PMID- 36610671 OWN - NLM STAT- MEDLINE DCOM- 20230131 LR - 20230201 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 305 DP - 2023 Apr 6 TI - Evaluation of You-Gui-Wan critical compounds inhibiting ALOX-5 and HDC gene expression in RBL-2H3 cells using a fractional factorial design. PG - 116122 LID - S0378-8741(22)01161-8 [pii] LID - 10.1016/j.jep.2022.116122 [doi] AB - 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 muL, 2.5 mug/muL). 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-alpha, 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 beta-carotene. CI - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Chen, Po-Ting AU - Chen PT AD - Department of Biotechnology and Food Technology, Southern Taiwan University of Science and Technology, Tainan, 71005, Taiwan. Electronic address: ptchen@stust.edu.tw. FAU - Chen, Pei-Chi AU - Chen PC AD - Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, Taichung, Taiwan. Electronic address: simple48686@gmail.com. FAU - Wang, Jiu-Yao AU - Wang JY AD - Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, Taichung, Taiwan; Children's Hospital, China Medical University, Taichung, Taiwan. Electronic address: a122@mail.ncku.edu.tw. FAU - Wang, Shulhn-Der AU - Wang SD AD - School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. Electronic address: wsd917@mail.cmu.edu.tw. FAU - Lin, Li-Jen AU - Lin LJ AD - School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan. Electronic address: linlijen@mail.cmu.edu.tw. LA - eng PT - Journal Article DEP - 20230105 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (Drugs, Chinese Herbal) RN - 37341-29-0 (Immunoglobulin E) RN - 0 (you-gui-wan) RN - EC 1.3.11.34 (Alox5 protein, mouse) SB - IM MH - Animals MH - Mice MH - *Asthma/drug therapy/genetics MH - Cell Degranulation MH - *Drugs, Chinese Herbal/pharmacology/therapeutic use MH - Gene Expression MH - Immunoglobulin E MH - Mast Cells MH - *Respiratory Hypersensitivity/drug therapy OTO - NOTNLM OT - Chronic asthmatic mouse model OT - Dermatophagoides pteronyssinus OT - Inflammation OT - Traditional Chinese medicine OT - You-Gui-Wan COIS- Declaration of competing interest The authors declare no conflicts of interest in relation to this work. EDAT- 2023/01/08 06:00 MHDA- 2023/01/25 06:00 CRDT- 2023/01/07 19:15 PHST- 2022/10/09 00:00 [received] PHST- 2022/12/19 00:00 [revised] PHST- 2022/12/28 00:00 [accepted] PHST- 2023/01/08 06:00 [pubmed] PHST- 2023/01/25 06:00 [medline] PHST- 2023/01/07 19:15 [entrez] AID - S0378-8741(22)01161-8 [pii] AID - 10.1016/j.jep.2022.116122 [doi] PST - ppublish SO - J Ethnopharmacol. 2023 Apr 6;305:116122. doi: 10.1016/j.jep.2022.116122. Epub 2023 Jan 5.