Preventive Effect and Mechanism of Crossostephium chinense Extract on Balloon Angioplasty-Induced Neointimal Hyperplasia

Abstract

Balloon angioplasty-induced neointimal hyperplasia remains a clinical problem that must be resolved. The bioactivities of the Crossostephium chinense extract (CCE) have demonstrated potential in preventing the progression of restenosis. The present study evaluated whether CCE can suppress balloon angioplasty-induced neointima formation and elucidated its possible pharmacological mechanisms. A rat model of carotid arterial balloon angioplasty was established to evaluate the inhibitory effect of CCEs on neointimal hyperplasia. Two cell lines, A10 vascular smooth muscle cells (VSMCs) and RAW264.7 macrophages, were used to investigate the potential regulatory activities and pharmacological mechanisms of CCEs in cell proliferation and migration and in inflammation. Our in vitro results indicated that CCE3, the ethanolic extract of C. chinense, exerted the strongest growth inhibitory and antimigratory effects on VSMCs. CCE3 blocked the activation of focal adhesion kinase, platelet-derived growth factor receptor-β (PDGFRB), and its downstream molecules (AKT and mTOR) and reduced the expression of matrix metalloproteinase-2. In addition, our findings revealed that CCE3 significantly increased the expression of miRNA-132, an inhibitory regulator of inflammation and restenosis, and suppressed the expression of inflammation-related molecules (inducible nitric oxide synthase, cyclooxygenase-2, interleukin- (IL-) 1β, and IL-6). Our in vivo study results indicated that balloon injury-induced neointimal hyperplasia was inhibited by CCE3. CCE3 could reduce neointima formation in balloon-injured arteries, and this effect may be partially attributed to the CCE3-induced suppression of PDGFRB-mediated downstream pathways and inflammation-related molecules.

Two New Cytotoxic Sesquiterpene-Amino Acid Conjugates and a Coumarin-Glucoside from Crossostephium chinense

“…The whole plants of C. chinense are traditionally used for the treatment of diabetes and arthritis in southward China [ 2 ]. The extract has been reported to have various activities, such as preventing the progression of restenosis [ 3 ], inhibiting differentiation, formation and bone resorptive abilities of osteoclasts [ 4 ], and larvicidal activity [ 5 ]. Flavonoids [ 6 , 7 ], coumarin [ 2 , 8 ], sesquiterpene [ 2 ], and triterpenoid [ 9 ] have previously been isolated from C. chinense ; however, the phytochemical analysis is still insufficient, and a detailed evaluation of biological activities, especially for anticancer and antiparasitic activities, has yet to be conducted.…”

Ascophyllum nodosum and Fucus vesiculosus ameliorate restenosis via improving inflammation and regulating the PTEN/PI3K/AKT signaling pathway

“…For the wound healing and transwell methods, procedures were done as reported previously [44] . Briefly, A10 cells (5 × 10 4 cells/well) were seeded on 6-well plates, and allowed to grow to about 80% confluent.…”

“…Immunoblotting was carried out as previously illustrated with little adjustments [44] . Briefly, protein extraction from cells was carried out using the iNtRON PROPREP protein extraction solution (Korea).…”

“…Once inside, the catheter's balloon was inflated under pressure (1.3 kg/cm 2 ), pushed and pulled thrice, to ensure damage of the arterial wall. SE was administered by oral gavage three weeks prior to balloon injury to 2 weeks' post injury [44] . At the end of the study, blood and fecal samples were collected prior to sacrifice.…”