Assuntos
Atorvastatina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Schisandra , Animais , Atorvastatina/sangue , Citocromo P-450 CYP3A/fisiologia , Dieta Hiperlipídica , Masculino , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fitoterapia , Ratos , Ratos Sprague-DawleyRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Salviae Miltiorrhizae Radix (Danshen) and Puerariae Lobatae Radix (Gegen) are principal herbs have long been used in combination for treating cardiovascular disease. AIMS OF STUDY: Danshen and Gegen in the ratio of 7:3 (DGW) have significantly reduced the carotid intimal-media thickening (IMT) in patients in our previous clinical study. In the present study, we have demonstrated the mechanisms on IMT reduction by investigating its key processes on both vascular smooth muscle cell (vSMC) and endothelial cells. MATERIALS AND METHODS: The anti-proliferative effects of DGW on platelet-derived growth factor (PDGF) induced vSMC proliferation were studied by cell proliferation, cell cycle distribution, p-ERK and cyclin D expression level. The anti-migratory effect of DGW was investigated by using transwell apparatus. For human umbilical endothelial cells (HUVEC), the inhibitory effects of DGW on TNF-alpha induced cell adhesion, cell adhesion molecules expression, MCP-1 and IL-6 production were investigated. RESULTS: DGW significantly inhibited A7r5 proliferation and exhibited G1/S cell cycle arrest by suppressing both p-ERK and cyclin D expression. Moreover, DGW showed anti-migratory effect against PDGF-induced A7r5 migration. In addition, DGW inhibited the cell adhesion as well as the expression of ICAM-1 and VCAM-1, the production of MCP-1 but not IL-6 in TNF-α stimulated HUVECs. CONCLUSIONS: Our study provided strong scientific evidence on IMT reduction in patients by modulating the key atherogenic events in both vSMC and endothelial cells.
Assuntos
Aterosclerose/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Endotélio Vascular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Fitoterapia , Pueraria , Salvia miltiorrhiza , Aterosclerose/metabolismo , Fenômenos Fisiológicos Celulares/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Ciclina D/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Raízes de Plantas , Túnica Íntima/citologia , Túnica Íntima/efeitos dos fármacos , Túnica Íntima/metabolismo , Túnica Média/citologia , Túnica Média/efeitos dos fármacos , Túnica Média/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Radix Salviae miltiorrhizae (Danshen) and Radix Puerariae lobatae (Gegen) have long been used in traditional Chinese Medicine and serve as the principal herbs in treating cardiovascular disease. AIMS OF THE STUDY: In the present study, an aqueous extract comprising Danshen and Gegen in the ratio of 7:3 (DG) was investigated for its anti-hypertension in vivo and vasodilative activities ex vivo. MATERIALS AND METHODS: The anti-hypertensive effect of DG extract was investigated in spontaneously hypertensive rat (SHR) by measuring systolic blood pressure (SBP). Oral administration of DG extract was started at age of 6 weeks and 14 weeks for the preventive and therapeutic studies, respectively. Blood pressure was measured by tail-cuff method biweekly for 12 weeks. The ex vivo vasodilative activities of DG extract, its dependency on endothelium and the involvement of nitric oxide, prostacyclin and potassium channels were investigated using isolated rat aorta ring in organ bath. RESULTS: For in vivo study, systolic blood pressure was significantly reduced in DG extract-treated groups (90.2 and 300 mg/kg) as compared with the SHR control in both preventive and therapeutic studies. However, DG extract was unable to suppress or delay the onset of hypertension in the preventive study. For ex vivo study, the results showed that DG extract induced a concentration-dependent relaxation in aorta and persisted response was observed with the removal of endothelium. Besides, pretreatment with a non-selective potassium channel inhibitor tetraethylammonium (TEA) also significantly inhibited DG extract-induced vasodilation. Further investigations on specific potassium channel blockers revealed that ATP-sensitive potassium (K(ATP)) channel inhibitor glibenclamide, inward rectifier potassium (Kir) inhibitor barium chloride and voltage-dependent potassium (K(v)) channel inhibitor 4-aminopyridine, but not BK(Ca) channel inhibitor iberiotoxin, exerted significant inhibition on DG extract-induced vasodilation. CONCLUSIONS: The results of in vivo SHR animal model suggested that DG aqueous extract possessed blood pressure lowering effect on both pre- and post-hypertensive rats, which could be explained by its endothelium-independent vasodilation via the opening of K(ATP), Kir and K(v) channels.