Effect of Manuka Honey on Transforming Growth Factor Beta-1-Induced Extracelluar Matrix Production in Nasal Polyp Derived Fibroblasts

Abstract

Background and Objectives Manuka honey has anti-microbial, anti-inflammatory, and anti-proliferative action with a high concentration of methylglyoxal compound. It is also effective in killing Staphylococcus aureus biofilm and effective for the acute exacerbation of chronic rhinosinusitis. The aim of this study was to determine the anti-fibrotic effect of manuka honey in nasal polyp fibroblasts. Materials and Method Primary nasal fibroblasts were isolated from nasal polyps and treated with transforming growth factor-beta 1 (TGF-β1). To determine the anti-fibrotic effect of manuka honey, fibroblasts were pre-treated with various concentration of the honey. Reverse transcription-polymerase chain reaction and western blot analysis were then performed to determine α-smooth muscle actin (α-SMA), collagen type I, and matrix metalloproteinase-9 (MMP-9) messenger ribonucleic acid (mRNA) expression and protein production in nasal polyp fibroblasts. Phosphorylated Smad (pSmad) 2/3 and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) were then determined by western blotting. Results TGF-β1 stimulation increased α-SMA, collagen type I, and MMP-9 mRNA expression and protein production in nasal polyp fibroblasts. Manuka honey effectively suppressed α-SMA, collagen type I, and MMP-9 mRNA expression and protein production. Its inhibitory role on TGF-β1 induced myofibroblast differentiation and its extracellular matrix production was associated with Smad2/3 and AMPK pathway. Conclusion Manuka honey can inhibit TGF-β1 induced myofibroblast differentiation, collagen type I, and MMP-9 production in nasal fibroblasts. These results suggest that manuka honey might be a useful candidate for the inhibition of nasal polyp formation if further studies in vivo were accompanied. Korean J Otorhinolaryngol-Head Neck Surg 2019;62(6):336-42 Key Words Extracellular matrix ㆍFibroblast ㆍManuka honey ㆍNasal polyp ㆍ Transforming growth factor beta. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ylococcus aureus에 대한 항균효과 뿐 아니라 비강 세척을 통해 만성 비부비동염의 급성 악화가 있는 환자에 대한 치료 효과가 입증되어 임상적 활용 가능성이 제시되고 있다. 16,21) 본 연구를 통해 마누카꿀이 비용 섬유아세포의 근섬유모세 포 분화와 세포외기질 생성을 억제할 수 있음이 확인되었다. 향후 마누카꿀의 임상적 활용을 위해서는 생체 내 실험을 통 한 섬유화 억제 효과의 입증이 필요하며, 만성 비부비동염 발병 억제 효과와 마누카꿀의 국소 비강 치료제로의 활용 가능성을 확인하기 위한 추가적인 연구가 필요할 것이다. ORCIDSeung-Heon Shin https://orcid.org/0000-0002-9118-0590