Flavonoids from Radix Tetrastigmae improve LPS-induced acute lung injury via the TLR4/MD-2-mediated pathway.
Total flavonoids isolated from Radix Tetrastigmae (RTFs) possess immunomodulatory activity, particularly on inflammation. In mice with lipopolysaccharide (LPS)‑induced acute lung injury (ALI), treatment with RTFs at 40, 80 and 160 mg/kg significantly reduced leukocyte infiltration, improved histopathological changes in lung tissues and decreased the LPS‑induced production of several inflammatory mediators in the bronchoalveolar lavage fluid (BALF), which included the chemotatic factors, granulocyte colony‑stimulating factor, monocyte inflammatory protein‑1α and B‑lymphocyte colony inflammatory cytokines, including interleukin (IL)‑1β, IL‑6, IL‑12p40 and tumor necrosis factor‑α, in a dose‑dependent manner. In addition, the expression of the Toll‑like receptor 4 (TLR4)/myeloid differentiation factor‑2 (MD‑2) compound, the phosphorylation of p38 mitogen‑activated protein kinase (p38MAPK), c‑Jun N‑terminal kinase (JNK) and nuclear transcription factor‑κB (NF‑κB), in addition to the DNA binding activity of NF‑κB p65 in lung tissues, were all attenuated following RTF treatment. However, RTF treatment had no effect on extracellular signal‑regulated kinase (ERK). In conclusion, RTFs contributed to the regulation of LPS‑induced ALI through the TLR4/MD-2-mediated NF‑κB, JNK and p38MAPK pathways. This may be a potential therapeutic option for the treatment of inflammatory diseases.
Department of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
Dan-Dan
DD
Liu
Department of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
Gang
G
Cao
Pathological Department, People's Hospital of Zhejiang, Hangzhou, Zhejiang 310046, P.R. China.
Li-Kai
LK
Han
Department of Basic Medicine, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China.
Yi-Lu
YL
Ye
Department of Basic Medicine, Zhejiang Medical College, Hangzhou, Zhejiang 310053, P.R. China.
Qi
Q
Zhang
Hangzhou Xuejun High School, Hangzhou, Zhejiang 310012, P.R. China.
Yu-Han
YH
Sima
Department of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.
Wei-Hong
WH
Ge
D055371:Acute Lung Injury / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression; D018836:Inflammation Mediators / Q000097:blood; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000009:adverse effects*; D051218:Lymphocyte Antigen 96 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; D051197:Toll-Like Receptor 4