RESUMEN
The pathological mechanism of restenosis is primarily attributed to excessive proliferation of vascular smooth muscle cells (VSMC). The preventive effects of ethanol extract of Dunaliella salina (EDS) on balloon injury-induced neointimal formation were investigated. To explore its molecular mechanism in regulating cell proliferation, we first showed that EDS markedly reduced the human aortic smooth muscle cell proliferation via the inhibition of 5'-bromo-2'-deoxyuridine (BrdU) incorporation at 40 and 80 microg/ml. This was further supported by the G0/G1-phase arrest using a flow cytometric analysis. In an in vivo study, EDS at 40 and 80 microg/ml was previously administered to the Sprague-Dawley rats and found that the thickness of neointima, and the ratio of neointima:media were also reduced. EDS inhibited VSMC proliferation in a dose-dependent manner following stimulation of VSMC cultures with 15 % fetal bovine serum (FBS). Suppressed by EDS were 15 % FBS-stimulated intracellular Raf, phosphorylated extracellular signal-regulated kinases (p-Erk) involved in cell-cycle arrest and proliferating cell nuclear antigen. Phosphorylated focal adhesion kinase (p-FAK) was also suppressed by EDS. Also active caspase-9, caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP) protein expression levels were increased by administration with EDS; the apoptotic pathway may play an important role in the regulatory effects of EDS on cell growth. These observations provide a mechanism of EDS in attenuating cell proliferation, thus as a potential intervention for restenosis.
Asunto(s)
Fármacos Cardiovasculares/farmacología , Chlorophyta , Miocitos del Músculo Liso/efectos de los fármacos , Extractos Vegetales/farmacología , Túnica Íntima/efectos de los fármacos , Angioplastia de Balón , Animales , Aorta/lesiones , Bromodesoxiuridina/antagonistas & inhibidores , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Bovinos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Citometría de Flujo , Humanos , Interfase , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Poli Adenosina Difosfato Ribosa/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas , Ratas Sprague-Dawley , Túnica Íntima/metabolismo , Túnica Íntima/patologíaRESUMEN
AIMS OF THE STUDY: This study investigated the analgesic and anti-inflammatory effects of a water extract of Trachelospermum jasminoides (WET) in ICR mice. MATERIALS AND METHODS: In HPLC analysis, the fingerprint chromatogram of WET was established. Acetic acid-induced writhing response and formalin-induced pain were examined the analgesics effects of WET. WET on lambda-Carrageenan(carr)-induced paw edema was performed. We investigate the anti-inflammatory mechanism of WET via studies of the activities of glutathione peroxidase (GPx), glutathione reductase (GRx) in the liver and the levels of malondialdehyde (MDA) and nitrite oxide (NO) in the edema paw. Serum NO and TNF-alpha were also measured. RESULTS: The fingerprint chromatogram of WET was established through HPLC analysis, and implies that WET contains the active ingredient gallic acid, chlorgenic acid, caffeic acid, taxifolin, isoquercitrin and quercetin. WET significantly inhibited the numbers of acetic acid-induced writhing responses and the formalin-induced pain in the late phase. In the anti-inflammatory test, WET inhibited the development of paw edema induced by carr. WET decreased the paw edema at the third, fourth and fifth hour after carr administration, and increased the activities of SOD, GPx and GRx in the liver tissue and decreased the MDA level in the edema paw at the third hour after carr injection. WET decreased the level of NO in edematous paw tissue and in serum level, and diminished the level of serum TNF-alpha at the fifth hour after carr injection. CONCLUSIONS: These results demonstrated that WET is an effective anti-inflammatory agent in carr-induced inflammation. WET probably exerts anti-inflammatory effects by suppressing TNF-alpha and NO. The anti-inflammatory mechanism of WET might be related to the decrease in the level of MDA in the edema paw via increasing the activities of SOD, GPx and GRx in the liver.