Dictamnus dasycarpus Turcz. attenuates airway inflammation and mucus hypersecretion by modulating the STAT6-STAT3/FOXA2 pathway

Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved..

BACKGROUND: Effects of Dictamnus dasycarpus Turcz. on allergic asthma and their underlying mechanisms remain unclarified. Thus, we investigated the effects of D. dasycarpus Turcz. water extract (DDW) on mucus hypersecretion in mice with ovalbumin (OVA)-induced asthma and human bronchial epithelial cells.

METHODS: BALB/c mice were used to establish an OVA-induced allergic asthma model. Mice were grouped into the OVA sensitization/challenge, 100 and 300 mg/kg DDW treatment, and dexamethasone groups. In mice, cell counts in bronchoalveolar lavage fluid (BALF), serum and BALF analyses, and histopathological lung tissue analyses were performed. Furthermore, we confirmed the basic mechanism in interleukin (IL)-4/IL-13-treated human bronchial epithelial cells through western blotting.

RESULTS: In OVA-induced asthma mice, DDW treatment reduced inflammatory cell number and airway hyperresponsiveness and ameliorated histological changes (immune cell infiltration, mucus secretion, and collagen deposition) in lung tissues and serum total immunoglobulin E levels. DDW treatment lowered BALF IL-4, IL-5, and IL-13 levels; reduced levels of inflammatory mediators, such as thymus- and activation-regulated chemokine, macrophage-derived chemokine, and interferon gamma-induced protein; decreased mucin 5AC (MUC5AC) production; decreased signal transducer and activator of transcription (STAT) 6 and STAT3 expression; and restored forkhead box protein A2 (FOXA2) expression. In IL-4/IL-13-treated human bronchial epithelial cells, DDW treatment inhibited MUC5AC production, suppressed STAT6 and STAT3 expression (related to mucus hypersecretion), and increased FOXA2 expression.

CONCLUSIONS: DDW treatment modulates MUC5AC expression and mucus hypersecretion by downregulating STAT6 and STAT3 expression and upregulating FOXA2 expression. These findings provide a novel approach to manage mucus hypersecretion in asthma using DDW.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:173

Enthalten in:

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 173(2024) vom: 29. März, Seite 116319

Sprache:

Englisch

Beteiligte Personen:

Jung, Myung-A [VerfasserIn]
Lee, Joo Young [VerfasserIn]
Kim, Yu Jin [VerfasserIn]
Ji, Kon-Young [VerfasserIn]
Lee, Mi Han [VerfasserIn]
Jung, Dong Ho [VerfasserIn]
Kim, Yun Hee [VerfasserIn]
Kim, Taesoo [VerfasserIn]

Links:

Volltext

Themen:

135845-92-0
207137-56-2
9006-59-1
Asthma
Cytokines
Dictamnus dasycarpus Turcz.
FOXA2
FOXA2 protein, human
Hepatocyte Nuclear Factor 3-beta
Interleukin-13
Interleukin-4
Journal Article
MUC5AC
Ovalbumin
STAT3
STAT3 Transcription Factor
STAT3 protein, human
STAT6
STAT6 Transcription Factor
STAT6 protein, human

Anmerkungen:

Date Completed 27.03.2024

Date Revised 27.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.biopha.2024.116319

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369125479