Abstract
This study aimed to investigate the effects of the coadministration of budesonide (Bud) and the extracts of Epimedii Folium and Ligustri Lucidi Fructus (EEL) on regulating apoptosis and autophagy in asthmatic rats. Forty Sprague-Dawley rats were divided randomly into five groups (8 rats in each group): normal control (control), asthma model (asthma), Bud (1 mg Bud suspension in 50 ml sterile physiological saline for 30 min), EEL (100 mg/kg EEL), and group of coadministration of Bud and EEL (Bud&EEL, 100 mg/kg EEL plus Bud by nebulized inhalation for 30 min). Rats were sensitized and challenged with ovalbumin for 7 weeks and treated with corresponding drug for 4 weeks. We anesthetized all rats with 25% ethyl carbamate (4 ml/kg) and took lung tissues and BALF after final ovalbumin challenge to observe the lung histopathology and morphometry; apoptosis in BALF and lung tissue; protein expressions of Ki-67, α-SMA, cleaved Caspase-3, p-mTOR, and LC3; and protein and mRNA expressions of Bax, Bcl-2, Caspase-3, P53, mTOR, and Beclin-1. Results showed that Bud&EEL could alleviate airway remodeling, inhibit cell proliferation and autophagy in lung tissue, and promote apoptosis in BALF and lung tissue in ovalbumin-induced asthma rats through downregulating the protein expressions of α-SMA and Ki-67, the protein ratio of LC3-II/LC3-I and Bcl-2/Bax, and the protein and mRNA expressions of Bcl-2 and Beclin-1, while upregulating the protein expressions of cleaved Caspase-3 and p-mTOR, and the protein and mRNA expressions of Bax, Caspase-3, P53, and mTOR. Bud&EEL had better effects than single-use Bud on improving airway remodeling, promoting apoptosis, and regulating the expressions of autophagy- and apoptosis-related proteins. This study suggested that the effects of coadministration of EEL and Bud on regulating apoptosis and autophagy were better than those of single-use Bud treatment, and that might be the mechanism of attenuating airway remodeling, providing an alternative therapy for asthma.
Highlights
Asthma is one of the most serious chronic respiratory diseases characterized by airway inflammation, airway remodeling, and bronchial hyperresponsiveness
We found that the coadministration of extracts of Epimedii Folium (EF) and Ligustri Lucidi Fructus (LLF) (EEL) and GCs had better effects on airway remodeling and inflammation by reducing the levels of interleukin-4 (IL-4), IL-5, and IgE in serum and inhibiting the TGF-β1/Smad pathway in ovalbumin-induced asthmatic rats compared with single-use GC treatment [37, 38]; EEL can increase the sensitivity of asthmatic rats to budesonide by promoting lymphocyte apoptosis and balancing GR/HSP90 [39]
Severe inflammation, mucosal edema, epithelial lesions, and inflammatory cell infiltration including lymphocyte and eosinophil were observed in asthma model group which were attenuated by administration of Bud, EEL, or Bud and EEL (Bud&EEL)
Summary
Asthma is one of the most serious chronic respiratory diseases characterized by airway inflammation, airway remodeling, and bronchial hyperresponsiveness. It affects all age brackets [1, 2], and its morbidity and mortality are increasing year by year worldwide [3]. Airway remodeling—regarded as a primary cause of refractory asthma—is characterized by epithelial shedding, goblet cell hyperplasia, basal membrane thickening, airway smooth muscle cell hyperplasia and hypertrophy, and bronchial vasculature angiogenesis [4]. It occurs in all-age asthmatic patients and can exacerbate airway inflammation and bronchial hyperresponsiveness [5]. Improving therapeutic and side effects of GCs through drug combination has a great significance for the treatment of asthma
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