Eriobotrya japonica leaf and its triterpenes inhibited lipopolysaccharide-induced cytokines and inducible enzyme production via the nuclear factor-kappaB signaling pathway in lung epithelial cells.
Pulmonary inflammation is a characteristic of many lung diseases. Increased levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines, such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and IL-8, have been correlated with lung inflammation. In this study, we used lipopolysaccharide (LPS) to induce iNOS, COX-2, and cytokines (TNF-alpha, IL-1beta, and IL-8) productions in human lung epithelial cells (A-549). Leaf of Eriobotrya japonica (Pi-Pa-Ye, PPY), a traditional Chinese medicine for the treatment of pulmonary inflammatory diseases, was capable of suppressing LPS-induced cytokine productions in a dose-dependent manner. Moreover, the suppression of PPY on the cytokine productions resulted from the inhibition of inhibitory kappaB-alpha phosphorylation and nuclear factor-kappaB (NF-kappaB) activation. Analysis of the anti-inflammatory effects of ursolic acid and oleanolic acid, the triterpene compounds present in PPY, showed that ursolic acid significantly inhibited LPS-induced IL-8 production, NF-kappaB activation, and iNOS mRNA expression, whereas oleanolic acid did not have these effects. In conclusion, our findings suggested the potential mechanisms of PPY and its active component, ursolic acid, in the treatment of pulmonary inflammation.
Lee
Chang-Hsien
CH
Graduate Institute of Chinese Medical Science, China Medical University, Taichung 40402, Taiwan.
Wu
Shih-Lu
SL
Chen
Jaw-Chyun
JC
Li
Chia-Cheng
CC
Lo
Hsin-Yi
HY
Cheng
Wen-Yu
WY
Lin
Jaung-Geng
JG
Chang
Yung-Hsien
YH
Hsiang
Chien-Yun
CY
Ho
Tin-Yun
TY
D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D031983:Eriobotrya / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D016328:NF-kappa B / Q000276:immunology*; D018515:Plant Leaves / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*
D016207:Cytokines; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014315:Triterpenes