PMID- 38373665 OWN - NLM STAT- MEDLINE DCOM- 20240315 LR - 20240315 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 326 DP - 2024 May 23 TI - Jiawei Yanghe Decoction attenuate allergic airway inflammation by suppressing group 2 innate lymphoid cells responses. PG - 117927 LID - S0378-8741(24)00226-5 [pii] LID - 10.1016/j.jep.2024.117927 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Yanghe Decoction (JWYHD) is modified Yanghe Decoction (YHD). YHD historically utilized as a potent medicinal solution for addressing chronic inflammatory conditions, holds promising therapeutic potential in the treatment of asthma. However, the mechanisms underlying JWYHD's effects on allergic asthma remain unclear. AIM OF THE STUDY: To investigate the therapeutic effect as well as the underlying mechanisms of JWYHD on asthmatic mice. MATERIALS AND METHODS: The ovalbumin (OVA)-induced mouse model was utilized, followed by the administration of JWYHD to allergic asthmatic mice. Subsequently, inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung tissues were conducted. The levels of various cytokines including interleukin (IL)-4, IL-5, IL-13, IL-33, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma in BALF, as well as the total immunoglobulin E (IgE) content in serum, were assessed. Lung function and tissue pathology examinations were performed to assess the protective impacts of JWYHD. The chemical components of JWYHD and its lung prototype compounds (referred to the chemical components present in JWYHD that were observed in the lung) were explored by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). RNA-seq analysis revealed the regulation mechanisms of JWYHD treating asthma. Furthermore, the effect of JWYHD on type 2 innate lymphoid cells (ILC2s) in asthmatic mice was detected by flow cytometry and Smart-RNA-seq analysis. Then molecular docking analysis was used to show the interaction between identified compounds and key targets. RESULTS: JWYHD significantly attenuated the airway inflammation of asthmatic mice, reduced the levels of inflammatory cells in BALF, as well the levels of the cytokines IL-4, IL-5, IL-13, IL-33, and TNF-alpha in BALF and IgE in serum. Airway hyperresponsiveness (AHR) and lung inflammation infiltration were also alleviated by JWYHD. Moreover, RNA-seq analysis revealed that JWYHD attenuated airway inflammation in asthmatic mice via regulating immunity. Flow cytometry confirmed that JWYHD could inhibit ILC2 responses. ILC2 Smart-RNA-seq analysis showed that JWYHD impaired the inflammation reaction-related signaling pathways in ILC2s, and neuropilin-1 (Nrp1), endothelial transcription factor 3 (GATA3) and interleukin 1 receptor like protein 1 (ST2) might be the key targets. The molecular docking analysis investigating the connection between the primary targets and JWYHD's prototype compounds in the lung demonstrated that liquiritin apioside, icariin, glycyrrhizic acid, and uralsaponin B, identified through UPLC-Q-TOF/MS, exhibited significant affinity in binding to the mentioned key targets. CONCLUSION: Our results suggested that the mechanism of JWYHD in treating asthma might be related to limiting ILC2 responses. Our findings provided some pharmacological evidence for the clinical application of JWYHD in the treatment of asthma. CI - Copyright (c) 2024 Elsevier B.V. All rights reserved. FAU - Wang, Yu AU - Wang Y AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Cui, Jie AU - Cui J AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Jiang, Yuwei AU - Jiang Y AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Zhang, Shaoyan AU - Zhang S AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Chen, Linjin AU - Chen L AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Ma, Zifeng AU - Ma Z AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Yang, Di AU - Yang D AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Zhang, Zhengyi AU - Zhang Z AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Huang, Xing AU - Huang X AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. FAU - Yang, Yongqing AU - Yang Y AD - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Guo, Jinglei AU - Guo J AD - Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. FAU - Lu, Zhenhui AU - Lu Z AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: Dr_luzh@shutcm.edu.cn. FAU - Li, Cui AU - Li C AD - Institute of Respiratory Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. Electronic address: lh6133@shutcm.edu.cn. LA - eng PT - Journal Article DEP - 20240217 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 0 (yanghe) RN - 0 (Interleukin-33) RN - 0 (Interleukin-13) RN - 0 (Interleukin-5) RN - 0 (Cytokines) RN - 37341-29-0 (Immunoglobulin E) RN - 9006-59-1 (Ovalbumin) RN - 0 (Drugs, Chinese Herbal) SB - IM MH - Mice MH - Animals MH - *Immunity, Innate MH - Interleukin-33 MH - Interleukin-13 MH - Interleukin-5 MH - Molecular Docking Simulation MH - Lymphocytes/metabolism MH - *Asthma MH - Lung MH - Inflammation/drug therapy/pathology MH - Cytokines/metabolism MH - Bronchoalveolar Lavage Fluid MH - Immunoglobulin E MH - Ovalbumin/pharmacology MH - Mice, Inbred BALB C MH - Disease Models, Animal MH - *Drugs, Chinese Herbal OTO - NOTNLM OT - Airway inflammation OT - Allergic asthma OT - ILC2s OT - Jiawei yanghe decoction OT - Molecular docking COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2024/02/20 11:50 MHDA- 2024/03/15 06:43 CRDT- 2024/02/19 19:17 PHST- 2023/12/29 00:00 [received] PHST- 2024/02/07 00:00 [revised] PHST- 2024/02/16 00:00 [accepted] PHST- 2024/03/15 06:43 [medline] PHST- 2024/02/20 11:50 [pubmed] PHST- 2024/02/19 19:17 [entrez] AID - S0378-8741(24)00226-5 [pii] AID - 10.1016/j.jep.2024.117927 [doi] PST - ppublish SO - J Ethnopharmacol. 2024 May 23;326:117927. doi: 10.1016/j.jep.2024.117927. Epub 2024 Feb 17.