Data Sheet 1_Notoginsenoside R1 modulates the ATF4-CHOP-Bcl2 signaling pathway to alleviate mitochondrial stress damage and apoptosis in asthmatic airway epithelial cells.pdf

Objective<p>To investigate whether Notoginsenoside R1 (NG-R1) improves mitochondrial homeostasis by targeting the integrin signaling response (ISR) core transcription factor ATF4, thereby alleviating damage and apoptosis in asthma airway epithelial cells.</p>Methods<p>House dust mites (HDM) were used to establish an in vivo asthma mouse model and an in vitro BEAS-2B cell model. The anti-inflammatory and immunomodulatory effects of NG-R1 were evaluated through pulmonary function testing, bronchoalveolar lavage fluid (BALF) cell counting, and hematoxylin and eosin (H&E) staining.

We evaluated the effects of NG-R1 on apoptosis and mitochondrial function using TUNEL, Annexin V-FITC/PI staining, transmission electron microscopy, MitoSox Red, TMRE, JC-1, and Western blot analysis of mitochondrial dynamics-related proteins (p-Drp1/Drp1, Mfn2, ATP5F1A). We used lentiviral knockdown of ATF4 combined with RNA-seq, GO enrichment analysis, and the STRING database to predict its downstream mechanisms. Molecular docking was used to predict the binding affinity between NG-R1 and ATF4, and the expression levels of ATF4, CHOP, and Bcl-2 were validated using Western blot analysis in both in vivo and in vitro models.</p>Results<p>ATF4 expression was significantly elevated in lung tissue from asthmatic mice and in HDM-stimulated BEAS-2B cells, and was positively correlated with increased epithelial cell apoptosis and reduced migration and repair capacity.