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

Liu Wei; Hou Hongping; Li Chufang; Mingji Cuomu; Li Jintao; Cai Kaiyin; Chen Lvyi; Chen Weiwu; Ye Zuguang; Zhong Nanshan

doi:10.1016/j.biopha.2023.114793

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

Biomed Pharmacother. 2023 Jul:163:114793. doi: 10.1016/j.biopha.2023.114793. Epub 2023 Apr 28.

Authors

Liu Wei¹, Hou Hongping², Li Chufang³, Mingji Cuomu⁴, Li Jintao⁵, Cai Kaiyin⁶, Chen Lvyi⁷, Chen Weiwu⁸, Ye Zuguang⁹, Zhong Nanshan¹⁰

Affiliations

¹ Guangzhou Laboratory, Guangzhou, China; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
² Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
³ Guangzhou Laboratory, Guangzhou, China.
⁴ The University of Tibetan Medicine, Lhasa, China.
⁵ Beijing International Science and Technology Cooperation Base of Antivirus Drug, Beijing University of Technology, Beijing, China.
⁶ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China; Tibet Cheezheng Tibet Medicine Co.,Ltd., Beijing, China.
⁷ School of Pharmaceutical Sciences, South-Central Minzu University, Wuhan, China.
⁸ Tibet Cheezheng Tibet Medicine Co.,Ltd., Beijing, China.
⁹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China. Electronic address: zgye@icmm.ac.cn.
¹⁰ Guangzhou Laboratory, Guangzhou, China; State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China. Electronic address: nanshan@vip.163.com.

PMID: 37121151
DOI: 10.1016/j.biopha.2023.114793

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-β1 and α-SMA, which are important indicators for hyperplasia and contraction during the progression of the chronic airway inflammatory diseases like COPD and asthma.

Keywords: Airway contraction; Mucin hypersecretion; Neurogenic inflammation; Oxidative stress; Pulmonary inflammation.

MeSH terms

Animals
Asthma* / drug therapy
Chronic Disease
Cough / chemically induced
Cough / drug therapy
Hypersensitivity*
Inflammation / drug therapy
Inflammation / metabolism
Lipopolysaccharides / metabolism
Mice
Mucin 5AC / metabolism
Mucus / metabolism
Oxidative Stress
Pneumonia* / chemically induced
Pneumonia* / drug therapy
Pneumonia* / metabolism
Pulmonary Disease, Chronic Obstructive* / drug therapy
Pulmonary Disease, Chronic Obstructive* / metabolism

Substances

shiwei
Lipopolysaccharides
Mucin 5AC