Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Inhibition of Proinflammatory Cytokine Generation in Lung Inflammation by the Leaves of Perilla frutescens and Its Constituents

  • Received : 2013.10.25
  • Accepted : 2013.12.16
  • Published : 2014.01.31
Download PDF
⟨ Previous Next ⟩

Abstract

This study was designed to find some potential natural products and/or constituents inhibiting proinflammatory cytokine generation in lung inflammation, since cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) are pivotal for provoking airway inflammation. In our preliminary screening procedure, the 70% ethanol extract of the leaves of Perilla frutescens (PFE) was found to clearly inhibit TNF-${\alpha}$ production in the lung at 100 mg/kg, after intranasal lipopolysaccharide treatment of mice. Based on this result, ten constituents including phenylpropanoids (allyltetramethoxybenzene, caffeic acid, dillapiole, elemicin, myristicin, nothoapiole, rosmarinic acid methyl ester, rosmarinic acid) and monoterpenes (perilla aldehyde and perilla ketone) were successfully isolated from the extract. Among them, elemicin and myristicin were found for the first time to concentration-dependently inhibit IL-$1{\beta}$-treated IL-6 production from lung alveolar epithelial cells (A549) at concentrations of $10-100{\mu}M$. These findings suggest that the phenylpropanoids including elemicin and myristicin have the potential to be new inhibitory agents against lung inflammation and they may contribute, at least in part, to the inhibitory activity of PFE on the lung inflammatory response.

Keywords

References

  1. Agbabiaka, T. B., Guo, R. and Ernst, E. (2008) Pelargonium sidoides for acute bronchitis: A systematic review and meta-analysis. Phytomedicine 15, 378-385. https://doi.org/10.1016/j.phymed.2007.11.023
  2. Al-Kassini, F. A. and Alhamad, E. H. (2013) A challenge to the seven widely believed concepts of COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 8, 21-30.
  3. Bae, K. (2000) The medicinal plants of Korea. pp 441 Kyo-Hak Pub. Co., Seoul.
  4. Bassoli, A., Borgonovo, G., Caimi, S., Scagloni, L., Morini, G., Moriello, A. S., Marzo, V. D. and Petrocelis, L. D. (2009) Taste-guided identification of high potency TRPA1 agonists from Perilla frutescens. Bioorg. Med. Chem. 17, 1636-1639. https://doi.org/10.1016/j.bmc.2008.12.057
  5. Benevides, P. J. C., Sartorelli, P. and Kato, M. J. (1999) Phenylpropanoids and neolignans from Piper regnellii. Phytochemistry 52, 339-343. https://doi.org/10.1016/S0031-9422(99)00177-6
  6. Chapman, R. W., Minnicozzi, M., Celly, C. S., Phillips, J. E., Kung, T. T., Hipkim, R. W., Fan, X., Rindgen, D., Deno, G., Bond, R., Gonsiorek, W., Billah, M. M., Fine, J. S. and Hey, J. A. (2007) A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation. J. Pharmacol. Exp. Ther. 322, 486-493. https://doi.org/10.1124/jpet.106.119040
  7. Choi, S. H., Hur, H. M., Yang, E. J., Jun, M., Park, H. J., Lee, K. B., Monn, E. and Song, K. S. (2008) ${\beta}$-Secretase (BACE1) inhibitors from Perilla frutescens var. acuta. Arch. Pharm. Res. 31, 183-187. https://doi.org/10.1007/s12272-001-1139-9
  8. Fujita, T., Funayoshi, A. and Nakayama, M. (1994) A phenylpropanoid glucoside from Perilla frutescens. Phytochemistry 37, 543-546. https://doi.org/10.1016/0031-9422(94)85096-8
  9. Guo, R., Pittler, M. H. and Ernst, E. (2006) Herbal medicines for the treatment of COPD: a systematic review. Euro. Respir. J. 28, 330-338. https://doi.org/10.1183/09031936.06.00119905
  10. Ha, T. J., Lee, J. H., Lee, M., Lee, B. W., Kwon, H. S., Park, C., Shim, K., Kim, H., Back, I. and Jang, D. S. (2012) Isolation and identification of phenolic compounds from the seeds of Perilla frutescens (L) and their inhibitory activities against ${\alpha}$-glucosidase and aldose reductase. Food Chem. 135, 1397-1403. https://doi.org/10.1016/j.foodchem.2012.05.104
  11. Jeffery, P. K. (2001) Remodeling in asthma and chronic obstructive lung disease. Am. J. Respir. Crit. Care Med. 164, S28-S38. https://doi.org/10.1164/ajrccm.164.supplement_2.2106061
  12. Ko, H. J., Jin, J. H., Kwon, O. S., Kim, J. T., Son, K. H. and Kim, H. P. (2011) Inhibition of experimental lung inflammation and bronchitis by phytoformula containing Broussonetia papyrifera and Lonicera japonica. Biomol. Ther. 19, 324-330. https://doi.org/10.4062/biomolther.2011.19.3.324
  13. Laouer, H., Meriem, E. K., Prado, S. and Baldovini, N. (2009) An antibacterial and antifungal phenylpropanoid from Carum montanum (Coss. Et Dur) Benth. Et Hook. Phytotherapy Res. 23, 1726-1730. https://doi.org/10.1002/ptr.2820
  14. Lee, S. Y., Kim, K. H., Lee, I. K., Lee, K. H., Choi, S. U. and Lee, K. R. (2012) A new flavonol glycoside from Hylomecon vernalis. Arch. Pharm. Res. 35, 415-421. https://doi.org/10.1007/s12272-012-0303-8
  15. Lim, H. J., Jin, H.-G., Woo, E. R., Lee, S. K. and Kim, H. P. (2013) The root barks of Morus alba and the flavonoid constituents inhibit airway inflammation. J. Ethnopharmacol. 149, 169-175. https://doi.org/10.1016/j.jep.2013.06.017
  16. Liu, J., Steigel, A., Reininger, E. and Bauer, R. (2000) Two new prenylated 3-benzoxepin derivatives as cyclooxygenase inhibitors from Perilla frutescens var. acuta. J. Nat. Prod. 63, 403-405. https://doi.org/10.1021/np990362o
  17. Lopes, M. N., Da Silva, M. S., Barbosa F, J. M., Ferreira, Z. S., Yoshida, M. and Gottlieb, O. R. (1986) Unusual benzofuranoid neolignans from Licaria chrysophylla. Phytochemistry 25, 2609-2612. https://doi.org/10.1016/S0031-9422(00)84519-7
  18. Makino, T., Furuta, A., Fujii, H., Nakagawa, T., Wakushima, H., Saito, K. and Kano, Y. (2001) Effect of oral treatment of Perilla frutescens and its constituents on type-I allergy in mice. Biol. Pharm. Bull. 24, 1206-1209. https://doi.org/10.1248/bpb.24.1206
  19. Matthys, H. and Funk, P. (2008) EPs 7630 improves acute bronchitic symptoms and shortens time to remission. Results of a randomized, double-blind, placebo-controlled, multicenter trial. Planta Med. 74, 686-692. https://doi.org/10.1055/s-2008-1074519
  20. Mohammad, I. and Waterman, P. G. (1985) Chemistry in the Annonaceae, xvii. phenylpropenes from Uvariodendron connivens seeds. J. Nat. Prod. 48 328-329. https://doi.org/10.1021/np50038a025
  21. Mossman, T. (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxic assays. J. Immunol. Methods 65, 55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  22. Mueller, R., Chanez, P., Campbell, A. M., Bousquet, J., Heusser, C. and Bullock, G. R. (1996) Different cytokine patterns in bronchial biopsies in asthma and chronic bronchitis. Respir. Med. 90, 79-85. https://doi.org/10.1016/S0954-6111(96)90202-4
  23. Nakazawa, T., Yasuda, T., Ueda, J. and Ohsawa, K. (2003) Antidepressant-like effects of apigenin and 2,4,5-trimethoxycinnamic acid from Perilla frutescens in the forced swimming test. Biol. Pharm. Bull. 26, 474-480. https://doi.org/10.1248/bpb.26.474
  24. Reid, D. J. and Pham, N. T. (2012) Roflumilast: a novel treatment for chronic pulmonary disease. Ann. Pharmacother. 46, 521-529. https://doi.org/10.1345/aph.1Q646
  25. Sanbongi, C., Takano, H., Osakabe, N., Sasa, N., Natsume, M., Yanagisawa, R., Inoue, K. I., Kato, Y., Osawa, T. and Yoshikawa, T. (2003) Rosmarinic acid inhibits lung injury induced by diesel exhaust particles. Free Radic. Biol. Med. 34, 1060-1069. https://doi.org/10.1016/S0891-5849(03)00040-6
  26. Sanbongi, C., Takano, H., Osakabe, N., Sasa, N., Natsume, M., Yanagisawa, R., Inoue, K., Sadakane, K., Ichinose, T. and Yoshikawa, T. (2004) Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in mouse model. Clin. Exp. Allergy 34, 971-977. https://doi.org/10.1111/j.1365-2222.2004.01979.x
  27. Sharma, M., Arnason, J. T., Burt, A. and Hudson, J. H. (2006) Echinacea extracts modulate the pattern of chemokine and cytokine secretion in rhinovirus-infected and uninfected epithelial cells. Phytother. Res. 20, 147-152. https://doi.org/10.1002/ptr.1824
  28. Shin, T. Y., Kim, S. H., Kim, S. H., Kim, Y. K., Park, H. J., Chae, B. S., Jung, H. J. and Kim, H. M. (2000) Inhibitory effect of mast cellmediated immediate-type allergic reactions in rats by Perilla frutescens. Immunopharmacol. Immunotoxicol. 22, 489-500. https://doi.org/10.3109/08923970009026007
  29. Ueda, H., Yamazaki, C. and Yamazaki, M. (2002) Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biol. Pharm. Bull. 25, 1197-1202. https://doi.org/10.1248/bpb.25.1197
  30. Woo, E, R. and Piao, M. S. (2004) Antioxidative constituents from Lycopus lucidus. Arch. Pharm. Res. 27, 173-176. https://doi.org/10.1007/BF02980102
  31. Yamamoto, H., Sakkibara, J., Nagatsu, A. and Sekiya, K. (1998) Inhibitors of arachidonate lipoxygenase from defatted perilla seed. J. Agric. Food Chem. 46, 862-865. https://doi.org/10.1021/jf970520m
  32. Zou, Y., Wang, Q. and Goeke, A. (2008) Organocatalytic multicomponent ${\alpha}$-methylenation/diels-alder reactions: a versatile route to substituted cyclohexenecarbaldehyde derivatives. Chem. Eur. J. 14, 5335-5345. https://doi.org/10.1002/chem.200800145

Cited by

  1. Ethanol Extract ofPerilla frutescensSuppresses Allergen-Specific Th2 Responses and Alleviates Airway Inflammation and Hyperreactivity in Ovalbumin-Sensitized Murine Model of Asthma vol.2015, 2015, https://doi.org/10.1155/2015/324265
  2. A novel coumarin, (+)-3′-angeloxyloxy-4′-keto-3′,4′-dihydroseselin, isolated from Bupleurum malconense (Chaihu) inhibited NF-κB activity vol.11, pp.1, 2016, https://doi.org/10.1186/s13020-016-0077-x
  3. Perilla frutescens Extracts Protects against Dextran Sulfate Sodium-Induced Murine Colitis: NF-κB, STAT3, and Nrf2 as Putative Targets vol.8, 2017, https://doi.org/10.3389/fphar.2017.00482
  4. Anti-amyloidogenic effects of Perilla frutescens var. acuta on beta-amyloid aggregation and disaggregation 2017, https://doi.org/10.1111/jfbc.12393
  5. Rosmarinic Acid Methyl Ester Inhibits LPS-Induced NO Production via Suppression of MyD88- Dependent and -Independent Pathways and Induction of HO-1 in RAW 264.7 Cells vol.21, pp.8, 2016, https://doi.org/10.3390/molecules21081083
  6. Synergistic Anti-inflammatory Effect of Rosmarinic Acid and Luteolin in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells vol.47, pp.1, 2015, https://doi.org/10.9721/KJFST.2015.47.1.119
  7. (Sandino-Groot ex Nates) Dugand - Lauraceae) vol.21, pp.2, 2018, https://doi.org/10.1080/0972060X.2018.1465856
  8. Anti-Amyloidogenic Effects of Asarone Derivatives From Perilla frutescens Leaves Against Beta-Amyloid Aggregation and Nitric Oxide Production vol.24, pp.23, 2019, https://doi.org/10.3390/molecules24234297
  9. Protective effects of myristicin against ulcerative colitis induced by acetic acid in male mice vol.31, pp.1, 2014, https://doi.org/10.1080/09540105.2020.1739626
  10. Antimicrobial, Anti-inflammatory, and Antioxidant Activities of the Wood ofMyristica fragrans vol.26, pp.1, 2014, https://doi.org/10.1080/10496475.2019.1676861
  11. Extracts of Perilla frutescens var. Acuta (Odash.) Kudo Leaves Have Antitumor Effects on Breast Cancer Cells by Suppressing YAP Activity vol.2021, pp.None, 2021, https://doi.org/10.1155/2021/5619761
  12. Variability of Polyphenolic Compounds and Biological Activities among Perilla frutescens var. crispa Genotypes vol.7, pp.10, 2014, https://doi.org/10.3390/horticulturae7100404
  13. Pharmacological and Therapeutic Potential of Myristicin: A Literature Review vol.26, pp.19, 2014, https://doi.org/10.3390/molecules26195914