RESUMEN
BACKGROUND: Apigenin can reduce cardiomyocyte hypertrophy by downregulating hypoxia inducible factor-1 alpha (HIF-1α) expression. However, its effects on cardiac fibroblasts (CFs) and its exact inhibitory molecular mechanisms on HIF-1α remain unclear. PURPOSE: This study aims to examine the effects of apigenin on cell proliferation and differentiation, microRNA-122-5p (miR-122-5p) expression, and HIF-1α-mediated Smad signaling pathway in transforming growth factor beta 1 (TGF-ß1)-stimulated CFs and cardiac fibrosis and to investigate the relationship between miR-122-5p and HIF-1α. METHODS: The TGF-ß1-stimulated CFs, the combination of TGF-ß1-stimulated and miR-122-5p mimic-transfected CFs, the combination of TGF-ß1-stimulated and miR-122-5p inhibitor-transfected CFs, and the isoproterenol-induced cardiac fibrotic mice were used and treated with or without apigenin. The recombinant lentiviruses overexpressing HIF-1α vector and miR-122-5p mimic were co-transfected to observe their interaction. Related mRNA and protein expressions and myocardial collagen were determined. The luciferase reporter gene that contains HIF-1α wild type or mutant type 3'-UTR was used, and the luciferase activity was determined to verify the direct link between miR-122-5p and HIF-1α. RESULTS: In the TGF-ß1-stimulated CFs, apigenin treatment increased the miR-122-5p and Smad7 expressions and decreased the HIF-1α, α-smooth muscle actin, collagen â /â ¢, Smad2/3, and p-Smad2/3 expressions. Similar and inverse results were observed in the miR-122-5p mimic- and inhibitor-transfected CFs, respectively. Moreover, the miR-122-5p mimic could antagonize the effects of TGF-ß1 in the TGF-ß1 and miR-122-5p mimic-combined CFs, and the miR-122-5p inhibitor could enhance the effects of TGF-ß1 in the TGF-ß1 and miR-122-5p inhibitor-combined CFs. In the two aforementioned cell models, the addition of apigenin could further enhance the effects of miR-122-5p mimic and partially reverse the effects of miR-122-5p inhibitor. After treatment of HIF-1α-transfected CFs with miR-122-5p mimic, the HIF-1α expression decreased. Further study confirmed that HIF-1α was a direct target of miR-122-5p. Apigenin also decreased the myocardial collagen accumulation in cardiac fibrotic mice. CONCLUSION: Apigenin could suppress the differentiation and collagen synthesis of TGF-ß1-stimulated CFs and mouse cardiac fibrosis, and its mechanisms were related to the increment of miR-122-5p expression and subsequent downregulation of HIF-1α expression via direct interaction, which might finally result in the decrements of Smad2/3 and p-Smad2/3 expressions and increment of Smad7 expression.
Asunto(s)
Apigenina/farmacología , Colágeno/biosíntesis , Fibroblastos/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , MicroARNs/genética , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Colágeno/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibrosis , Regulación de la Expresión Génica/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Ratones Endogámicos ICR , Miocardio/citología , Miocardio/patología , Proteínas Smad/genética , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
<p><b>OBJECTIVE</b>To investigate the effects of Qushuanling Capsule ( QSLC) on thrombus formation and platelet aggregation in rats.</p><p><b>METHODS</b>Arteriovenous bypass, venous thrombosis, and middle cerebral artery thrombosis models were used in rats to investigate the anti-thrombotic effects of QSLC, a compound of nine Chinese herbs. The platelet aggregation induced by adenosine diphosphate (ADP), thrombin or arachidonic acid (AA), as well as the contents of thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F1α (6-keto-PGF1α) in rat plasma and aortic walls, were determined to investigate the possible mechanisms of the anti-thrombotic effects of QSLC.</p><p><b>RESULTS</b>After oral administration with QSLC for 7 days, arteriovenous bypass thrombosis was obviously suppressed compared with the model group, venous thrombosis was also obviously suppressed, rat behaviors were obviously improved, and brain infarct size as well as water content were also reduced. The platelet aggregation induced by ADP or thrombin was inhibited by QSLC, but the drug had no effect on AA-induced platelet aggregation and content of TXB(2) and 6-keto-PGF1α in plasma and the aortic wall.</p><p><b>CONCLUSION</b>These results suggest that QSLC can be used in the prevention and treatment of thrombotic diseases, and that its mechanism of action may be related to inhibition of platelet aggregation.</p>
Asunto(s)
Animales , Masculino , Ratas , 6-Cetoprostaglandina F1 alfa , Sangre , Adenosina Difosfato , Farmacología , Aorta , Metabolismo , Patología , Infarto Cerebral , Sangre , Quimioterapia , Patología , Medicamentos Herbarios Chinos , Farmacología , Usos Terapéuticos , Arteria Cerebral Media , Patología , Agregación Plaquetaria , Ratas Sprague-Dawley , Trombosis , Quimioterapia , Patología , Tromboxano B2 , Sangre , Trombosis de la Vena , Quimioterapia , PatologíaRESUMEN
<p><b>OBJECTIVE</b>To study the effect of Xiaoyu Tablet (XYT) on blood flow parameters and morphology of carotid artery in atherosclerotic patients.</p><p><b>METHODS</b>Using color Doppler ultrasonographic technique to examine the blood flow parameters and intimal thickness of carotid artery in 20 patients of carotid atherosclerosis after 24 weeks treatment of XYT, and compared with those in 10 patients treated with gastrodine lipid-lowering tablet.</p><p><b>RESULTS</b>After 24 weeks treatment, blood flow parameters of carotid artery were obviously improved and intimal thickness of common carotid arteries in both side was markedly decreased. XYT showed an effect better than that of gastrodine lipid-lowering tablet.</p><p><b>CONCLUSION</b>XYT is effective in increasing blood flow of cervical and cerebral arteries.</p>