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Effects of Morus alba L. and Natural Products Including Morusin on In Vivo Secretion and In Vitro Production of Airway MUC5AC Mucin

  • Lee, Hyun Jae (Department of Pharmacology, Chungnam National University School of Medicine) ;
  • Ryu, Jiho (Department of Pharmacology, Chungnam National University School of Medicine) ;
  • Park, Su Hyun (Department of Pharmacology, Chungnam National University School of Medicine) ;
  • Woo, Eun-Rhan (Department of Pharmacy, College of Pharmacy, Chosun University) ;
  • Kim, A Ryun (Department of Pharmacy, College of Pharmacy, Chosun University) ;
  • Lee, Sang Kook (Department of Pharmacy, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Kim, Yeong Shik (Department of Pharmacy, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Kim, Ju-Ock (Pulmonology Section, Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University School of Medicine) ;
  • Hong, Jang-Hee (Department of Pharmacology, Chungnam National University School of Medicine) ;
  • Lee, Choong Jae (Department of Pharmacology, Chungnam National University School of Medicine)
  • Received : 2014.02.12
  • Accepted : 2014.05.21
  • Published : 2014.08.29

Abstract

Background: It is valuable to find the potential activity of regulating the excessive mucin secretion by the compounds derived from various medicinal plants. We investigated whether aqueous extract of the root bark of Morus alba L. (AMA), kuwanon E, kuwanon G, mulberrofuran G, and morusin significantly affect the secretion and production of airway mucin using in vivo and in vitro experimental models. Methods: Effect of AMA was examined on hypersecretion of airway mucin in sulfur dioxide-induced acute bronchitis in rats. Confluent NCI-H292 cells were pretreated with ethanolic extract, kuwanon E, kuwanon G, mulberrofuran G, or morusin for 30 minutes and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 hours. The MUC5AC mucin secretion and production were measured by enzyme-linked immunosorbent assay. Results: AMA stimulated the secretion of airway mucin in sulfur dioxide-induced bronchitis rat model; aqueous extract, ethanolic extract, kuwanon E, kuwanon G, mulberrofuran G and morusin inhibited the production of MUC5AC mucin induced by PMA from NCI-H292 cells, respectively. Conclusion: These results suggest that extract of the root bark and the natural products derived from Morus alba L. can regulate the secretion and production of airway mucin and, at least in part, explains the folk use of extract of Morus alba L. as mucoregulators in diverse inflammatory pulmonary diseases.

Keywords

References

  1. Lee CJ, Paik SH, Ko KH, Kim KC. Effects of polycationic peptides on mucin release from airway goblet cells: relationship between polymer size and activity. Inflamm Res 2002;51:490-4. https://doi.org/10.1007/PL00012417
  2. Voynow JA, Rubin BK. Mucins, mucus, and sputum. Chest 2009;135:505-12. https://doi.org/10.1378/chest.08-0412
  3. Heo HJ, Lee HJ, Kim YS, Kang SS, Son KH, Seok JH, et al. Effects of baicalin and wogonin on mucin release from cultured airway epithelial cells. Phytother Res 2007;21:1130-4. https://doi.org/10.1002/ptr.2222
  4. Heo HJ, Lee SY, Lee MN, Lee HJ, Seok JH, Lee CJ. Genistein and curcumin suppress epidermal growth factor-induced MUC5AC mucin production and gene expression from human airway epithelial cells. Phytother Res 2009;23:1458-61. https://doi.org/10.1002/ptr.2801
  5. Lee HJ, Lee SY, Lee MN, Kim JH, Chang GT, Seok JH, et al. Inhibition of secretion, production and gene expression of mucin from cultured airway epithelial cells by prunetin. Phytother Res 2011;25:1196-200. https://doi.org/10.1002/ptr.3362
  6. Jang IM. Treatise on Asian herbal medicines. Seoul: Haksulpyunsu-kwan in Research Institute of Natural Products of Seoul National University; 2003.
  7. Chi YS, Jong HG, Son KH, Chang HW, Kang SS, Kim HP. Effects of naturally occurring prenylated flavonoids on enzymes metabolizing arachidonic acid: cyclooxygenases and lipoxygenases. Biochem Pharmacol 2001;62:1185-91. https://doi.org/10.1016/S0006-2952(01)00773-0
  8. Geng CA, Ma YB, Zhang XM, Yao SY, Xue DQ, Zhang RP, et al. Mulberrofuran G and isomulberrofuran G from Morus alba L.: anti-hepatitis B virus activity and mass spectrometric fragmentation. J Agric Food Chem 2012;60:8197-202. https://doi.org/10.1021/jf302639b
  9. Lee JC, Won SJ, Chao CL, Wu FL, Liu HS, Ling P, et al. Morusin induces apoptosis and suppresses NF-kappaB activity in human colorectal cancer HT-29 cells. Biochem Biophys Res Commun 2008;372:236-42. https://doi.org/10.1016/j.bbrc.2008.05.023
  10. Mihara S, Hara M, Nakamura M, Sakurawi K, Tokura K, Fujimoto M, et al. Non-peptide bombesin receptor antagonists, kuwanon G and H, isolated from mulberry. Biochem Biophys Res Commun 1995;213:594-9. https://doi.org/10.1006/bbrc.1995.2173
  11. Pon DJ, van Staden CJ, Boulet L, Rodger IW. Hyperplastic effects of aerosolized sodium metabisulfite on rat airway mucus-secretory epithelial cells. Can J Physiol Pharmacol 1994; 72:1025-30. https://doi.org/10.1139/y94-143
  12. Li JD, Dohrman AF, Gallup M, Miyata S, Gum JR, Kim YS, et al. Transcriptional activation of mucin by Pseudomonas aeruginosa lipopolysaccharide in the pathogenesis of cystic fibrosis lung disease. Proc Natl Acad Sci U S A 1997;94:967-72. https://doi.org/10.1073/pnas.94.3.967
  13. Shao MX, Ueki IF, Nadel JA. Tumor necrosis factor alphaconverting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Proc Natl Acad Sci U S A 2003;100:11618-23. https://doi.org/10.1073/pnas.1534804100
  14. Takeyama K, Dabbagh K, Lee HM, Agusti C, Lausier JA, Ueki IF, et al. Epidermal growth factor system regulates mucin production in airways. Proc Natl Acad Sci U S A 1999;96:3081-6. https://doi.org/10.1073/pnas.96.6.3081
  15. Hano Y, Fukai T, Nomura T, Uzawa J, Fukushima K. Structure of mulberrofuran I, a novel 2-arylbenzofuran derivatives from the cultivated mulberry tree (Morus bombycis Koidz). Chem Pharm Bull 1984;32:1260-3. https://doi.org/10.1248/cpb.32.1260
  16. Hano Y, Hirakura K, Nomura T, Terada S, Fukushima K. Components of root bark of morus lhou1 1. Structures of two new natural diels-alder adducts, kuwanons N and o. Planta Med 1984;50:127-30. https://doi.org/10.1055/s-2007-969649
  17. Nomura T, Fukai T, Narita T. Hypotensive constituent, kuwanon H, a new flavone derivative from the root bark of the cultivated mulberry tree (Morus alba L.). Heterocycles 1980; 14:1943-51. https://doi.org/10.3987/R-1980-12-1943
  18. Nomura T, Fukai T. Constituents of the cultivated mulberry tree. Planta Med 1981;42:79-88. https://doi.org/10.1055/s-2007-971550
  19. Burgel PR, Montani D, Danel C, Dusser DJ, Nadel JA. A morphometric study of mucins and small airway plugging in cystic fibrosis. Thorax 2007;62:153-61. https://doi.org/10.1136/thx.2006.062190
  20. Rogers DF, Barnes PJ. Treatment of airway mucus hypersecretion. Ann Med 2006;38:116-25. https://doi.org/10.1080/07853890600585795
  21. Hong DH, Petrovics G, Anderson WB, Forstner J, Forstner G. Induction of mucin gene expression in human colonic cell lines by PMA is dependent on PKC-epsilon. Am J Physiol 1999;277:G1041-7.
  22. Hewson CA, Edbrooke MR, Johnston SL. PMA induces the MUC5AC respiratory mucin in human bronchial epithelial cells, via PKC, EGF/TGF-alpha, Ras/Raf, MEK, ERK and Sp1-dependent mechanisms. J Mol Biol 2004;344:683-95. https://doi.org/10.1016/j.jmb.2004.09.059
  23. Park SJ, Kang SY, Kim NS, Kim HM. Phosphatidylinositol 3-kinase regulates PMA-induced differentiation and superoxide production in HL-60 cells. Immunopharmacol Immunotoxicol 2002;24:211-26. https://doi.org/10.1081/IPH-120003751

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