Effects of Baicalein, Berberine, Curcumin and Hesperidin on Mucin Release from Airway Goblet Cells

Abstract

Baicalein, berberine, curcumin and hesperidin are the major components derived from Scutellaria baicalensis, Coptis japonica, Curcuma longa and Poncirus trifoliata, respectively. These plants have been used for the treatment of diverse chronic inflammatory diseases including respiratory disease in oriental medicine and their respective major components were reported to have various biological effects including anti-inflammatory activity. In the present study, we investigated whether these four natural products affect mucin release from airway goblet cells and compared the possible activities of these agents with the inhibitory action on mucin release by PLL and the stimulatory action by ATP. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled using ³ H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on ³ H-mucin release. The results were as follows: (i) baicalein did not affect mucin release significantly; (ii) berberine, curcumin and hesperidin increased mucin release at the highest concentration (10 ^{- 4} M); (iii) PLL inhibited and ATP increased mucin release. We conclude that berberine, curcumin and hesperidin can increase mucin release by directly acting on airway mucin-secreting cells and suggest that these agents be further studied for possible use as mild expectorants during the treatment of chronic airway diseases.

Abbreviations

PLL:poly-L-lysine

ATP:adenosine triphosphate

HTSE:hamster tracheal surface epithelial

DMSO:dimethylsulfoxide

IL-12:interleukin-12

PBS:phosphate-buffered saline

Key words

Airway - mucin - baicalein - berberine - curcumin - hesperidin

References

• 1 Newhouse M T, Biennenstock J. Respiratory tract defense mechanism. Baum GL, Wolinsky E, editors Textbook of pulmonary disease. 3rd edn Boston, Massachusetts; Little Brown and Company 1983
• 2 Ellis E F. Asthma in childhood.  J Allergy Clin Immunol. 1985;  72 (suppl) 526-39
• 3 Mutschler E, Derendorf H. Drug actions. Boca Raton, Florida; CRC Press 1995: pp. 410-1
• 4 Kim K C, McCracken K, Lee B C, Shin C Y, Jo M J, Lee C J, Ko K H. Airway goblet cell mucin: its structure and regulation of secretion.  Eur Respir J. 1997;  10 2644-9
• 5 Wasano K, Kim K C, Niles R M, Brody J S. Membrane differentiation markers of airway epithelial secretory cells.  J Histochem Cytochem. 1988;  36 167-78
• 6 Hong T, Jin G B, Cho S, Cyong J C. Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodium-induced colitis in mice.  Planta Med. 2002;  68 268-71
• 7 Brouet I, Ohshima H. Curcumin, an anti-tumour promoter and anti-inflammatory agent, inhibits induction of nitric oxide synthase in activated macrophages.  Biochem Biophys Res Commun. 1995;  206 533-40
• 8 Fukuda K, Hibiya Y, Mutoh M, Koshiji M, Akao S, Fujiwara H. Inhibition of activator protein 1 activity by berberine in human hepatoma cells.  Planta Med. 1999;  65 381-3
• 9 Lim G P, Chu T, Yang F, Beech W, Frautschy S A, Cole G M. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse.  J Neurosci. 2001;  21 8370-7
• 10 Crespo M E, Galvez J, Cruz T, Ocete M A, Zarzuelo A. Anti-inflammatory activity of diosmin and hesperidin in rat colitis induced by TNBS.  Planta Med. 1999;  65 651-3
• 11 Ko K H, Lee C J, Shin C Y, Jo M, Kim K C. Inhibition of mucin release from airway goblet cells by polycationic peptides.  Am J Physiol. 1999;  277 L811-5
• 12 Kim K C, Wasano K, Niles R M, Schuster J E, Stone P J, Brody J S. Human neutrophil elastase releases cell surface mucins from primary cultures of hamster tracheal epithelial cells.  Proc Natl Acad Sci USA. 1987;  84 9304-8
• 13 Kim K C, Rearick J I, Nettesheim P, Jetten A M. Biochemical characterization of mucous glycoproteins synthesized and secreted by hamster tracheal epithelial cells in primary culture.  J Biol Chem. 1985;  260 4021-7
• 14 Nakajima T, Imanishi M, Yamamoto K, Cyong J C, Hirai K. Inhibitory effect of baicalein, a flavonoid in Scutellaria root, on eotaxin production by human dermal fibroblasts.  Planta Med. 2001;  67 132-5
• 15 Ko W H, Law W W, Yip W C, Yue G G, Lau C W, Chen Z Y, Huang Y. Stimulation of chloride secretion by baicalein in isolated rat distal colon.  Am J Physiol. 2002;  282 G508-18
• 16 Kang B Y, Chung S W, Cho D, Kim T S. Involvement of p38 mitogen-activated protein kinase in the induction of interleukin-12 p40 production in mouse macrophages by berberine, a benzodioxoloquinolizine alkaloid.  Biochem Pharmacol. 2002;  63 1901-10
• 17 Satoskar R R, Shah S J, Shenoy S G. Evaluation of anti-inflammatory property of curcumin (diferuloylmethane) in patients with postoperative inflammation.  Int J Pharmacol Ther Toxicol. 1986;  24 651-4
• 18 Chan M M, Huang H I, Fenton M R, Fong D. In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties.  Biochem Pharmacol. 1998;  55 1955-62
• 19 llek B, Fischer H. Flavonoids stimulate Cl conductance of human airway epithelium in vitro and in vivo .  Am J Physiol. 1998;  275 L902-10