DOI QR코드

DOI QR Code

Investigation of Anti-inflammatory and Anti-oxidative Activities of Lonicerae Flos, Citri Pericarpium and Violae Herba Complex (LCVC)

  • Hong Kyoung Kim (Dept. of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Daejeon University)
  • Received : 2022.09.28
  • Accepted : 2022.11.09
  • Published : 2022.12.01

Abstract

Objectives: The anti-inflammatory and anti-oxidative activities of LCVC (Lonicerae Flos, Citri Pericarpium and Violae Herba Complex) have not been fully elucidated. The purpose of this study was to investigate the mechanisms underlying these effects in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Methods: The evaluation of the anti-oxidative activity of LCVC was completed via DPPH and ABTS radical scavenging capacity, FRAP assay, measurement of polyphenol and flavonoid, assessment of ROS and NO levels in LPS-induced RAW 264.7 cells. The anti-inflammatory activity was defined by measuring the production of biomarkers (PGE2, IL-1B, IL-6 and TNF-𝛼), proteins (ERK, JNK, P38, Nrf2, Keap1, HO-1 and NQO1) and expressions of genes (iNOS, COX-2, IL-1𝛽, IL-6, TNF-𝛼, Nrf2, Keap1, HO-1 and NQO1) in LPS-induced RAW 264.7 cells. Results: LCVC have polyphenol and flavonoid contents. The results of DPPH and ABTS free radical scavenging capacity and FRAP assay showed that the anti-oxidative activity was increased. Production of ROS, NO, IL-6, TNF-𝛼, mRNA expressions of IL-1𝛽, IL-6, TNF-𝛼, Keap1, iNOS and COX-2 were decreased, and NQO1, Nrf2, and HO-1 were increased. In protein expression, JNK and Keap1 were decreased, NQO1, Nrf2 and HO-1 were increased, and no relationships were observed with the ERK and P38 by LCVC. Conclusions: These results suggest that LCVC may offer protective effects against LPS-induced inflammatory and oxidative responses through attenuating Nrf2/HO-1 pathway and MAPKs pathway. Therefore, we propose that LCVC has anti-inflammatory and anti-oxidative activities that have therapeutic potential in the treatment of inflammatory and oxidative disorders caused by the over-activation of macrophages.

Keywords

References

  1. Sirisinha, S. (2011). Insight into the mechanisms regulating immune homeostasis in health and disease. Asian Pacific Journal of Allergy and Immunology, 29(1), 1. https://pubmed.ncbi.nlm.nih.gov/21560483
  2. Travelli, C., Colombo, G., Mola, S., Genazzani, A. A. & Porta, C. (2018). NAMPT: A pleiotropic modulator of monocytes and macrophages. Pharmacological research, 135, 25-36. https://doi.org/10.1016/j.phrs.2018.06.022
  3. McInnes, I. B. & Schett, G. (2011). The pathogenesis of rheumatoid arthritis. New England Journal of Medicine, 365(23), 2205-2219. DOI: 10.1056/NEJMra1004965
  4. Kehrer, J. P. & Klotz, L. O. (2015). Free radicals and related reactive species as mediators of tissue injury and disease: implications for health. Critical reviews in toxicology, 45(9), 765-798. https://doi.org/10.3109/10408444.2015.1074159
  5. Linde, A., Mosier, D., Blecha, F. & Melgarejo, T. (2007). Innate immunity and inflammation-New frontiers in comparative cardiovascular pathology. Cardiovascular research, 73(1), 26-36. https://doi.org/10.1016/j.cardiores.2006.08.009
  6. Cho, B. O., Ryu, H. W., So, Y., Lee, C. W., Jin, C. H., Yook, H. S. & Jeong, I. Y. (2014). Anti-inflammatory effect of mangostenone F in lipopolysaccharide-stimulated RAW264. 7 macrophages by suppressing NF-κB and MAPK activation. Biomolecules & therapeutics, 22(4), 288. doi:10.4062/biomolther.2014.052
  7. Higuchi, M., Higashi, N., Taki, H. & Osawa, T. (1990). Cytolytic mechanisms of activated macrophages. Tumor necrosis factor and L-arginine-dependent mechanisms act synergistically as the major cytolytic mechanisms of activated macrophages. The Journal of Immunology, 144(4), 1425-1431. https://www.jimmunol.org/content/144/4/1425.short
  8. Mann, J. R., Backlund, M. G. & DuBois, R. N. (2005). Mechanisms of disease: Inflammatory mediators and cancer prevention. Nature clinical practice Oncology, 2(4), 202-210. https://doi.org/10.1038/ncponc0140
  9. Sadowska-Bartosz, I., Gajewska, A., Skolimowski, J., Szewczyk, R. & Bartosz, G. (2015). Nitroxides protect against peroxynitrite-induced nitration and oxidation. Free Radical Biology and Medicine, 89, 1165-1175. https://doi.org/10.1016/j.freeradbiomed.2015.11.002
  10. Guo, S., Qiu, P., Xu, G., Wu, X., Dong, P., Yang, G. & Xiao, H. (2012). Synergistic anti-inflammatory effects of nobiletin and sulforaphane in lipopolysaccharide-stimulated RAW 264.7 cells. Journal of agricultural and food chemistry, 60(9), 2157-2164. https://doi.org/10.1021/jf300129t
  11. Kim, J., Cha, Y. N. & Surh, Y. J. (2010). A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 690(1-2), 12-23. https://doi.org/10.1016/j.mrfmmm.2009.09.007
  12. Kang, K. A. & Hyun, J. W. (2017). Oxidative stress, Nrf2, and epigenetic modification contribute to anticancer drug resistance. Toxicological research, 33(1), 1-5. https://doi.org/creativecommons.org/licenses/by/3.0/ https://doi.org/10.5487/TR.2017.33.1.001
  13. Lee, T. S. & Chau, L. Y. (2002). Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nature medicine, 8(3), 240-246. https://doi.org/10.1038/nm0302-240
  14. Korean oriental medical university committee of textbook publish (2004). Herbology. Seoul. Younglimsa. http://www.yes24.com/Product/Goods/25254529
  15. Kwak, W. J., Han, C. K., Chang, H. W., Kim, H. P., Kang, S. S. & Son, K. H. (2003). Loniceroside C, an antiinflammatory saponin from Lonicera japonica. Chemical and pharmaceutical bulletin, 51(3), 333-335. https://doi.org/10.1248/cpb.51.333
  16. Kim, H. S. & Ko, K. S. (2020). Antioxidant and anti-inflammatory effects of ginseng berry ethanol extracts as a cosmetic ingredient. Asian Journal of Beauty and Cosmetology, 18(3), 389-397. http://dx.doi.org/10.20402/ajbc.2020.0052
  17. Rang, M. J. (2013). Anti-inflammatory and anti-allergic effects of herbal extracts on atopic dermatitis (Part II). Journal of the Korean Applied Science and Technology, 30(1), 173-182. https://doi.org/10.12925/jkocs.2013.30.1.173
  18. Korean oriental medical university committee of textbook publish (2004). Herbology. Seoul. Younglimsa. http://www.yes24.com/Product/Goods/25254529
  19. Chun, J. M. & Bae, J. H. (2015). Preparation of fermented citrus peels extracts for their antimicrobial activity against campylobacter jejuni. Journal of the Korean Society of Food Culture, 30(4), 475-480. https://doi.org/10.7318/KJFC/2015.30.4.475
  20. Lee, J. B., Choi, J. H., Kim, H. T., Kim, Y. K. & Yu, Y. B. (2016). Acute toxicity, Dermal and Ocular Irritation Studies of Taglisodog-eum ointment. Herbal Formula Science, 24(4), 289-300. https://doi.org/10.14374/HFS.2016.24.4.289
  21. Hink, U. & Münzel, T. (2006). COX-2, Another Important Player in the Nitric Oxide-Endothelin Cross-Talk: Good News for COX-2 Inhibitors?. Circulation research, 98(11), 1344-1346. https://doi.org/10.1161/01.RES.0000228471.38761.93
  22. Hong, M., Li, S., Tan, H. Y., Cheung, F., Wang, N., Huang, J. & Feng, Y. (2017). A network-based pharmacology study of the herb-induced liver injury potential of traditional hepatoprotective Chinese herbal medicines. Molecules, 22(4), 632. https://doi.org/10.3390/molecules22040632
  23. Shen, T., Chen, X. M., Harder, B., Long, M., Wang, X. N., Lou, H. X. & Zhang, D. D. (2014). Plant extracts of the family Lauraceae: a potential resource for chemopreventive agents that activate the nuclear factor-erythroid 2-related factor 2/antioxidant response element pathway. Planta medica, 80(05), 426-434. DOI: 10.1055/s-0034-1368197
  24. Huang, K. G. (1998). The Pharmacology of Chinese herbs. 2nd ed. Boca Ranton. CRC. 388-389. https://www.routledge.com/The-Pharmacology-of-Chinese-Herbs/Huang/p/book/9780849316654
  25. Park, C. H., Jung, H. K., Jeong, Y. S., Hong, J. H., Lee, G. D. & Park, C. D. (2011). Effects of citrus peel ethanol extract on the serum lipid and body fat of high-fat-diet-fed rats. Korean Journal of Food Preservation, 18(4), 567-574. https://doi.org/10.11002/kjfp.2011.18.4.567
  26. Choi, Y. H., Jung, S. C. & Eun, S. Y. (2010). Anti-neuroinflammatory and anti-oxidative activitives of the ethanol extract from Citrus unshiu MARC. The journal of medicine science and life science. 7(1): 88-93. https://oak.jejunu.ac.kr/handle/2020.oak/9340
  27. Mills, E. L. & O'Neill, L. A. (2016). Reprogramming mitochondrial metabolism in macrophages as an anti-inflammatory signal. European journal of immunology, 46(1), 13-21. https://doi.org/10.1002/eji.201445427
  28. Waxman, K. (1996). Shock: ischemia, reperfusion, and inflammation. New horizons (Baltimore, Md.), 4(2), 153-160. https://europepmc.org/article/med/8774791
  29. Ren, K. & Torres, R. (2009). Role of interleukin-1β during pain and inflammation. Brain research reviews, 60(1), 57-64. https://doi.org/10.1016/j.brainresrev.2008.12.020
  30. Shan, Y., Lambrecht, R. W., Donohue, S. E., Bonkovsky, H. L., Shan, Y., Lambrecht, R. W. & Bonkovsky, H. L. (2006). Role of Bach1 and Nrf2 in up-regulation of the heme oxygenase-1 gene by cobalt protoporphyrin. The FASEB Journal, 20(14), 2651-2653. https://doi.org/10.1096/fj.06-6346fje
  31. Madhu, B. P., Singh, K. P., Saminathan, M., Singh, R., Shivasharanappa, N., Sharma, A. K. & Manjunatha, V. (2016). Role of nitric oxide in the regulation of immune responses during rabies virus infection in mice. Virusdisease, 27(4), 387-399. https://doi.org/10.1007/s13337-016-0343-7
  32. Otterbein, L. E. & Choi, A. M. (2000). Heme oxygenase: colors of defense against cellular stress. American Journal of Physiology-Lung Cellular and Molecular Physiology, 279(6), L1029-L1037. https://doi.org/10.1152/ajplung.2000.279.6.L1029
  33. Tsan, M. F. (2006). Toll-like receptors, inflammation and cancer. In Seminars in cancer biology (Vol. 16, No. 1, pp. 32-37). Academic Press. https://doi.org/10.1016/j.semcancer.2005.07.004
  34. Huang, Y., Li, W., Su, Z. Y. & Kong, A. N (2015). The complexity of the Nrf2 pathway: beyond the antioxidant response. The Journal of nutritional biochemistry, 26(12), 1401-1413. https://doi.org/10.1016/j.jnutbio.2015.08.001
  35. Kobayashi, E. H., Suzuki, T., Funayama, R., Nagashima, T., Hayashi, M., Sekine, H. & Yamamoto, M. (2016). Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nature communications, 7(1), 1-14. doi:10.1038/ncomms11624 (2016).
  36. Kamei, Y., Sueyoshi, M., Hayashi, K. I., Terada, R. & Nozaki, H. (2009). The novel anti-Propionibacterium acnes compound, Sargafuran, found in the marine brown alga Sargassum macrocarpum. The Journal of antibiotics, 62(5), 259-263. https://doi.org/10.1038/ja.2009.25
  37. Thimmulappa, R. K., Scollick, C., Traore, K., Yates, M., Trush, M. A., Liby, K. T. & Biswal, S. (2006). Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochemical and biophysical research communications, 351(4), 883-889. https://doi.org/10.1016/j.bbrc.2006.10.102