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Published in: BMC Complementary Medicine and Therapies 1/2021

Open Access 01-12-2021 | Bronchial Asthma | Research article

Suppression of autophagy through JAK2/STAT3 contributes to the therapeutic action of rhynchophylline on asthma

Authors: Hui Li, Qianyu Bi, Hongxia Cui, Chuanfeng Lv, Meng Wang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

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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.
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Literature
1.
go back to reference Rogliani P, Calzetta L, Matera MG, Laitano R, Ritondo BL, Hanania NA, et al. Severe asthma and biological therapy: when, which, and for whom. Pulm Ther. 2020;6(1):47–66.PubMedCrossRef Rogliani P, Calzetta L, Matera MG, Laitano R, Ritondo BL, Hanania NA, et al. Severe asthma and biological therapy: when, which, and for whom. Pulm Ther. 2020;6(1):47–66.PubMedCrossRef
2.
go back to reference Zeki AA, Yeganeh B, Kenyon NJ, Post M, Ghavami S. Autophagy in airway diseases: a new frontier in human asthma? Allergy. 2016;71(1):5–14.PubMedCrossRef Zeki AA, Yeganeh B, Kenyon NJ, Post M, Ghavami S. Autophagy in airway diseases: a new frontier in human asthma? Allergy. 2016;71(1):5–14.PubMedCrossRef
3.
go back to reference Poon AH, Chouiali F, Tse SM, Litonjua AA, Hussain SN, Baglole CJ, et al. Genetic and histologic evidence for autophagy in asthma pathogenesis. J Allergy Clin Immunol. 2012;129(2):569–71.PubMedCrossRef Poon AH, Chouiali F, Tse SM, Litonjua AA, Hussain SN, Baglole CJ, et al. Genetic and histologic evidence for autophagy in asthma pathogenesis. J Allergy Clin Immunol. 2012;129(2):569–71.PubMedCrossRef
4.
go back to reference Zou H, Wang LX, Wang M, Cheng C, Li S, Shen Q, et al. MTOR-mediated autophagy is involved in the protective effect of ketamine on allergic airway inflammation. J Immunol Res. 2019;2019:5879714.PubMedPubMedCentralCrossRef Zou H, Wang LX, Wang M, Cheng C, Li S, Shen Q, et al. MTOR-mediated autophagy is involved in the protective effect of ketamine on allergic airway inflammation. J Immunol Res. 2019;2019:5879714.PubMedPubMedCentralCrossRef
5.
go back to reference Gu W, Cui R, Ding T, Li X, Peng J, Xu W, et al. Simvastatin alleviates airway inflammation and remodelling through up-regulation of autophagy in mouse models of asthma. Respirology. 2017;22(3):533–41.PubMedCrossRef Gu W, Cui R, Ding T, Li X, Peng J, Xu W, et al. Simvastatin alleviates airway inflammation and remodelling through up-regulation of autophagy in mouse models of asthma. Respirology. 2017;22(3):533–41.PubMedCrossRef
6.
go back to reference Song Y, Qu R, Zhu S, Zhang R, Ma S. Rhynchophylline attenuates LPS-induced pro-inflammatory responses through down-regulation of MAPK/NF-kappaB signaling pathways in primary microglia. Phytother Res. 2012;26(10):1528–33.PubMed Song Y, Qu R, Zhu S, Zhang R, Ma S. Rhynchophylline attenuates LPS-induced pro-inflammatory responses through down-regulation of MAPK/NF-kappaB signaling pathways in primary microglia. Phytother Res. 2012;26(10):1528–33.PubMed
7.
go back to reference Qin QJ, Cui LQ, Li P, Wang YB, Zhang XZ, Guo ML. Rhynchophylline ameliorates myocardial ischemia/reperfusion injury through the modulation of mitochondrial mechanisms to mediate myocardial apoptosis. Mol Med Rep. 2019;19(4):2581–90.PubMedPubMedCentral Qin QJ, Cui LQ, Li P, Wang YB, Zhang XZ, Guo ML. Rhynchophylline ameliorates myocardial ischemia/reperfusion injury through the modulation of mitochondrial mechanisms to mediate myocardial apoptosis. Mol Med Rep. 2019;19(4):2581–90.PubMedPubMedCentral
8.
go back to reference Wang M, Li H, Zhao Y, Lv C, Zhou G. Rhynchophylline attenuates allergic bronchial asthma by inhibiting transforming growth factor-beta1-mediated Smad and mitogen-activated protein kinase signaling transductions in vivo and in vitro. Exp Ther Med. 2019;17(1):251–9.PubMed Wang M, Li H, Zhao Y, Lv C, Zhou G. Rhynchophylline attenuates allergic bronchial asthma by inhibiting transforming growth factor-beta1-mediated Smad and mitogen-activated protein kinase signaling transductions in vivo and in vitro. Exp Ther Med. 2019;17(1):251–9.PubMed
9.
go back to reference Lv J, Sun B, Mai Z, Jiang M, Du J. STAT3 potentiates the ability of airway smooth muscle cells to promote angiogenesis by regulating VEGF signalling. Exp Physiol. 2017;102(5):598–606.PubMedCrossRef Lv J, Sun B, Mai Z, Jiang M, Du J. STAT3 potentiates the ability of airway smooth muscle cells to promote angiogenesis by regulating VEGF signalling. Exp Physiol. 2017;102(5):598–606.PubMedCrossRef
10.
go back to reference Yang Q, Xu W, Long Y, Kuang J, Li J. STAT3 regulates cytokine expression in peripheral blood mononuclear cells from asthma patients. Cell Mol Biol (Noisy-le-Grand). 2017;63(9):71–4.CrossRef Yang Q, Xu W, Long Y, Kuang J, Li J. STAT3 regulates cytokine expression in peripheral blood mononuclear cells from asthma patients. Cell Mol Biol (Noisy-le-Grand). 2017;63(9):71–4.CrossRef
11.
go back to reference Gavino AC, Nahmod K, Bharadwaj U, Makedonas G, Tweardy DJ. STAT3 inhibition prevents lung inflammation, remodeling, and accumulation of Th2 and Th17 cells in a murine asthma model. Allergy. 2016;71(12):1684–92.PubMedCrossRef Gavino AC, Nahmod K, Bharadwaj U, Makedonas G, Tweardy DJ. STAT3 inhibition prevents lung inflammation, remodeling, and accumulation of Th2 and Th17 cells in a murine asthma model. Allergy. 2016;71(12):1684–92.PubMedCrossRef
12.
go back to reference Dascani P, Ding C, Kong X, Tieri D, Hu X, Zhang HG, et al. Transcription factor STAT3 serves as a negative regulator controlling IgE class switching in mice. Immunohorizons. 2018;2(11):349–62.PubMedCrossRef Dascani P, Ding C, Kong X, Tieri D, Hu X, Zhang HG, et al. Transcription factor STAT3 serves as a negative regulator controlling IgE class switching in mice. Immunohorizons. 2018;2(11):349–62.PubMedCrossRef
13.
go back to reference Koltsida O, Karamnov S, Pyrillou K, Vickery T, Chairakaki AD, Tamvakopoulos C, et al. Toll-like receptor 7 stimulates production of specialized pro-resolving lipid mediators and promotes resolution of airway inflammation. EMBO Mol Med. 2013;5(5):762–75.PubMedPubMedCentralCrossRef Koltsida O, Karamnov S, Pyrillou K, Vickery T, Chairakaki AD, Tamvakopoulos C, et al. Toll-like receptor 7 stimulates production of specialized pro-resolving lipid mediators and promotes resolution of airway inflammation. EMBO Mol Med. 2013;5(5):762–75.PubMedPubMedCentralCrossRef
14.
go back to reference Koltsida O, Hausding M, Stavropoulos A, Koch S, Tzelepis G, Ubel C, et al. IL-28A (IFN-lambda2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease. EMBO Mol Med. 2011;3(6):348–61.PubMedPubMedCentralCrossRef Koltsida O, Hausding M, Stavropoulos A, Koch S, Tzelepis G, Ubel C, et al. IL-28A (IFN-lambda2) modulates lung DC function to promote Th1 immune skewing and suppress allergic airway disease. EMBO Mol Med. 2011;3(6):348–61.PubMedPubMedCentralCrossRef
15.
go back to reference Long H, Ruan J, Zhang M, Wang C, Huang Y. Rhynchophylline attenuates Tourette syndrome via BDNF/NF-kappaB pathway in vivo and in vitro. Neurotox Res. 2019;36(4):756–63.PubMedCrossRef Long H, Ruan J, Zhang M, Wang C, Huang Y. Rhynchophylline attenuates Tourette syndrome via BDNF/NF-kappaB pathway in vivo and in vitro. Neurotox Res. 2019;36(4):756–63.PubMedCrossRef
16.
go back to reference Zhang Y, Sun J, Zhu S, Xu T, Lu J, Han H, et al. The role of rhynchophylline in alleviating early brain injury following subarachnoid hemorrhage in rats. Brain Res. 2016;1631:92–100.PubMedCrossRef Zhang Y, Sun J, Zhu S, Xu T, Lu J, Han H, et al. The role of rhynchophylline in alleviating early brain injury following subarachnoid hemorrhage in rats. Brain Res. 2016;1631:92–100.PubMedCrossRef
17.
go back to reference Wang ZJ, Chang LL, Wu J, Pan HM, Zhang QY, Wang MJ, et al. A novel Rhynchophylline analog, Y396, inhibits endothelial dysfunction induced by oxidative stress in diabetes through epidermal growth factor receptor. Antioxid Redox Signal. 2020;32(11):743–65.PubMedCrossRef Wang ZJ, Chang LL, Wu J, Pan HM, Zhang QY, Wang MJ, et al. A novel Rhynchophylline analog, Y396, inhibits endothelial dysfunction induced by oxidative stress in diabetes through epidermal growth factor receptor. Antioxid Redox Signal. 2020;32(11):743–65.PubMedCrossRef
18.
go back to reference Sachdeva K, Do DC, Zhang Y, Hu X, Chen J, Gao P. Environmental exposures and asthma development: autophagy, Mitophagy, and cellular senescence. Front Immunol. 2019;10:2787.PubMedPubMedCentralCrossRef Sachdeva K, Do DC, Zhang Y, Hu X, Chen J, Gao P. Environmental exposures and asthma development: autophagy, Mitophagy, and cellular senescence. Front Immunol. 2019;10:2787.PubMedPubMedCentralCrossRef
19.
go back to reference Zhang Y, Tang H, Yuan X, Ran Q, Wang X, Song Q, et al. TGF-beta3 promotes MUC5AC hyper-expression by modulating autophagy pathway in airway epithelium. EBioMedicine. 2018;33:242–52.PubMedPubMedCentralCrossRef Zhang Y, Tang H, Yuan X, Ran Q, Wang X, Song Q, et al. TGF-beta3 promotes MUC5AC hyper-expression by modulating autophagy pathway in airway epithelium. EBioMedicine. 2018;33:242–52.PubMedPubMedCentralCrossRef
20.
go back to reference Lin L, Zhang L, Li XT, Ji JK, Chen XQ, Li YL, et al. Rhynchophylline attenuates senescence of endothelial progenitor cells by enhancing autophagy. Front Pharmacol. 2019;10:1617.PubMedCrossRef Lin L, Zhang L, Li XT, Ji JK, Chen XQ, Li YL, et al. Rhynchophylline attenuates senescence of endothelial progenitor cells by enhancing autophagy. Front Pharmacol. 2019;10:1617.PubMedCrossRef
21.
go back to reference Hongyan L, Mengjiao Z, Chunyan W, Yaruo H. Rhynchophyllin attenuates neuroinflammation in Tourette syndrome rats via JAK2/STAT3 and NF-kappaB pathways. Environ Toxicol. 2019;34(10):1114–20.PubMedCrossRef Hongyan L, Mengjiao Z, Chunyan W, Yaruo H. Rhynchophyllin attenuates neuroinflammation in Tourette syndrome rats via JAK2/STAT3 and NF-kappaB pathways. Environ Toxicol. 2019;34(10):1114–20.PubMedCrossRef
Metadata
Title
Suppression of autophagy through JAK2/STAT3 contributes to the therapeutic action of rhynchophylline on asthma
Authors
Hui Li
Qianyu Bi
Hongxia Cui
Chuanfeng Lv
Meng Wang
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-020-03187-w

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