title: Pinellia ternata Attenuates Mucus Secretion and Airway Inflammation after Inhaled Corticosteroid Withdrawal in COPD Rats.
abstract: Inhaled corticosteroids (ICS) are widely used to manage chronic obstructive pulmonary disease (COPD). However, withdrawal of ICS generally causes various adverse effects, warranting careful management of the ICS withdrawal. Pinellia ternata, a traditional Chinese herbal medicine, has been used to treat respiratory diseases in China for centuries. Here, we investigated its role in antagonizing ICS withdrawal-induced side effects, and explored the underlying mechanisms. The rat COPD model was established using a combination of passive cigarette smoking and intratracheal instillation of lipopolysaccharide (LPS). COPD rats were treated with saline or budesonide inhalation, or with budesonide inhalation followed by saline inhalation or Pinellia ternata gavage. The number of goblet cells and the level of mucin 5AC (MUC5AC) were enhanced by budesonide withdrawal. Pinellia ternata treatment significantly blocked these effects. Further, Pinellia ternata treatment reversed budesonide withdrawal-induced increase of interleukin 1[Formula: see text] (IL-1[Formula: see text] and tumor necrosis factor [Formula: see text] (TNF-[Formula: see text]) levels in bronchoalveolar lavage fluid (BALF). Extracellular signal-regulated kinase (ERK), but neither p38 nor c-Jun N-terminal kinase (JNK), was activated by budesonide withdrawal, and the activation was blocked by Pinellia ternata treatment. The MUC5AC expression was positively correlated with goblet cell number, IL-1[Formula: see text] and TNF-[Formula: see text] levels, and ERK activity. Pinellia ternata treatment protected the airway from ICS withdrawal-induced mucus hypersecretion and airway inflammation by inhibiting ERK activation. Pinellia ternata treatment may represent a novel therapeutic strategy to prevent ICS withdrawal-induced side effects in COPD patients.
authors.affiliation: * Department of Pathophysiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|‡ Respiratory Diseases Group, the 6th Unit, Department of Internal Medicine, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.affiliation: * Department of Pathophysiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Su
authors.affiliation: § Hexian Memorial Hospital, Panyu, Guangzhou 511400, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ye
authors.affiliation: † Department of Cardiovascular Diseases, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yuegang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: * Department of Pathophysiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
authors.affiliation: * Department of Pathophysiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.|¶ Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge 14183, Sweden.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Gong
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008297:Male; D055271:Mucin 5AC / Q000235:genetics / Q000276:immunology; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism; D030021:Pinellia / Q000737:chemistry*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000209:etiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D004365:Drugs, Chinese Herbal; D007375:Interleukin-1; D055271:Mucin 5AC; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Budesonide; Chronic Obstructive Pulmonary Disease; Corticosteroids Withdrawal; Extracellular Signal-Regulated Kinase; Mucin 5AC; Pinellia ternata