Glycyrrhizic acid restrains airway inflammation and remodeling in asthma via the TGF‑β1/Smad signaling pathway

Abstract

The anti-inflammatory effects of glycyrrhizic acid (GA) against asthma have previously been reported; however, the underlying molecular mechanism of GA in asthma has not yet been elucidated. Thus, the present study aimed to determine the function and potential molecular mechanism of GA for modulating the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway in asthma-associated airway inflammation and remodeling. In order to study the mechanism of GA on airway inflammation and airway remodeling in asthmatic mice, a mouse model of chronic asthma was constructed. A total of 50 female mice were randomly assigned into five groups (10 mice/group), as follows: Blank group, asthma group, GA group, dexamethasone group and GA + TGF-β1 group. Hematoxylin and eosin, and Masson staining were performed to assess the airway inflammation and remodeling in mice with ovalbumin (OVA)-induced asthma. The serum levels of interleukin (IL)-4, IL-5, IL-13 and IL-17 in mice were assessed via the enzyme-linked immunosorbent assay. Reverse transcription-quantitative PCR and western blot analyses were performed to detect the levels of TGF-β1 and Smads in lung tissues of each group of mice. The results demonstrated that GA and dexamethasone treatment mitigated airway inflammation, inflammatory cell infiltration and airway remolding, with a concomitant decrease in the expression levels of IL-4, IL-5, IL-13 and IL-17, in mice with OVA-induced asthma. In addition, the levels of TGF-β1 and Smad2 notably decreased, while Smad7 expression increased in the GA and dexamethasone groups compared with the asthma group. Furthermore, histopathological morphometry exhibited significantly elevated inflammatory cell infiltration, airway wall and smooth muscle, collagen secretion and inflammatory cytokines in the serum of mice in the GA + TGF-β1 group compared with the GA group. Taken together, the results of the present study suggest that GA ameliorates airway inflammation and remodeling via the TGF-β1/Smad signaling pathway in mice with asthma.

Preparation and Characterization of a Glycyrrhizic Acid-Based Drug Delivery System for Allergen-Specific Immunotherapy

“…Tu et al reported that in the liver and spleen of murine fibrosis models, glycyrrhizin upregulated both Th1/Th2 and Treg/Th17 balances to Th1- and Treg-dominant lineages via multiple pathways such as via c-Jun amino terminal kinase, extracellular signal-regulated kinase and PI3K/AKT [ 32 ]. In another study, it was shown that GA reduced airway inflammation and remodeling via the TGF-β1/Smad signaling pathway [ 33 ]. The exact mechanism of the immune response modulating in AIT by GA is still unknown and requires further study.…”

Research progress of icariin, an extract of traditional Chinese medicine, in the treatment of asthma

“…47 Transforming growth factor-1 (TGF-β1) is the main regulator that can promote airway fibrosis and collagen deposition by regulating cytokines such as Smads proteins. 48 In the treatment of diabetic nephropathy, many benefits such as antiallergic and anti-inflammatory effects and enhancement of body fluid and cellular immunity. 62 This evidence vouches for the high safety of the clinical application of icariin and its feasibility in treating asthma, providing support for further clinical application of icariin.…”

The Role and Mechanisms of Traditional Chinese Medicine for Airway Inflammation and Remodeling in Asthma: Overview and Progress

“…ex DC., where its anti-inflammatory activity has also been proved in a past study (Yang et al, 2017). GA (Yao and Fu, 2021) can significantly alleviate airway inflammation, inflammatory cell infiltration, and remodeling in vitro and markedly restore the thickness of ASM and airway walls in vivo, which is at least partly associated with the modulation of the TGF-β1/Smad signaling pathway. It is worth noting that the study was the first to investigate that GA may suppress chronic asthma symptoms.…”