PMID- 37460031 OWN - NLM STAT- MEDLINE DCOM- 20230918 LR - 20230918 IS - 1872-7573 (Electronic) IS - 0378-8741 (Linking) VI - 318 IP - Pt A DP - 2024 Jan 10 TI - Effects of total alkaloids from Alstonia scholaris (L.) R. Br. on ovalbumin-induced asthma mice. PG - 116887 LID - S0378-8741(23)00755-9 [pii] LID - 10.1016/j.jep.2023.116887 [doi] AB - ETHNOPHARMACOLOGICAL RELEVANCE: More than 300 million people worldwide suffer from asthma, a chronic respiratory inflammatory disease. Total alkaloids (TA) were extracted from the ethnic medicinal plant Alstonia solaris (L.) R.Br., which is used to treat respiratory diseases. They may be effective drugs for treating asthma, but research is still needed to determine their effectiveness and mechanism in treating asthma. AIM OF THE STUDY: To further understand TA's role in the treatment of asthma and to support the phase II trial of the drug. MATERIALS AND METHODS: In this study, we investigated the effects of TA in a mouse asthma model produced by Ovalbumin (OVA). H&E and PAS staining were used to observe the histopathological features of lung. airway hyperresponsiveness (AHR) was detected by ventilator; The expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and E-cadherin in the lungs was evaluated by IHC. The concentrations of Mucin5AC (MUC5AC), eotaxin, IL-4, IL-5, IL-9, IL-13, interferon (IFN)-gamma, IL-6, IL-8, IL-17A, IL-33, IL-25, thymic stromal lymphopoietin (TSLP), monocyte chemoattractant protein 1 (MCP-1), leukotriene (LT) B(4), LTC(4), LTD(4), LTE(4) in bronchoalveolar lavage fluid (BALF) and total IgE (tIgE), OVA-Specific IgE (OVA-IgE) in serum were measured by ELISA. ILC2s and eosinophils were detected in lung tissue by flow cytometry. The gene expression levels of IL-33 and ST2 were detected by RT-qPCR. RESULTS: Administration of TA reduced pulmonary inflammatory symptoms, MUC5AC production in the BALF, and AHR. At the same time, TA inhibited eotaxin production and eosinophil recruitment. Moreover, TA significantly decreased Th2 and Th17 cytokines and increased Th1 cytokines, contributing to restore the balance between Th1 and Th2 and Th17 cytokines. TA may reduce ILC2s numbers by inhibiting IL-33, IL-25, and TSLP levels in BALF and IL-33/ST2 signaling in lung tissue. Finally, TA decreased tIgE, OVA-IgE, and MCP-1 levels and subsequently inhibited mast cell activation and leukotriene release. CONCLUSIONS: These findings imply that TA may be an effective immunoregulatory medication for the management and prevention of asthma. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Tong, Xiaoyun AU - Tong X AD - School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China; The First Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, 650021, China. FAU - Zhao, Yunli AU - Zhao Y AD - Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, Yunnan Characteristic Plant Extraction Laboratory, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, China. FAU - Fu, Rongbing AU - Fu R AD - School of Pharmacy, Youjiang Medical University for Nationalities, Baise, 533000, China. FAU - Hu, Min AU - Hu M AD - School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China. FAU - Zhang, Qiushi AU - Zhang Q AD - School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China. FAU - Wu, Xiangnong AU - Wu X AD - The First Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, 650021, China. FAU - Qu, Lu AU - Qu L AD - School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China. FAU - Li, Baojing AU - Li B AD - School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China. FAU - Nie, Jian AU - Nie J AD - School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China. FAU - Hu, Chunyan AU - Hu C AD - School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China. FAU - Yu, Xiaoling AU - Yu X AD - The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, 650021, China. FAU - Xie, Yuhuan AU - Xie Y AD - School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China. FAU - Luo, Xiaodong AU - Luo X AD - Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, Yunnan Characteristic Plant Extraction Laboratory, School of Chemical Science and Technology, Yunnan University, Kunming, 650500, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. Electronic address: xdluo@mail.kib.ac.cn. FAU - Huang, Feng AU - Huang F AD - School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming, 650500, China. Electronic address: 14030@ynutcm.edu.cn. LA - eng PT - Journal Article DEP - 20230717 PL - Ireland TA - J Ethnopharmacol JT - Journal of ethnopharmacology JID - 7903310 RN - 9006-59-1 (Ovalbumin) RN - 0 (Interleukin-33) RN - 0 (Interleukin-1 Receptor-Like 1 Protein) RN - 0 (Cytokines) RN - 0 (Alkaloids) RN - 37341-29-0 (Immunoglobulin E) RN - 0 (Leukotrienes) SB - IM MH - Mice MH - Animals MH - *Alstonia MH - Ovalbumin/pharmacology MH - Interleukin-33/metabolism MH - Interleukin-1 Receptor-Like 1 Protein/metabolism MH - Immunity, Innate MH - *Asthma/chemically induced/drug therapy/genetics MH - Lung MH - Cytokines/metabolism MH - *Alkaloids/pharmacology/therapeutic use/metabolism MH - Bronchoalveolar Lavage Fluid MH - Immunoglobulin E MH - Th17 Cells MH - Leukotrienes/metabolism/pharmacology/therapeutic use MH - Mice, Inbred BALB C MH - Disease Models, Animal OTO - NOTNLM OT - Airway inflammation OT - Alstonia scholaris (L.) R. Br. OT - Asthma OT - Th2 cytokines OT - Total alkaloids 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- 2023/07/18 01:09 MHDA- 2023/09/18 12:44 CRDT- 2023/07/17 19:22 PHST- 2023/04/24 00:00 [received] PHST- 2023/07/05 00:00 [revised] PHST- 2023/07/07 00:00 [accepted] PHST- 2023/09/18 12:44 [medline] PHST- 2023/07/18 01:09 [pubmed] PHST- 2023/07/17 19:22 [entrez] AID - S0378-8741(23)00755-9 [pii] AID - 10.1016/j.jep.2023.116887 [doi] PST - ppublish SO - J Ethnopharmacol. 2024 Jan 10;318(Pt A):116887. doi: 10.1016/j.jep.2023.116887. Epub 2023 Jul 17.