title: Arborinane Triterpenoids from Rubia philippinensis Inhibit Proliferation and Migration of Vascular Smooth Muscle Cells Induced by the Platelet-Derived Growth Factor.
abstract: The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are associated with cardiovascular diseases and related complications. Such deleterious proliferation and migration events are triggered by cytokines and growth factors, and among them, platelet-derived growth factor (PDGF) is recognized as the most potent inducer. Despite the genus Rubia being researched to identify valuable commercial and medicinal virtues, Rubia philippinensis has rarely been investigated. Nine arborinane-type triterpenoids (1-9) were identified from this underutilized plant species. In particular, 4 was identified as the first arborinane derivative carrying a ketocarbonyl motif at C-19. The presence of the cyclopentanone moiety and the associated configurational assignment were determined by utilizing NOE and coupling constant analysis. These compounds were assessed for their inhibitory potential on PDGF-induced proliferation and the migration of VSMCs. Treatment with 5 μM compound 5 (62.6 ± 10.7%) and compound 9 (41.1 ± 4.7%) impeded PDGF-stimulated proliferation without exerting cytotoxicity. Compound 7 exhibited antimigration activity in a dose-dependent manner (38.5 ± 3.0% at 10 μM, 57.6 ± 3.2% at 30 μM). These results suggest that the arborinane-type triterpenoids may be a pertinent starting point for the development of cardiovascular drugs capable of preventing the intimal accumulation of VSMCs.
authors.affiliation: Department of Pharmaceutical Analysis and Standardization, National Institute of Medicinal Materials , Hanoi, Vietnam.
authors.forename: Khong Trong
authors.initials: KT
authors.lastname: Quan
authors.forename: Hyun-Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.|Chemical Biology Institute, Yale University , New Haven, Connecticut 06516, United States.
authors.forename: Joonseok
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Chemistry, Yale University , New Haven, Connecticut 06520, United States.|Chemical Biology Institute, Yale University , New Haven, Connecticut 06516, United States.
authors.forename: Hyun Bong
authors.initials: HB
authors.lastname: Park
authors.affiliation: Department of BioMolecular Sciences, Division of Pharmacognosy, and Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi , University, Mississippi 38677, United States.
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: Institute of Drug Research & Development, Chungnam National University , Daejeon 34134, Republic of Korea.
authors.forename: Chang-Seon
authors.initials: CS
authors.lastname: Myung
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D008297:Male; D015394:Molecular Structure; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D045470:Rubia / Q000737:chemistry*; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014744:Vietnam
chemical_list: D010982:Platelet-Derived Growth Factor; D014315:Triterpenes