability”. J Vis Exp, (73): e50062, Mar 2013.
[40]  Johnston, M.G., J.B. Hay, and H.Z. Movat, “The modulation of enhanced vascular permeability by prostaglandins through alterations in blood flow (hyperemia)”. Agents Actions, 6 (6): 705-11, Nov 1976.
[41]  Cekici, A., et al., “Inflammatory and immune pathways in the pathogenesis of periodontal disease”. Periodontol 2000, 64 (1): 57-80, Feb 2014.
[42]  Wang, H.L. and T.W. Lai, “Optimization of Evans blue quantitation in limited rat tissue samples”. Sci Rep, 4: 6588, Oct 2014.
[43]  Tatiya, A.U., et al., “Evaluation of analgesic and anti-inflammatory activity of Bridelia retusa (Spreng) bark”. J Tradit Complement Med, 7 (4): 441-51, Oct 2017.
[44]  Cash, J.L., G.E. White, and D.R. Greaves, “Chapter 17. Zymosan-induced peritonitis as a simple experimental system for the study of inflammation”. Methods Enzymol, 461: 379-96, 2009.
[45]  Leite, J.A., et al., “Ouabain Modulates Zymosan-Induced Peritonitis in Mice”. Mediators Inflamm, 2015: 265798, 2015.