Esculentoside a attenuates airway inflammation in asthma by regulating mitochondrial apoptosis via the JAK2/STAT3...

This study aimed to investigate whether esculentoside A (EsA) alleviates airway inflammation by modulating JAK2/STAT3-mediated mitochondrial apoptosis in an ovalbumin (OVA)-induced murine model of asthma.

Female BALB/c mice were sensitized and challenged with OVA to establish the asthma model. EsA (15 mg/kg) was administered intraperitoneally from day 17 for seven consecutive days. JAK2 inhibitor (Fedratinib, 60 mg/kg) and JAK2 agonist (C-A1, 100 μg/kg) were used to further validate the involvement of the JAK2/STAT3 pathway. Histological analysis, ELISA, Western blot, TUNEL, and mitochondrial function assays were performed to evaluate inflammatory response, apoptosis, and signaling pathways.

EsA treatment significantly alleviated airway inflammation, as shown by reduced peribronchial inflammatory infiltration and lower inflammation scores, and decreased goblet cell hyperplasia and PAS staining scores. ELISA results showed that EsA significantly reduced IL-4, IL-13, and TNF-β levels in BALF and decreased serum OVA-specific IgE. Western blot revealed that EsA downregulated phosphorylated JAK2 and STAT3 levels, as well as proapoptotic markers (Bax, Cyt C, and cleaved Caspase-3), while upregulating the antiapoptotic protein Bcl-2. These effects were comparable to those of Fedratinib and were reversed by JAK2 agonist C-A1. Furthermore, EsA restored mitochondrial membrane potential (JC-1 ratio increased) and reduced mitochondrial ROS production, indicating improved mitochondrial function. TUNEL assays corroborated the antiapoptotic effect of EsA.

: EsA ameliorates OVA-induced airway inflammation in mice, likely by suppressing the JAK2/STAT3 signaling pathway and attenuating mitochondrial-dependent apoptosis. These findings suggest that EsA holds therapeutic potential as a novel anti-asthmatic agent targeting inflammatory and mitochondrial pathways.