Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Aromadendrin Inhibits Lipopolysaccharide-Induced Inflammation in BEAS-2B Cells and Lungs of Mice

  • Juhyun Lee (Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB)) ;
  • Ji-Won Park (Practical Research Division, Honam National Institute of Biological Resources (HNIBR)) ;
  • Jinseon Choi (Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB)) ;
  • Seok Han Yun (Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB)) ;
  • Bong Hyo Rhee (Department of Biology Education, Korea National University of Education) ;
  • Hyeon Jeong Jeong (Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB)) ;
  • Hyueyun Kim (Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB)) ;
  • Kihoon Lee (Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kyung-Seop Ahn (Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB)) ;
  • Hye-Gwang Jeong (College of Pharmacy, Chungnam National University) ;
  • Jae-Won Lee (Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB))
  • Received : 2024.01.24
  • Accepted : 2024.05.27
  • Published : 2024.09.01
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Abstract

Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells and IL-1β/IL-6/TNF-α levels in the bronchoalveolar lavage fluid and inducible nitric oxide synthase/cyclooxygenase-2/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of ALI mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1/ NAD(P)H quinone dehydrogenase 1 in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.

Keywords

Acknowledgement

This research was supported by grants from the KRIBB Research Initiative Program (grant No. KGM5522423), the Honam National Institute of Biological Resources (HNIBR), funded by the Ministry of Environment (MOE) of the Republic of Korea (grant no. HNIBR202302113), and the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and the Korean government (MSIT) (Grant. No. NRF-2020R1A2C2101228).

References

  1. Al-Harbi, N. O., Imam, F., Al-Harbi, M. M., Ansari, M. A., Zoheir, K. M., Korashy, H. M., Sayed-Ahmed, M. M., Attia, S. M., Shabanah, O. A. and Ahmad, S. F. (2016) Dexamethasone attenuates LPS-induced acute lung injury through inhibition of NF-κB, COX-2, and pro-inflammatory mediators. Immunol. Invest. 45, 349-369. https://doi.org/10.3109/08820139.2016.1157814
  2. Beckman, D. L., Mehta, P., Hanks, V., Rowan, W. H. and Liu, L. (2000) Effects of peroxynitrite on pulmonary edema and the oxidative state. Exp. Lung Res. 26, 349-359. https://doi.org/10.1080/019021400408308
  3. Codo Toafode, N. M., Marquardt, P., Ahyi, V., Fester, K., Spiegler, V. and Vissiennon, C. (2022) Anti-inflammatory potential of phenolic compounds isolated from Entada africana Guill. & Perr. used in the Republic of Benin. Front. Pharmacol. 13, 931240.
  4. de Oliveira, N. K. S., Almeida, M. R. S., Pontes, F. M. M., Barcelos, M. P., Silva, G. M., de Paula da Silva, C. H. T., Cruz, R. A. S. and da Silva Hage-Melim, L. I. (2021) Molecular docking, physicochemical properties, pharmacokinetics and toxicity of flavonoids present in Euterpe oleracea Martius. Curr. Comput. Aided Drug Des. 17, 589-617. https://doi.org/10.2174/1573409916666200619122803
  5. Fukunaga, K., Kohli, P., Bonnans, C., Fredenburgh, L. E. and Levy, B. D. (2005) Cyclooxygenase 2 plays a pivotal role in the resolution of acute lung injury. J. Immunol. 174, 5033-5039. https://doi.org/10.4049/jimmunol.174.8.5033
  6. Gibson, P. G., Qin, L. and Puah, S. H. (2020) COVID-19 acute respiratory distress syndrome (ARDS): clinical features and differences from typical pre-COVID-19 ARDS. Med. J. Aust. 213, 54-56. https://doi.org/10.5694/mja2.50674
  7. Giuliano, F. and Warner, T. D. (2002) Origins of prostaglandin E2: involvements of cyclooxygenase (COX)-1 and COX-2 in human and rat systems. J. Pharmacol. Exp. Ther. 303, 1001-1006. https://doi.org/10.1124/jpet.102.041244
  8. Huang, X., Xiu, H., Zhang, S. and Zhang, G. (2018) The role of macrophages in the pathogenesis of ALI/ARDS. Mediators Inflamm. 2018, 1264913.
  9. Hu, M., Yang, J. and Xu, Y. (2022) Effect of α-tocopherol in alleviating the lipopolysaccharide-induced acute lung injury via inhibiting nuclear factor kappa-B signaling pathways. Bioengineered 13, 3958-3968. https://doi.org/10.1080/21655979.2022.2031399
  10. Kang, J. K. and Hyun, C. G. (2020) 4-Hydroxy-7-methoxycoumarin inhibits inflammation in LPS-activated RAW264.7 macrophages by suppressing NF-κB and MAPK activation. Molecules 26, 4424.
  11. Kang, J. Y., Xu, M. M., Sun, Y., Ding, Z. X., Wei, Y. Y., Zhang, D. W., Wang, Y. G., Shen, J. L., Wu, H. M. and Fei, G. H. (2022) Melatonin attenuates LPS-induced pyroptosis in acute lung injury by inhibiting NLRP3-GSDMD pathway via activating Nrf2/HO-1 signaling axis. Int. Immunopharmacol. 109, 108782.
  12. Kim, K. H., Park, Y. J., Jang, H. J., Lee, S. J., Lee, S., Yun, B. S., Lee, S. W and Rho, M. C. (2020) Rugosic acid A, derived from Rosa rugosa Thunb., is novel inhibitory agent for NF-κB and IL-6/STAT3 axis in acute lung injury model. Phytother. Res. 34, 3200-3210. https://doi.org/10.1002/ptr.6767
  13. Kim, S. M., Min, J. H., Kim, J. H., Choi, J., Park, J. M., Lee, J., Goo, S. H., Oh, J. H., Kim, S. H., Chun, W., Ahn, K. S., Kang, S. and Lee, J. W. (2022a) Methyl p-hydroxycinnamate exerts anti-inflammatory effects in mouse models of lipopolysaccharide-induced ARDS. Mol. Med. Rep. 25, 37.
  14. Kim, S. M., Ryu, H. W., Kwon, O. K., Min, J. H., Park, J. M., Kim, D. Y., Oh, S. R., Lee, S. J., Ahn, K. S. and Lee, J. W. (2022b) Protective effect of Paulownia tomentosa fruits in an experimental animal model of acute lung injury. Microbiol. Biotechnol. 50, 310-318. https://doi.org/10.48022/mbl.2112.12007
  15. Kwon, O. K., Lee, J. W., Xuezhen, X., Harmalkar, D. S., Song, J. G., Park, J. W., Hwang, D., Min, J. H., Kim, J. H., Han, H. K., Jeong, H. G., Oh, S. R., Ahn, K. S. and Lee, K. (2020) DK-1108 exerts anti-inflammatory activity against phorbol 12-myristate 13-acetate-induced inflammation and protective effect against OVA-induced allergic asthma. Biomed. Pharmacother. 132, 110950.
  16. Laskin, D. L., Malaviya, R. and Laskin, J. D. (2019) Role of macrophages in acute lung injury and chronic fibrosis induced by pulmonary toxicants. Toxicol. Sci. 168, 287-301. https://doi.org/10.1093/toxsci/kfy309
  17. Lee, J. W., Kim, M. O., Song, Y. N., Min, J. H., Kim, S. M., Kang, M. J.,Oh, E. S., Lee, R. W., Jung, S., Ro, H., Lee, J. K., Ryu, H. W., Lee, D. Y. and Lee, S. U. (2022) Compound K ameliorates airway inflammation and mucus secretion through the regulation of PKC signaling in vitro and in vivo. J. Ginseng Res. 46, 496-504. https://doi.org/10.1016/j.jgr.2021.12.008
  18. Lee, J. W., Kim, N. H., Kim, J. Y., Park, J. H., Shin, S. Y., Kwon, Y. S., Lee, H. J., Kim, S. S. and Chun, W. (2013) Aromadendrin inhibits lipopolysaccharide-induced nuclear translocation of NF-κB and phosphorylation of JNK in RAW 264.7 macrophage cells. Biomol. Ther. (Seoul) 21, 216-221. https://doi.org/10.4062/biomolther.2013.023
  19. Lee, J. W., Chun, W., Kwon, O. K., Park, H. A., Lim, Y., Lee, J. H., Kim, D. Y., Kim, J. H., Lee, H. K., Ryu, H. W., Oh, S. R. and Ahn, K. S. (2018) 3,4,5-Trihydroxycinnamic acid attenuates lipopolysaccharide (LPS)-induced acute lung injury via downregulating inflammatory molecules and upregulating HO-1/AMPK activation. Int. Immunopharmacol. 64, 123-130. https://doi.org/10.1016/j.intimp.2018.08.015
  20. Lee, J. W., Chun, W., Lee, H. J., Min, J. H., Kim, S. M., Seo, J. Y., Ahn, K. S. and Oh, S. R. (2021) The role of macrophages in the development of acute and chronic inflammatory lung diseases. Cells 10, 897.
  21. Lee, Y., Rodriguez, C. and Dionne, R. A. (2005) The role of COX-2 in acute pain and the use of selective COX-2 inhibitors for acute pain relief. Curr. Pharm. Des. 11, 1737-1755. https://doi.org/10.2174/1381612053764896
  22. Liu, T., Zhang, L., Joo, D. and Sun, S. C. (2017) NF-κB signaling in inflammation. Signal Transduct. Target. Ther. 2, 17023.
  23. Lu, C. L., Zhu, W., Wang, D. M., Chen, W. L., Hu, M. M., Wang, M., Xu, X. J. and Lu, C. J. (2015) Inhibitory effects of chemical compounds isolated from the rhizome of Smilax glabra on nitric oxide and tumor necrosis factor-alpha production in lipopolysaccharide-induced RAW264.7 cell. Evid. Based Complement. Alternat. Med. 2015, 602425.
  24. Luo, L., Huang, F., Zhong, S., Ding, R., Su, J. and Li, X. (2022) Astaxanthin attenuates ferroptosis via Keap1-Nrf2/HO-1 signaling pathways in LPS-induced acute lung injury. Life Sci. 311, 121091.
  25. Manicone, A. M. (2009) Role of the pulmonary epithelium and inflammatory signals in acute lung injury. Expert Rev. Clin. Immunol. 5, 63-75. https://doi.org/10.1586/1744666X.5.1.63
  26. Mehta, S. (2005) The effects of nitric oxide in acute lung injury. Vascul. Pharmacol. 43, 390-403. https://doi.org/10.1016/j.vph.2005.08.013
  27. Meng, L., Li, L., Lu, S., Li, K., Su, Z., Wang, Y., Fan, X., Li, X. and Zhao, G. (2018) The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NFκB and PI3K/Akt/mTOR pathways. Mol. Immunol. 94, 7-17. https://doi.org/10.1016/j.molimm.2017.12.008
  28. Min, J. H., Kim, S. M., Park, J. W., Kwon, N. H., Goo, S. H., Ngatinem., Ningsih, S., Paik, J. H., Choi, S., Oh, S. R., Han, S. B., Ahn, K. S. and Lee, J. W. (2021) Lagerstroemia ovalifolia exerts anti- inflammatory effects in mice of LPS-induced ALI via downregulating of MAPK and NF-κB activation. J. Microbiol. Biotechnol. 31, 1501-1507. https://doi.org/10.4014/jmb.2107.07023
  29. Mokra, D. (2020) Acute lung injury - from pathophysiology to treatment. Physiol. Res. 69, S353-S366.
  30. Numata, M., Suzuki, S., Miyazawa, N., Miyashita, A., Nagashima, Y., Inoue, S., Kaneko, T. and Okubo, T. (1998) Inhibition of inducible nitric oxide synthase prevents LPS-induced acute lung injury in dogs. J. Immunol. 160, 3031-3037. https://doi.org/10.4049/jimmunol.160.6.3031
  31. Park, J. W., Park, J. M., Eum, S., Kim, J. H., Oh, J. H., Choi, J., Bach, T. T., Shin, N. V., Choi, S., Ahn, K. S. and Lee, J. W. (2022) Ficus vasculosa Wall. ex Miq. inhibits the LPS-induced inflammation in RAW264.7 macrophages. Microbiol. Biotechnol. 50, 574-583.
  32. Park, J. W., Ryu, H. W., Ahn, H. I., Min, J. H., Kim, S. M., Kim, M. G., Kwon, O. K., Hwang, D., Kim, S. Y., Choi, S., Zamora, N., Rosales, K., Oh, S. R., Lee, J. W. and Ahn, K. S. (2020) The anti-inflammatory effect of Trichilia martiana C. DC. in the lipopolysaccharidestimulated inflammatory response in macrophages and airway epithelial cells and in LPS-challenged mice. J. Microbiol. Biotechnol. 28, 1614-1625.
  33. Peng, J., Wei, D., Fu, Z., Li, D., Tan, Y., Xu, T., Zhou, J. and Zhang, T. (2015) Punicalagin ameliorates lipopolysaccharide-induced acute respiratory distress syndrome in mice. Inflammation 38, 493-499. https://doi.org/10.1007/s10753-014-9955-5
  34. Rahman, M. S., Alam, M. B., Kim, Y. K., Madina, M. H., Fliss, I., Lee, S. H. and Yoo, J. C. (2021) Activation of Nrf2/HO-1 by peptide YD1 attenuates inflammatory symptoms through suppression of TLR4/MYyD88/NF-κB signaling cascade. Int. J. Mol. Sci. 13, 5161.
  35. Song, D., Zhao, M., Feng, L., Wang, P., Li, Y. and Li, W. (2021) Salidroside attenuates acute lung injury via inhibition of inflammatory cytokine production. Biomed. Pharmacother. 142, 111949.
  36. Venditti, A., Serrilli, A. M., Rizza, L., Frasca, G., Cardile, V., Bonina, F. P. and Bianco, A. (2013) Aromadendrine, a new component of the flavonoid pattern of Olea europaea L. and its anti-inflammatory activity. Nat. Prod. Res. 27, 340-349. https://doi.org/10.1080/14786419.2012.693924
  37. Wu, H., Zhao, G., Jiang, K., Chen, X., Zhu, Z., Qiu, C., Li, C. and Deng, G. (2016) Plantamajoside ameliorates lipopolysaccharide-induced acute lung injury via suppressing NF-κB and MAPK activation. Int. Immunopharmacol. 35, 315-322. https://doi.org/10.1016/j.intimp.2016.04.013
  38. Xu, J., Zhao, S., Zhao, L. and Sun, M. (2022) Carvedilol alleviates lipopolysaccharide (LPS)-induced acute lung injury by inhibiting Ras homolog family member A (RhoA)/ROCK activities. Bioengineered 13, 4137-4145. https://doi.org/10.1080/21655979.2021.2011013
  39. Yang, L., Chen, H., Hu, Q., Liu, L., Yuan, Y., Zhang, C., Tang, J. and Shen, X. (2022) Eupalinolide B attenuates lipopolysaccharide-induced acute lung injury through inhibition of NF-κB and MAPKs signaling by targeting TAK1 protein. Int. Immunopharmacol. 111, 109148.
  40. Zhang, Y., Yan, G., Sun, C., Li, H., Fu, Y. and Xu, W. (2018) Apoptosis effects of dihydrokaempferol isolated from Bauhinia championii on synoviocytes. Evid. Based Complement. Alternat. Med. 2018, 9806160.