Tetrandrine Ameliorates Airway Remodeling of Chronic Asthma by Interfering TGF-β1/Nrf-2/HO-1 Signaling Pathway-Mediated Oxidative Stress

Author:

Lin Yiping1ORCID,Yao Jingchan1ORCID,Wu Meiling2ORCID,Ying Xiaoqian2ORCID,Ding Mingxing3ORCID,Wei Yanli2ORCID,Fu Xiaoyan3,Feng Wei4ORCID,Wang Yunguang5ORCID

Affiliation:

1. Department of Pediatrics, School of Medicine, Jinhua Polytechnic, Jinhua 321007, Zhejiang, China

2. Department of Pharmacology, School of Medicine, Jinhua Polytechnic, Jinhua 321007, Zhejiang, China

3. Department of Histologic, School of Medicine, Jinhua Polytechnic, Jinhua 321007, Zhejiang, China

4. Department of Radiation Oncology, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Cancer Hospital, University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang, China

5. Institute of Nuclear-Agricultural Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China

Abstract

Background. Imbalanced oxidative stress and antioxidant defense are involved in airway remodeling in asthma. It has been demonstrated that Tetrandrine has a potent role in antioxidant defense in rheumatoid arthritis and hypertension. However, the correlation between Tetrandrine and oxidative stress in asthma is utterly blurry. This study aimed to investigate the role of Tetrandrine on oxidative stress-mediated airway remolding. Materials and Methods. Chronic asthma was established by ovalbumin (OVA) administration in male Wistar rats. Histopathology was determined by HE staining. Immunofluorescence was employed to detect the expression of α-SMA and Nrf-2. Level of oxidative stress and matrix metalloproteinases were examined by ELISA kits. Cell viability and cell cycle of primary airway smooth muscle cells (ASMCs) were evaluated by CCK8 and flow cytometry, respectively. Signal molecules were detected using western blot. Results. Tetrandrine effectively impairs OVA-induced airway inflammatory and airway remodeling by inhibiting the expression of CysLT1 and CysLTR1. The increase of oxidative stress and subsequent enhancement of MMP9 and TGF-β1 expression were rescued by the administration of Tetrandrine in the rat model of asthma. In in vitro experiments, Tetrandrine markedly suppressed TGF-β1-evoked cell viability and cell cycle promotion of ASMCs in a dose-dependent manner. Furthermore, Tetrandrine promoted Nrf-2 nuclear transcription and activated its downstream HO-1 in vivo and in vitro. Conclusion. Tetrandrine attenuates airway inflammatory and airway remodeling in rat model of asthma and TGF-β1-induced cell proliferation of ASMCs by regulating oxidative stress in primary ASMCs, suggesting that Tetrandrine possibly is an effective candidate therapy for asthma.

Funder

Jinhua Science and Technology Bureau

Publisher

Hindawi Limited

Subject

Pulmonary and Respiratory Medicine

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