Whitmania Pigra Whitman Extracts Inhibit Lipopolysaccharide Induced Rat Vascular Smooth Muscle Cells Migration and their Adhesion Ability to THP-1 and RAW 264.7 Cells.
OBJECTIVE
Atherosclerosis is a kind of chronic inflammatory disease. A crucial pathology change of atherosclerosis is the migration of activated VSMCs to the intima where they interact with leukocytes by expressing adhesion molecules, including intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Moreover, monocyte chemoattractant protein-1 (MCP-1) expressed by VSMCs plays an important role in recruiting monocytes and macrophages. Leech (Whitmania pigra Whitman) is a traditional Chinese medicine to treat cardiovascular diseases including atherosclerosis, however previous research has rarely reported the molecular mechanism for its curative effect. Thus, our study focuses on the effects of leech extracts on the expression of inflammatory factors, adhesion molecules and MCP-1 in rat VSMCs.


METHODS
In our present study, wound-healing assay and Boyden chamber model were applied to evaluate the anti-migration effect of LEE (Leech Enzyme Extracts) on LPS induced VSMCs. The anti-adhesion effect was assessed using DiI-labeled THP-1 and RAW264.7.


RESULTS
LEE suppressed LPS-induced VSMCs migration and decreased the chemotaxis and adhesive capacity of THP-1 and RAW264.7 to LPS-stimulated VSMCs. LEE also attenuated the upregulation of a variety of pro-atherosclerotic factors by inhibiting the phosphorylation of p38 MAPK. LEE was also observed to prevent NF-κB p65 nuclear localization using immune-fluorescent staining.


CONCLUSIONS
In conclusion, LEE suppresses LPS-induced upregulation of inflammatory factors, adhesion molecules and MCP-1 in rat VSMCs mainly via inhibiting the p38 MAPK/NF-κB pathways, thus partly uncovered LEE's molecular mechanisms for its therapeutic effect on atherosclerosis.
Marine College, Shandong University.
Shuaishuai
S
Li
Long
L
Cheng
Dengkun
D
An
Shuliang
S
Song
Hao
H
Liang
Fulong
F
Chu
Aiguo
A
Ji
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007865:Leeches / Q000201:enzymology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
D005343:Fibrinolytic Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger