Back to Search
Start Over
The effects of wild bitter gourd fruit extracts on ICAM-1 expression in pulmonary epithelial cells of C57BL/6J mice and microRNA-221/222 knockout mice: Involvement of the miR-221/-222/PI3K/AKT/NF-κB pathway
The effects of wild bitter gourd fruit extracts on ICAM-1 expression in pulmonary epithelial cells of C57BL/6J mice and microRNA-221/222 knockout mice: Involvement of the miR-221/-222/PI3K/AKT/NF-κB pathway
- Source :
- Phytomedicine. 42:90-99
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Background The extracts from wild bitter gourd fruit (WBGE) were reported to possess numerous pharmacological activities. However, the anti-inflammatory effects of WBGE on human lung epithelial cells and the underlying mechanisms have not been determined. Purpose To evaluate the molecular basis of the effects of WBGE on intercellular adhesion molecule-1 (ICAM-1) expression in alveolar epithelial (A549) cells, C57BL/6 wild-type (WT) mice and microRNA (miR)-221/-222 knockout (KO) mice with or without tumor necrosis factor (TNF-α; 3 ng/ml) treatment. Study design/methods WT mice and miR-221/-222 KO mice were fed a control diet and divided into four groups (C: control mice; T: treated with TNF-α alone; WBGE/T: pretreated with WBGE and then stimulated with TNF-α; WBGE: treated with WBGE alone). The effects of WBGE on ICAM-1 expression and the related signals in A549 cells and mice with or without TNF-α treatment were examined by Western blot and immunofluorescent staining. Results WBGE significantly decreased the TNF-α-induced ICAM-1 expression in A549 cells through the inhibition of phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT)/ nuclear factor- kappa B (NF-κB)/ inhibitor of NF-κB (IκB) phosphorylation and decreased leukocyte adhesion. In addition, WBGE reduced endogenous ICAM-1 expression and upregulated miR-221/-222 expression. The overexpression of miR-222 decreased PI3K/AKT/NF-κB/IκB and ICAM-1 expression, which resulted in reducing monocyte adhesion. Moreover, WBGE reduced ICAM-1 expression in lung tissues of WT mice with or without TNF-α treatment and upregulated miR-221/222. WBGE did not affect the miR-221/-222 level and had little effect on ICAM-1 expression in miR-221/-222 KO mice. Conclusions These results suggest that WBGE reduced ICAM-1 expression both under in vitro and in vivo conditions. The protective effects were mediated partly through the miR-221/-222/PI3K/AKT/NF-κB pathway.
- Subjects :
- 0301 basic medicine
Momordica charantia
Bitter gourd
Pharmaceutical Science
Phosphatidylinositol 3-Kinases
03 medical and health sciences
Western blot
Drug Discovery
Cell Adhesion
medicine
Animals
Humans
Lung
Protein kinase B
PI3K/AKT/mTOR pathway
Mice, Knockout
Pharmacology
A549 cell
ICAM-1
medicine.diagnostic_test
Plant Extracts
Tumor Necrosis Factor-alpha
Chemistry
Anti-Inflammatory Agents, Non-Steroidal
NF-kappa B
Epithelial Cells
Intercellular Adhesion Molecule-1
Molecular biology
Mice, Inbred C57BL
MicroRNAs
030104 developmental biology
Complementary and alternative medicine
Fruit
Knockout mouse
Molecular Medicine
Tumor necrosis factor alpha
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 09447113
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- Phytomedicine
- Accession number :
- edsair.doi.dedup.....a1c3d253ee6aac617ce3deb53dc6f91f
- Full Text :
- https://doi.org/10.1016/j.phymed.2018.03.023