Chinese herbal formula Regan Saibisitan alleviates airway inflammation of chronic bronchitis via inhibiting the JAK2/STAT3 pathway

Ethnopharmacological relevance: Regan Saibisitan (RGS) is a classic prescription used to treat cough, pneumonia, and other respiratory infections in Uygur medicine. It is a granule composed of 12 kinds of medicinal materials. However, the mechanism by which RGS regulates lung disease remains unclear.

Aim of the study: Chronic bronchitis (CB) is characterized by persistent, non-specific inflammation in the trachea, bronchial mucosa, and surrounding tissues mainly resulting from infectious or non-infectious factors. This study aimed to explore the function of RGS in alleviating airway inflammation associated with chronic bronchitis, and to examine the mechanisms by which RGS exerts its effects via the JAK 2/STAT 3 signaling pathway.

Materials and methods: The CB mouse model was established by cigarette smoking (CS) and intranasal administration of lipopolysaccharide (LPS, 20 μg), histological changes of bronchial epithelium, collagen deposition, mucus secretion in lung tissue and inflammatory factors were assayed. Transcriptomics analysis was performed to detect the differentially regulated genes in lung tissue of CB mice treated with RGS. The effect of RGS on JAK 2/STAT 3 pathway was investigated in CB mice and NCI-H292 cells treated with PMA using western blotting, ELISA, and immunohistochemical analysis.

Results: RGS treatment significantly improved the thickening of bronchial epithelium, decreased collagen deposition and secretion of mucus, and the levels of inflammatory factors in CB mice. Transcriptomics analysis showed that most of 402 differentially expressed genes in RGS-treated CB mice were related to inflammatory response. The results in CB mice and NCI-H292 cells showed that RGS reduced the phosphorylation level of JAK 2 and STAT 3. In addition, the use of JAK 2 inhibitor AG490 confirmed that JAK 2/STAT 3 pathway played a key role in the effects of RGS on CB.

Conclusions: RGS suppresses inflammation and improves chronic bronchitis in NCI-H292 cells and CB mice, at least in part, via inhibiting the JAK 2/STAT 3 pathway. This study demonstrated that RGS could be a potential drug in treating CB disease.