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Anti-inflammatory function of 4-tert-butylphenyl salicylate through down-regulation of the NF-kappa B pathway

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Abstract

The salicylic acid derivative 4-tert-butylphenyl salicylate (4-TBPS) possesses anti-inflammatory activity. We demonstrated this and elucidated the mechanisms involved by using the lipopolysaccharide-stimulated Raw 264.7 mouse macrophage model. The 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blot, enzyme-linked immunosorbent assay, and reverse transcriptase-polymerase chain reaction were performed to explore 4-TBPS anti-inflammatory activity. We found that 4-TBPS decreased nitric oxide production without cytotoxic effects on macrophages and reduced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in a dose-dependent manner. Additionally, mRNA expressions of iNOS and COX-2 significantly reduced, with concentrations between 1 and 15 µg/ml. Furthermore, 4-TBPS significantly inhibited the production of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin- (IL)-1β, and IL-6. Moreover, mRNA gene expression of TNF-α, IL-1β, and IL-6 was attenuated in a dose-dependent manner. 4-TBPS potently inhibited translocation of nuclear factor-κB (NF-κB) into the nucleus by degrading IκB kinase (IκBα) following its phosphorylation, thereby causing NF-κB to remain inactive. Collectively, our data indicate that 4-TBPS significantly (p < 0.01) targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, TNF-α, IL-1β, and IL-6 through downregulation of the NF-κB pathway. This indicates that 4-TBPS may have therapeutic potential in inflammatory disorders.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MEST) (2010-0029178) and “Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ01128901)” Rural Development Administration, Republic of Korea.

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    Authors and Affiliations

    1. Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, 501-759, Korea

      Yun Hee Choi, Baek Hee Na, Yoon Seok Choi, Md. Saifur Rahman, Mi Ri Kim, Jun-Pil Jee & Jin Cheol Yoo

    2. Department of Complementary & Alternative Medicine, Chosun University, Gwangju, 501-759, Korea

      Jihoon Shin

    3. Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin-si, Gyeonggi-do, Korea

      Joo Won Suh

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    1. Yun Hee Choi
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    Correspondence to Joo Won Suh or Jin Cheol Yoo.

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    Yun Hee Choi and Baek Hee Na both authors contributed equally to this work.

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    Choi, Y.H., Na, B.H., Choi, Y.S. et al. Anti-inflammatory function of 4-tert-butylphenyl salicylate through down-regulation of the NF-kappa B pathway. Arch. Pharm. Res. 39, 429–436 (2016). https://doi.org/10.1007/s12272-015-0679-3

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