Ginkgolide B functions as a determinant constituent of Ginkgolides in alleviating lipopolysaccharide-induced lung injury.
Ginkgolides are the major bioactive components of Ginkgo biloba extracts, however, the exact constituents of Ginkgolides contributing to their pharmacological effects remain unknown. Herein, we have determined the anti-inflammatory effects of Ginkgolide B (GB) and Ginkgolides mixture (GM) at equivalent dosages against lipopolysaccharide (LPS)-induced inflammation. RAW 264.7 cell culture model and mouse model of LPS-induced lung injury were used to evaluate in vitro and in vivo effects of GB and GM, respectively. In RAW 264.7 cells, GB and GM at equivalent dosages exhibit an identical capacity to attenuate LPS-induced inducible nitric oxide synthase mRNA and protein expression and subsequent NO production. Likewise, GB and GM possess almost the same potency in attenuating LPS-induced expression and activation of nuclear factor kappa B (p65) and subsequent increases in tumor necrosis factor-α mRNA levels. In LPS-induced pulmonary injury, GB and GM at the equivalent dosages have equal efficiency in attenuating the accumulation of inflammatory cells, including neutrophils, lymphocytes, and macrophages, and in improving the histological damage of lungs. Moreover, GB and GM at equivalent dosages decrease the exudation of plasma protein to the same degree, whereas GM is superior to GB in alleviating myeloperoxidase activities. Finally, though GB and GM at equivalent dosages appear to reduce LPS-induced IL-1β mRNA and protein levels and IL-10 protein levels to the same degree, GM is more potent than GB to attenuate the IL-10 mRNA levels. Taken together, this study demonstrates that GB functions as the determinant constituent of Ginkgolides in alleviating LPS-induced lung injury.
Department of paediatrics, The First People's Hospital of Wenling City, Wenling City 317500, China; Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou City 310058, China.
Fugen
F
Wu
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou City 310058, China.
Wei
W
Shi
Technological Center of China Tobacco Zhejiang Industrial Co., LTD, Hangzhou 310024, China.
Guojun
G
Zhou
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou City 310058, China.
Hongyi
H
Yao
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou City 310058, China.
Chengyun
C
Xu
Technological Center of China Tobacco Zhejiang Industrial Co., LTD, Hangzhou 310024, China.
Weiqiang
W
Xiao
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou City 310058, China.
Junsong
J
Wu
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou City 310058, China. Electronic address: xiwu@zju.edu.cn.
Ximei
X
Wu
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D005260:Female; D046934:Ginkgolides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D009195:Peroxidase / Q000378:metabolism; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects
D046934:Ginkgolides; D053583:Interleukin-1beta; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D016753:Interleukin-10; D009569:Nitric Oxide; C045856:ginkgolide B; D009195:Peroxidase
Ginkgolide B; Ginkgolides; Lipopolysaccharides; Lung injury