Cigarette Smoke-Induced Lung Disease Predisposes to More Severe Infection with Nontypeable Haemophilus influenzae: Protective Effects of Andrographolide.
Cigarette smoke (CS) is associated with many maladies, one of which is chronic obstructive pulmonary disease (COPD). As the disease progresses, patients are more prone to develop COPD exacerbation episodes by bacterial infection, particularly to nontypeable Haemophilus influenza (NTHi) infection. The present study aimed to develop a CS-exposed mouse model that increases inflammation induced by NTHi challenge and investigate the protective effects of andrographolide, a bioactive molecule with anti-inflammatory and antioxidant properties isolated from the plant Andrographis paniculata. Female BALB/c mice exposed to 2 weeks of CS followed by a single intratracheal instillation of NTHi developed increased macrophage and neutrophil pulmonary infiltration, augmented cytokine levels, and heightened oxidative damage. Andrographolide effectively reduced lung cellular infiltrates and decreased lung levels of TNF-α, IL-1β, CXCL1/KC, 8-OHdG, matrix metalloproteinase-8 (MMP-8), and MMP-9. The protective actions of andrographolide on CS-predisposed NTHi inflammation might be attributable to increased nuclear factor erythroid-2-related factor 2 (Nrf2) activation and decreased Kelch-like ECH-associated protein 1 (Keap1) repressor function, resulting in enhanced gene expression of antioxidant enzymes including heme oxygenase-1 (HO-1), glutathione reductase (GR), glutathione peroxidase-2 (GPx-2), glutamate-cysteine ligase modifier (GCLM), and NAD(P)H quinone oxidoreductase 1 (NQO1). Taken together, these findings strongly support a therapeutic potential for andrographolide in preventing lung inflammation caused by NTHi in cigarette smokers.
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System , 16 Medical Drive, Singapore 117600.
W S Daniel
WS
Tan
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System , 16 Medical Drive, Singapore 117600.
Hong Yong
HY
Peh
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System , 16 Medical Drive, Singapore 117600.
Wupeng
W
Liao
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System , 16 Medical Drive, Singapore 117600.
Chu Hui
CH
Pang
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System , 16 Medical Drive, Singapore 117600.|Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research and Technology (SMART) , 1 CREATE Way, Singapore 138602.
Tze Khee
TK
Chan
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System , 5 Science Drive 2, Singapore 117545.
Suk Hiang
SH
Lau
Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research and Technology (SMART) , 1 CREATE Way, Singapore 138602.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Health System , 5 Science Drive 2, Singapore 117545.
Vincent T
VT
Chow
Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System , 16 Medical Drive, Singapore 117600.|Immunology Program, Life Science Institute, National University of Singapore , 28 Medical Drive, Singapore 117456.
W S Fred
WS
Wong
D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D006192:Haemophilus Infections / Q000188:drug therapy; D006193:Haemophilus influenzae / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D020784:Matrix Metalloproteinase 8 / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry*; D011014:Pneumonia / Q000517:prevention & control; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004224:Diterpenes; D014409:Tumor Necrosis Factor-alpha; C030419:andrographolide; D051547:Heme Oxygenase-1; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase