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

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.

Combined Extracts of Epimedii Folium and Ligustri Lucidi Fructus with Budesonide Attenuate Airway Remodeling in the Asthmatic Rats by Regulating Apoptosis and Autophagy

“…Airway remodeling is an irreversible change in airway structure and function induced by chronic impairment, relating to severity of asthma [ 57 , 58 ]. At present, asthmatic treatments (including GCs and long-acting β 2-agonist and bronchodilators) have little influence on airway remodeling, the primary cause of refractory asthma [ 59 ]. In our study, Bud&EEL relieved the incrassation of the airway wall and smooth muscle, goblet cell hyperplasia, and collagen deposition in ovalbumin-induced asthma rats.…”

Tetrandrine Citrate Suppresses Breast Cancer via Depletion of Glutathione Peroxidase 4 and Activation of Nuclear Receptor Coactivator 4-Mediated Ferritinophagy

“…A previous study has also indicated that 10 μM Tet does not affect the viability of MPC5 podocytes ( Ding et al, 2021b ). In addition, preincubation with 20 μM Tet slightly reduced the viability of HaCaT human keratinocyte cells ( Lin et al, 2019 ). In the present study, we demonstrated that the IC50 of TetC for MCF7 and MDA-MB-231 cells were 21.76 and 8.76 μmol/l, respectively, indicating that low dose of TetC significantly led to breast cancer cell death.…”

Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways

“…The antioxidative stress response is carried out through Nrf2/HO‐1 pathway. It is shown that HO‐1 reduces inflammation, airway oxidative stress, excessive mucus secretion, and asthma responses 37,38 . Nrf2 is stored in the cytoplasm and binds to Keap 1 in normal state 39 .…”