Journal List > Korean J Physiol Pharmacol > v.13(2) > 1025588

Choi, Park, Lee, Lee, Won, Kim, Lee, and Kim: Olibanum Extract Inhibits Vascular Smooth Muscle Cell Migration and Proliferation in Response to Platelet-Derived Growth Factor

Abstract

Olibanum (Boswellia serrata) has been shown to have anti-inflammatory, anti-arthritic and anti-cancer effects. This study determined the role of a water extract of olibanum in platelet-derived growth factor (PDGF)-stimulated proliferation and migration of rat aortic smooth muscle cells (RASMCs). PDGF-BB induced the migration and proliferation of RASMCs that were inhibited by olibanum extract in a dose-dependent manner. The PDGF-BB-increased phosphorylation of p38 mitogen-activated protein kinase (MAPK); the heat shock protein (Hsp) 27 was significantly inhibited by the olibanum extract. The effects of PDGF-BB-induced extracellular signal-regulated kinase1/2 was not altered by the olibanum extract. Treatment with olibanum extract inhibited PDGF-BB-stimulated sprout out growth of aortic rings. These results suggest that the water extract of olibanum inhibits PDGF-BB-stimulated migration and proliferation in RASMCs as well as sprout out growth, which may be mediated by the inhibition of the p38 MAPK and Hsp27 pathways.

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Fig. 1.
Effect of olibanum extract on PDGF-BB-stimulated RASMC migration. The effect of olibanum extract on RASMC migration. The cells from SD rats were treated with or without olibanum extract (1~1,000 μg/ml) or PDGF-BB (10 ng/ml) for 90 min. Migration was quantified using a Boyden chamber assay as described in the Methods section. Cell migration in the quiescent state was expressed as 100% (n=8). Each value represents the mean±SEM. ∗Denotes a significant difference from the PDGF-BB-stimulated state, with p<0.05.
kjpp-13-107f1.tif
Fig. 2.
Effect of olibanum extract on PDGF-BB-stimulated RASMC proliferation. Cells were treated with or without olibanum extract (1~1,000 μg/ml) and then stimulated by PDGF-BB (10 ng/ml) for 36 h. Cell proliferation was examined with the BrdU incorporation assay. Proliferation in the quiescent state was considered as 100% (n=10). Each value represents the mean±SEM. ∗Significant differences from responses in the PDGF-BB-stimulated state, with p<0.05.
kjpp-13-107f2.tif
Fig. 3.
Effects of olibanum extract on activity of MAPK in RASMCs. After cells were treated without or with olibanum extract (1 ~ 1,000 μg/ml) for 30 min, cells were stimulated with PDGF-BB (10 ng/ml) for 10 min. The RASMC lysates were immunoblotted with antibodies. The phosphorylation of p38 MAPK and ERK1/2 was examined using phosphor-specific antibodies. The total expression of kinases and β-actin was measured using non-phospho-specific antibodies and anti-β-actin antibody, respectively. (B, C) Statistical analysis of the phosphorylation level of MAPKs obtained in (A). The basal levels of phosphorylation are considered as 100% (n=4). Each value represents the mean±SEM. ∗Significant differences from the PDGF-BB-stimulated state, with p<0.05. p-p38, phosphorylated p38 MAPK; p-ERK1/2, phosphorylated ERK1/2.
kjpp-13-107f3.tif
Fig. 4.
Effect of olibanum extract on PDGF-BB-induced phosphorylation of Hsp27 in RASMCs. The phosphorylation of Hsp27 was examined using a phospho-specific antibody. (B) Statistical analysis of the phosphorylation level of Hsp27 obtained in (A). The basal levels of phosphorylation are considered as 100% (n=4). Each value represents the mean±SEM. ∗Significant differences from the PDGF-BB-stimulated state, with p<0.05. p-Hsp27, phosphorylated Hsp27.
kjpp-13-107f4.tif
Fig. 5.
Ex vivo analysis of olibanum extract on sprout formation of aortic rings in response to PDGF-BB. Aortic rings (1 mm) were embedded in Matrigel and cultured. Rings without any treatment (vehicle) and PDGF-BB (10 ng/ml) or olibanum extract (1~1,000 μg/ml)-treated rings. Results were obtained on day 5. (B) The statistical results obtained from panel (A). The level in vehicle (0.1% DMSO)- treated rings is expressed as 100% (n=4). Each value represents the mean±SEM. ∗Denotes a significant difference from the PDGF-BB (10 ng/ml)-stimulated state, with p<0.05.
kjpp-13-107f5.tif
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