Timosaponin A-III Alleviates Asthma-Induced Airway Inflammation, Th17 Cell Differentiation, and STAT3/RORγt Pathway.

Abstract

Introduction: T helper 17 (Th17) cells have a significant effect in the pathogenesis of asthma, and signal transducer and activator of transcription 3 (STAT3) pathway activation is critical for Th17 cell differentiation. Timosaponin A-III (TA3) was reported to inhibit the STAT3 pathway. Here, we investigated whether TA3 improved asthma by inhibiting the STAT3 pathway.

Methods:  Ovalbumin (OVA)-induced asthma murine models were developed, and TA3 (10 or 20 mg/kg) was gavage daily during OVA challenge. Murine naïve CD4⁺T cells were   triggered for Th17 differentiation, and TA3 (5 or 10 μM) was used to treat cells during induction of Th17 differentiation.

Results: In vivo experiments showed that TA3 decreased airway inflammation, goblet cell and smooth muscle hyperplasia, α-smooth muscle actin and collagen deposition, Th17 differentiation, and STAT3/RORγt signaling activation in mice exposed to OVA. The inhibitory effect of TA3 on STAT3/RORγt signaling activation was also observed in in vitro experiments. Compared to positive control static (a specific inhibitor of STAT3), TA3 had a similar effect on Th17 differentiation.

Discussion: These findings indicate that TA3 may ameliorate Th17 cell differentiation by suppressing STAT3/RORγt signaling. Our data provide evidence of the potential benefits of TA3 for the treatment of asthma.