DFSG, a novel herbal cocktail with anti-asthma activity, suppressed MUC5AC in A549 cells and alleviated allergic airway hypersensitivity and inflammatory cell infiltration in a chronic asthma mouse model

Li-Jen Lin; Hui Ying Huang

doi:10.1016/j.biopha.2019.109584

DFSG, a novel herbal cocktail with anti-asthma activity, suppressed MUC5AC in A549 cells and alleviated allergic airway hypersensitivity and inflammatory cell infiltration in a chronic asthma mouse model

Biomed Pharmacother. 2020 Jan:121:109584. doi: 10.1016/j.biopha.2019.109584. Epub 2019 Nov 19.

Authors

Li-Jen Lin¹, Hui Ying Huang²

Affiliations

¹ School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung 404, Taiwan; Research Center for Chinese Herbal Medicine, China Medical University, Taichung 404, Taiwan. Electronic address: linlijen@mail.cmu.edu.tw.
² Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, 40402, Taiwan.

PMID: 31766098
DOI: 10.1016/j.biopha.2019.109584

Abstract

Aim of the study: To develop a novel anti-asthma drug. DFSG is a novel herbal cocktail composed of 4 types of herbal medicines. This study explored whether DFSG has the potential to attenuate asthma symptom severity and aimed to determine the immunomodulatory mechanism of DFSG using a chronic asthmatic mouse model induced by repeated challenges with Dermatogoides pteronyssinus (Der p).

Materials and methods: BALB/c mice were intratracheally inoculated with Der p (50 μl, 1 mg/ml) once a week for 5 weeks. In addition, 30 min before Der p challenge, the mice were orally administered 1x DFSG (1 g/kg) or 1/2x DFSG (0.5 g/kg). Three days after the final challenge, the mice were sacrificed to evaluate inflammatory cell infiltration, lung histological features, blood total IgE, and cytokine levels in pulmonary alveolar lavage fluid. Furthermore, 30 min after the addition of DFSG, caffeic acid, p-coumaric acid or chlorogenic acid to A549 cells, 10 ng/ml IL-1β was added to evaluate the effect of the drug on mucin 5AC (MUC5AC) gene expression after stimulation of A549 cells by IL-1β.

Results: DFSG significantly reduced Der p-induced airway hyperresponsiveness, bronchial inflammatory cell infiltration, and total IgE and IgG1 serum levels. Furthermore, DFSG significantly inhibited T_H2 cytokines and increased the expression of T_H1 cytokines. In addition, immunohistochemical staining demonstrated that DFSG inhibited MUC5AC expression in the bronchial epithelial cells. DFSG and a mixture of caffeic acid, p-coumaric acid, and chlorogenic acid inhibited MUC5AC gene expression in A549 cells after stimulation with IL-1β.

Conclusion: These results suggest that by regulating T_H1 and T_H2 cytokines and MUC5AC expression, DFSG exhibits anti-airway inflammatory cell infiltration and anti-hyperresponsiveness activity and inhibits specific immunity in a chronic asthmatic mouse model. Therefore, DFSG has potential for development into a drug for chronic asthma treatment.

Keywords: Asthma; Chronic asthmatic mouse model; Dermatogoides pteronyssinus; Herbal cocktail; MUC5AC.

MeSH terms

A549 Cells
Animals
Anti-Asthmatic Agents / pharmacology
Anti-Asthmatic Agents / therapeutic use*
Antigens, Dermatophagoides / toxicity
Asthma / chemically induced
Asthma / drug therapy*
Asthma / metabolism*
Cell Survival / drug effects
Cell Survival / physiology
Disease Models, Animal*
Dose-Response Relationship, Drug
Drugs, Chinese Herbal / pharmacology
Drugs, Chinese Herbal / therapeutic use*
Humans
Male
Mice
Mice, Inbred BALB C
Mucin 5AC / antagonists & inhibitors
Mucin 5AC / metabolism*
Random Allocation
Respiratory Hypersensitivity / chemically induced
Respiratory Hypersensitivity / drug therapy
Respiratory Hypersensitivity / metabolism

Substances

Anti-Asthmatic Agents
Antigens, Dermatophagoides
Drugs, Chinese Herbal
Muc5ac protein, mouse
Mucin 5AC