Author/Authors :
Lin, Yiping Department of Pediatrics - School of Medicine - Jinhua Polytechnic, Jinhua, Zhejiang, China , Yao, Jingchan Department of Pediatrics - School of Medicine - Jinhua Polytechnic, Jinhua, Zhejiang, China , Wu, Meiling Department of Pharmacology - School of Medicine - Jinhua Polytechnic, Jinhua, Zhejiang, China , Ying, Xiaoqian Department of Pharmacology - School of Medicine - Jinhua Polytechnic, Jinhua, Zhejiang, China , Ding, Mingxing Department of Histologic - School of Medicine - Jinhua Polytechnic, Jinhua, Zhejiang, China , Wei, Yanli Department of Pharmacology - School of Medicine - Jinhua Polytechnic, Jinhua, Zhejiang, China , Fu, Xiaoyan Department of Histologic - School of Medicine - Jinhua Polytechnic, Jinhua, Zhejiang, China , Feng, Wei 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, Zhejiang, China , Wang, Yunguang Institute of Nuclear-Agricultural Sciences - Zhejiang University, Hangzhou, 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.
