Background: 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. Regan Saibisitan is a classic prescription used to treat cough, pneumonia, and other respiratory infections in Uygur medicine. However, its mechanism in treating chronic bronchitis has not been reported. This study aimed to explore the efficacy and mechanism of Regan Saibisitan in CB mice.
Methods: Regan Saibisitan extract (RGS) was prepared, and the components in RGS were analyzed by ultra-performance liquid chromatography-ion trap-electrostatic field orbital trap mass spectrometry (UPLC-LTQ-Orbitrap-MS/MS). The CB mouse model was established by cigarette smoking (CS) and intranasal administration of lipopolysaccharide (LPS, 20μg), 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-H 282 cells treated with PMA using western blotting, ELISA,and immunohistochemical analysis. The JAK2 inhibitor AG490 was used in NCI-H292 cells to verify the effect of RGS on JAK2/STAT3 pathway.
Results: A total of 286 compounds were identified in RGS, in which Liquiritin, Formononetin, Isoliquiritigenin, Salidroside, Ferulic and Morphine were reported to have significant anti-inflammatory activities. 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 JAK2 inhibitor AG490 confirmed that JAK2/STAT3 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 JAK2/STAT3 pathway. This study demonstrated that RGS could be a potential drug in treating CB disease.
