Nasal irrigation with licorice extract (Glycyrrhiza glabra) in treating nasal polyps by reducing fibroblast differentiation and extracellular matrix production in TGF-β1-stimulated nasal polyp-derived fibroblasts by inhibiting the MAPK/ERK-1/2 pathway - an in vitro and in clinic study

用甘草提取物 (Glycyrrhiza glabra) 进行鼻腔冲洗可治疗鼻息肉,方法是抑制 MAPK/ERK-1/2 通路,减少 TGF-β1 刺激的鼻息肉衍生成纤维细胞中的成纤维细胞分化和细胞外基质产生 - 一项体外和临床研究

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作者:Geng-He Chang, Pei-Rung Yang, Yu-Ching Cheng, Ke-Hsin Hsu, Ching-Yuan Wu, Yao-Hsu Yang, Yu-Shih Lin, Cheng-Ming Hsu, Ming-Shao Tsai, Yao-Te Tsai, Pey-Jium Chang

Background

To date, treating nasal polyps (NPs) is still a medical challenge. However, we have developed an innovative therapy using licorice extract (LE: Glycyrrhiza glabra) to treat rhinitis and sinusitis via nasal irrigation and have discovered that it significantly affects treatment of NPs. Hypothesis/

Conclusion

LE is clinically used to treat sinusitis with NPs through nasal irrigation, which significantly reduces the size of NPs. This effect could attenuate fibroblast differentiation, ECM production and cell migration, and one of the functional mechanisms may be through inhibition of the MAPK/ERK-1/2 signaling pathway.

Methods

The TGF-β1-stimulated NPDF model was used to examine the effect of LE on fibroblast differentiation (biomarker: α-SMA), the consequent production of extracellular matrix (ECM; biomarkers: fibronectin, FBN), and the functional signaling pathway.

Purpose

This study investigated the mechanism of LE on NPs. Study design: NPs were collected from three patients using tissue biopsies before and 2 weeks after nasal irrigation with licorice for histopathological analysis. Additionally, NPs from two patients were collected, and nasal polyp-derived fibroblasts (NPDF) were isolated and cultured.

Results

Immunohistochemistry (IHC) revealed that the number of eosinophils and the expression of α-SMA and interstitial collagen of polyps after licorice treatment significantly decreased. Additionally, RT-PCR, western blotting, and immunofluorescence (IF) showed that α-SMA and FBN expressions were significantly increased in the NPDF, which was stimulated by TGF-β1, and LE dose-dependently could effectively reduce this effect. Furthermore, western blotting showed that LE could attenuate α-SMA and FBN expressions by preventing the signaling pathway of MAPK/ERK-1/2, which IHC and IF further confirmed. In addition, LE effectively suppressed the cell migration of NPDF, which is related to polyp expansion.

Trial registration

ISRCTN (No. 51425529) registered on 17/04/2020 (retrospectively registered) - http://www.isrctn.com/ISRCTN51425529.

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