Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-κB pathway.
The purpose of this study was to investigate the protective effect of PD against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its potential mechanism. In vivo, PD and dexamethasone were intraperitoneally administered 1h before LPS stimulation. Then, mice were sacrificed at 6h post-LPS stimulation. Neutrophil number, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) were determined, as well as lung wet to dry ratio (W/D) and polymorphonuclear (MPO) activity. The protein expressions of Toll like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), IL-1R-associated kinases 1 (IRAK1), IRAK4, inhibitor of nuclear factor kappa-B kinase (IKK)α, p-IKKα, IKKβ, p-IKKβ, inhibitor of NF-κB (IκBα), p-IκBα and NF-κB in lung tissues were assessed. Besides, we detected the IL-6, IL-1β, IL-8, TNF-α levels and TLR4, MyD88, NF-κB protein expressions in LPS-induced BEAS-2B cells. Consequently, PD significantly inhibited the levels of W/D, MPO, neutrophils number, TNF-α, IL-6, IL-1β and reversed TLR4-MyD88-NF-κB signaling pathway in lung tissues. In vitro assays, PD effectively negatively mediated the inflammatory cytokines and ameliorated the high expressions of TLR4, MyD88, NF-κB caused by LPS simulation in Human bronchial epithelial BEAS-2B cells. This study indicated that PD played a protective role in LPS-induced ALI and BEAS-2B cells. The results supported further study of PD as potential candidate for acute lung injury.
School of Pharmacy, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China.
Qi
Q
Jiang
Orthopedic Surgery Department, West China Hospital, Sichuan University, No.37 Guoxuexiang, Chengdu 610041, China.
Min
M
Yi
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China.
Qianqian
Q
Guo
School of Pharmacy, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China.
Ciman
C
Wang
School of Pharmacy, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China.
Huimin
H
Wang
Department of Respiratory Medicine, The Second Hospital of Jilin University, Changchun, 130041, China.
Shanshan
S
Meng
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China.
Chao
C
Liu
The Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu 322000, China.
Yeliu
Y
Fu
School of Pharmacy, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: huijicpu@163.com.
Hui
H
Ji
School of Pharmacy, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: tongchencpu@163.com.
Tong
T
Chen
D055371:Acute Lung Injury / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005960:Glucosides / Q000627:therapeutic use*; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88 / Q000187:drug effects*; D016328:NF-kappa B / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000627:therapeutic use*; D051197:Toll-Like Receptor 4 / Q000187:drug effects*
D016207:Cytokines; D005960:Glucosides; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D013267:Stilbenes; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C058229:polydatin
ALI; BEAS-2B cells; Cytokines; LPS; Polydatin; TLR4-MyD88-NF-κB pathway