Evaluation of You-Gui-Wan critical compounds inhibiting ALOX-5 and HDC gene expression in RBL-2H3 cells using a fractional factorial design. (6th April 2023)

• Record Type: Journal Article
• Authors: Chen, Po-Ting; Chen, Pei-Chi; Wang, Jiu-Yao; Wang, Shulhn-Der; Lin, Li-Jen
• Is Part Of: Journal of ethnopharmacology. Volume 305(2023)
• Publication Date: 2023-04-06
• Subjects: Traditional Chinese medicine -- You-Gui-Wan -- Chronic asthmatic mouse model -- Dermatophagoides pteronyssinus -- Inflammation; ALOX-5 Arachidonate 5-lipoxygenase -- ASHMI antiasthma simplified herbal medicine intervention -- cys-LTs Cysteinyl-leukotrienes -- Dex dexamethasone -- DNP-BSA DNP-conjugated bovine serum albumin -- DNP-IgE mouse monoclonal anti-dinitrophenyl IgE -- ELISA enzyme-linked immunosorbent assay -- FBS foetal bovine serum -- FEV1 forced expiratory volume in 1 s -- FFD fractional factorial design -- GABAAR γ-aminobutyric acid type A receptor -- GMP good manufacturing practice -- HDC histidine decarboxylase -- Ig E immunoglobulin E -- IL interleukin -- i.t. intratracheal -- LTC4 Leukotriene C4 -- LTRA Leukotriene receptor antagonist -- MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) -- PGD2 Prostaglandin D2 -- P.S Penicillin/Streptomycin -- TCM Traditional Chinese medicine -- Th1 type 1 T helper cell -- Th2 type 2 T helper cell; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.116122
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: The traditional Chinese medicine (TCM) You-Gui-Wan (YGW) has been used to treat asthma for hundreds of years. Aim of the study: YGW is composed of 10 types of medicinal materials. However, the immune mechanism of YGW in asthma treatment has not been elucidated. Therefore, this study investigated asthma symptoms attenuated by YGW and the underlying immune regulatory mechanism. Materials and methods: Intratracheal (i.t.) stimulation of BALB/c mice with Dermatophagoides pteronyssinus (Der p) was performed once per week (40 μL, 2.5 μg/μL). For six consecutive weeks, different doses of YGW (0.2 g/kg and 0.5 g/kg) were orally administered 30 min before stimulation with Der p. After the last stimulation, airway hyperreactivity, lung gene expression, and total immunoglobulin E (IgE) in blood were evaluated using a whole-body plethysmograph system, real-time PCR, and ELISA, respectively. In addition, DNP-IgE/DNP-BSA was added to stimulate mast cells (RBL-2H3), and YGW or various compound compositions (Trial) were added to RBL-2H3 cells for 30 min to evaluate the effects of the drug on mast cell degranulation and on gene expression. JMP 5.1 software was used to design and analyze YGW's critical compounds by which it inhibited ALOX-5 and HDC gene expression in RBL-2H3 cells. Results: YGW significantly decreased serum total IgE levels and airway hyperresponsiveness in asthmatic mice. YGW also reduced the gene expression of IL-6, TNF-α, IL-4, IL-13, and COX-2 in the lungs of asthmatic mice and RBL-2H3 cells. YGW and the compound (Trial 21) present in YGW inhibited the gene expression of ALOX-5 and HDC in RBL-2H3 cells. Conclusion: The experimental results indicate that YGW exhibits anti-airway hyperresponsiveness and specific immunomodulatory effects. In addition, YGW synergistically inhibits ALOX-5 and HDC gene expression in mast cells through a combination of 21 compounds, including luteolin, quercetin, and β-carotene. Graphical abstract: Image 1 Highlights: You-Gui-Wan extract decreased Der p - induced airway hyperresponsiveness and total serum IgE levels in a mouse model of chronic asthma. You-Gui -Wan extract inhibited the gene expression of IL-6, TNF-α, IL-4, IL-13 and COX-2 in the lungs of asthmatic mice and RBL-2H3 cells. You-Gui -Wan extract and the compounds (Trail 21) contained in You-Gui -Wan inhibited the gene expression of ALOX-5 and HDC in RBL-2H3 cells.