Effects of Shiwei Longdanhua formula on LPS induced airway mucus hypersecretion, cough hypersensitivity, oxidative stress and pulmonary inflammation.

ABSTRACT

Shiwei Longdanhua Granule (SWLDH) is a classic Tibetan medicine (TM) ranking in the top 20 Chinese patent medicines in prescription rate to treat respiratory diseases like pneumonia, acute and chronic tracheobronchitis, acute exacerbation of COPD and bronchial asthma in solution of inflammation, cough and phlegm obstruction in clinical practice. However, its systematic pharmacological mechanisms have not been elucidated yet. Here, we studied the therapeutic efficacy of SWLDH in treatment of acute respiratory diseases in BALB/c mice by comprehensive analysis of airway inflammation, oxidative stress, mucus hypersecretion, cough hypersensitivities and indicators associated with the development of chronic diseases. Our results show that SWLDH might exhibit its inhibitory effects on pulmonary inflammation by interference with arachidonic acid (AA) metabolism pathways. Oxidative stress that highly related to the degree of tissue injury could be alleviated by enhancing the reductive activities of glutathione redox system, thioredoxin system and the catalytic activities of catalase and superoxide dismutase (SOD) after SWLDH treatment. In addition, SWLDH could significantly abrogate the mucus hypersecretion induced bronchiole obstruction by inactivate the globlet cells and decrease the secretion of gel-forming mucins (MUC5AC and MUC5B) under pathological condition, demonstrating its mucoactive potency. SWLDH also showed reversed effects on the release of neuropeptides that are responsible for airway sensory hypersensitivity. Simultaneously observed inhibition of calcium influx, reduction in in vivo biosynthesis of acetylcholine and the recovery of the content of cyclic adenosine monophosphate (cAMP) might collaboratively contribute to cause airway smooth muscle cells (ASMCs) relexation. These findings indicated that SWLDH might exhibited antitussive potency via suppression of the urge to cough and ASMCs contraction. Moreover, SWLDH might affect airway remodeling. We found SWLDH could retard the elevation of TGF-ß1 and α-SMA, which are important indicators for hyperplasia and contraction during the progression of the chronic airway inflammatory diseases like COPD and asthma.