Banhahubak-tang tablet, a standardized medicine attenuates allergic asthma via inhibition of Janus kinase 1 (JAK1)/ signal transducer and activator of transcription 6 (STAT6) signal pathway

Abstract

Exposure to particulate matter (PM) has been known to be one of the risk factors to cause allergic asthma, leading to development of respiratory disease. Banhahubak-tang tablet (BHT), a standardized Korean Medicine, is prescribed for neurasthenia, laryngopharyngitis and asthma. In this study, we investigated therapeutic effects of BHT on airway inflammation in ovalbumin (OVA) and PM smaller than 10 μm (PM10)-induced allergic asthma mice. To establish allergic asthma with airway hyper-responsiveness by PM10, BALB/c mice were sensitized and challenged with OVA and PM10, and orally administered BHT. Histological staining was performed to assess airway remodeling. Serum and bronchoalveolar lavage fluid (BALF) was collected for measuring immunoglobulin levels and counting inflammatory cells, respectively. Expression levels of Janus kinase 1 (JAK1)/signal transducer and activator of transcription 6 (STAT6), pro-inflammatory cytokines and type 2 T-helper (Th2)-related cytokines were analyzed in vivo and in vitro models. Histopathological analysis demonstrated that BHT suppressed inflammatory cell infiltration, mucus hypersecretion and collagen deposition in the airway. BHT administration effectively decreased number of inflammatory cells in BALF. BHT reduced total serum Immunoglobulin E (IgE) and Immunoglobulin G (IgG) levels. In addition, BHT significantly inhibited the phosphorylation of JAK1 and STAT6 expressions. Release of pro-inflammatory cytokines and Th2-related cytokines were down-regulated by BHT. In conclusion, BHT mitigated airway inflammation by down-regulating pro-inflammatory and Th2-related cytokines via JAK1/STAT6 signaling. BHT might be a promising herbal medicine for preventing airway inflammation. Moreover, an intervention study among humans is needed to further evaluate the possible beneficial effects of BHT in allergic asthma.