Hui Li1, Qianyu Bi2, Hongxia Cui3, Chuanfeng Lv4, Meng Wang5,6. 1. Department of Medical Affairs, Jining No. 1 People's Hospital, Jiankang Road, Jining, Shandong, 272011, People's Republic of China. 2. Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People's Republic of China. 3. Department of Oncology, Jining No. 1 People's Hospital, Jining, Shandong, 272011, People's Republic of China. 4. Department of Pharmacology, Jining No. 1 People's Hospital, Jining, Shandong, 272011, People's Republic of China. 5. Department of Medical Affairs, Jining No. 1 People's Hospital, Jiankang Road, Jining, Shandong, 272011, People's Republic of China. wangmeng106@163.com. 6. Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, 250355, People's Republic of China. wangmeng106@163.com.
Abstract
BACKGROUND: Asthma is a chronic inflammatory disease characterized by airway remodeling and inflammation. Rhynchophylline is a kind of indole alkaloid isolated from Uncaria rhynchophylla. Here we investigated the effect of rhynchophylline on autophagy in asthma. METHODS: A mice model of asthma was established by ovalbumin challenge. Histopathological changes were assessed by hematoxylin-eosin staining, periodic acid-schiff staining and Masson staining. The levels of IgE in serum, interleukin-6 and interleukin-13 in bronchoalveolar lavage fluid, as well as the activities of superoxide dismutase and catalase in lung tissues were detected. The expression of autophagy-related genes and Janus kinase (JAK) 2/ signal transducer and activator of transcription (STAT) 3 signal was detected by western blot and immunofluorescence. Airway smooth muscle cells (ASMCs) were isolated, and the effect rhynchophylline on autophagy in ASMCs was explored. RESULTS: Our data showed that rhynchophylline treatment alleviated inflammation, airway remodeling, and oxidative stress in asthma. In addition, autophagy, which was implicated in asthma, was suppressed by rhynchophylline with decreased level of autophagy-related proteins. Furthermore, rhynchophylline suppressed the JAK2/STAT3 signaling pathway, which was activated in asthma. In vitro study showed that rhynchophylline suppressed ASMC autophagy through suppressing the activation of JAK2/STAT3 signal. CONCLUSIONS: Our study demonstrated that rhynchophylline can alleviate asthma through suppressing autophagy in asthma, and that JAK2/STAT3 signal was involved in this effect of rhynchophylline. This study indicates that rhynchophylline may become a promising drug for the treatment of asthma.
BACKGROUND:Asthma is a chronic inflammatory disease characterized by airway remodeling and inflammation. Rhynchophylline is a kind of indole alkaloid isolated from Uncaria rhynchophylla. Here we investigated the effect of rhynchophylline on autophagy in asthma. METHODS: A mice model of asthma was established by ovalbumin challenge. Histopathological changes were assessed by hematoxylin-eosin staining, periodic acid-schiff staining and Masson staining. The levels of IgE in serum, interleukin-6 and interleukin-13 in bronchoalveolar lavage fluid, as well as the activities of superoxide dismutase and catalase in lung tissues were detected. The expression of autophagy-related genes and Janus kinase (JAK) 2/ signal transducer and activator of transcription (STAT) 3 signal was detected by western blot and immunofluorescence. Airway smooth muscle cells (ASMCs) were isolated, and the effect rhynchophylline on autophagy in ASMCs was explored. RESULTS: Our data showed that rhynchophylline treatment alleviated inflammation, airway remodeling, and oxidative stress in asthma. In addition, autophagy, which was implicated in asthma, was suppressed by rhynchophylline with decreased level of autophagy-related proteins. Furthermore, rhynchophylline suppressed the JAK2/STAT3 signaling pathway, which was activated in asthma. In vitro study showed that rhynchophylline suppressed ASMC autophagy through suppressing the activation of JAK2/STAT3 signal. CONCLUSIONS: Our study demonstrated that rhynchophylline can alleviate asthma through suppressing autophagy in asthma, and that JAK2/STAT3 signal was involved in this effect of rhynchophylline. This study indicates that rhynchophylline may become a promising drug for the treatment of asthma.
Authors: Paul Dascani; Chuanlin Ding; Xiangyu Kong; David Tieri; Xiaoling Hu; Huang-Ge Zhang; Daisuke Kitamura; Roberto Bolli; Eric C Rouchka; Jun Yan Journal: Immunohorizons Date: 2018-12-05
Authors: Ourania Koltsida; Michael Hausding; Athanasios Stavropoulos; Sonja Koch; George Tzelepis; Caroline Ubel; Sergei V Kotenko; Paschalis Sideras; Hans A Lehr; Marcus Tepe; Kevin M Klucher; Sean E Doyle; Markus F Neurath; Susetta Finotto; Evangelos Andreakos Journal: EMBO Mol Med Date: 2011-05-03 Impact factor: 12.137