title: Rosa hybrida extract suppresses vascular smooth muscle cell responses by the targeting of signaling pathways, cell cycle regulation and matrix metalloproteinase-9 expression.
abstract: The pharmacological effects of Rosa hybrida are well known in the cosmetics industry. However, the role of Rosa hybrida in cardiovascular biology had not previously been investigated, to the best of our knowledge. The aim of the present study was to elucidate the effect of water extract of Rosa hybrida (WERH) on platelet‑derived growth factor (PDGF)-stimulated vascular smooth muscle cells (VSMCs). VSMC proliferation, which was stimulated by PDGF, was inhibited in a non-toxic manner by WERH treatment, which also diminished the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and AKT. Treatment with WERH also induced G1-phase cell cycle arrest, which was due to the decreased expression of cyclins and cyclin-dependent kinases (CDKs), and induced p21WAF1 expression in PDGF-stimulated VSMCs. Moreover, WERH treatment suppressed the migration and invasion of VSMCs stimulated with PDGF. Treatment with WERH abolished the expression of matrix metalloproteinase-9 (MMP-9) and decreased the binding activity of nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and specificity protein 1 (Sp1) motifs in PDGF-stimulated VSMCs. WERH treatment inhibited the proliferation of PDGF‑stimulated VSMCs through p21WAF1‑mediated G1-phase cell cycle arrest, by decreasing the kinase activity of cyclin/CDK complexes. Furthermore, WERH suppressed the PDGF-induced phosphorylation of ERK1/2 and AKT in VSMCs. Finally, treatment with WERH impeded the migration and invasion of VSMCs stimulated by PDGF by downregulating MMP-9 expression and a reduction in NF-κB, AP-1 and Sp1 activity. These results provide new insights into the effects of WERH on PDGF-stimulated VSMCs, and we suggest that WERH has the potential to act as a novel agent for the prevention and/or treatment of vascular diseases.
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong-si, Gyeonggi-do 17546, Republic of Korea.
authors.forename: Se-Jung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong-si, Gyeonggi-do 17546, Republic of Korea.
authors.forename: Se Yeon
authors.initials: SY
authors.lastname: Won
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong-si, Gyeonggi-do 17546, Republic of Korea.
authors.forename: Sung Lyea
authors.initials: SL
authors.lastname: Park
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong-si, Gyeonggi-do 17546, Republic of Korea.
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Song
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong-si, Gyeonggi-do 17546, Republic of Korea.
authors.forename: Dae-Hwa
authors.initials: DH
authors.lastname: Noh
authors.affiliation: Graduate School of East-West Medical Science, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Hong-Man
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Acupuncture Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Chang Shik
authors.initials: CS
authors.lastname: Yin
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Food and Nutrition, Chung-Ang University, Anseong-si, Gyeonggi-do 17546, Republic of Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D027826:Rosa / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D010936:Plant Extracts; D010982:Platelet-Derived Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9