RESUMO
Abstract Ligustrazine is widely used for the treatment of cardiovascular diseases in traditional Chinese medication. It has been reported that Ligustrazine decreases the concentration of intracellular calcium ions (Ca2+); however, the underlying mechanism remains unknown. In the present study, the effect of Ligustrazine on adenosine diphosphate (ADP)-induced platelet aggregation was evaluated using a turbidimetric approach. The changes in concentration of intracellular Ca2+ stimulated by ADP was measured using fluo-4, a fluorescent Ca2+ indicator dye. The mRNA expression of stromal interaction molecule l (STIM1) and Orai1, calcium sensor, was determined using real-time PCR. In addition, the protein expression of STIM1, Orai1, and serum/glucocorticoid-regulated protein kinase 1 (SGK1) was determined using Western blot analysis. The data demonstrated that Ligustrazine significantly suppressed platelet aggregation in a dose-dependent manner and reduced the concentration of intracellular Ca2+ triggered by ADP. Our data showed that Ligustrazine treatment inhibited the expression of STIM1 and Orai1 induced by ADP at both mRNA and protein levels, and suppressed the protein expression of SGK1. Taken together, our data indicated that Ligustrazine suppressed platelet aggregation by partly inhibiting the activities of calcium sensors, thereby suggesting that Ligustrazine may be a promising candidate for the treatment of platelet aggregation.
Assuntos
Animais , Masculino , Ratos , Proteínas Quinases , Doenças Cardiovasculares/patologia , Agregação Plaquetária , Difosfato de Adenosina/farmacologia , Western Blotting/métodos , Cálcio/agonistas , Povo Asiático/classificação , Moléculas de Interação EstromalRESUMO
Abstract Xuezhikang (XZK) is an extract of Chinese red yeast rice. It has multiple protective effects in cardiovascular systems. However, the underlying mechanism by which XZK affects free fatty acid (FFA)-induced lipogenesis in hepatocellular steatosis model is still unknown. Herein, we investigated this mechanism in HepG2 cells. The HepG2 cells were treated with palmitate acid (PA) to induce lipogenesis. Then the PA-induced HepG2 cells were subsequently treated with XZK. After 24 h of treatment, we determined the intracellular triglyceride (TG) contents and average areas of lipid droplets. To study the involvement of AMPK signaling pathway, we pre-treated the PA-induced HepG2 cells with Compound C, an AMPK inhibitor, before XZK treatment. Expressions of p-AMPK and AMPK were determined by Western blot. The results showed that XZK decreased TG content and lipid accumulation in hepatocellular steatosis model. Compound C abolished the effects of XZK. These results demonstrated for the first time that XZK protects hepatocytes against lipid accumulation induced by free fatty acids. Its effects may be mediated by the activation of AMPK pathway.
Assuntos
Oryza/anatomia & histologia , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Lipídeos/efeitos adversos , Povo Asiático/classificação , Células Hep G2RESUMO
T0001 is the first mutant of etanercept with a higher affinity to tumor necrosis factor α (TNF-α) than etanercept. In order to investigate the safety and tolerability of T0001, a study was carried out in healthy Chinese subjects. A first-in-human, dose escalation study was conducted in healthy Chinese subjects. Fifty-six subjects were divided into six dose cohorts (10 mg, 20 mg, 35 mg, 50 mg, 65 mg and 75 mg) to receive a single subcutaneous injection of T0001. Safety and tolerability assessment were based on the records of vital signs, physical examinations, clinical laboratory tests, 12-lead electrocardiograms and adverse events (AEs). All subjects were in good compliance and none withdraw due to AEs. No serious AEs occurred. A total of twenty-three AEs in sixteen subjects were recorded, and eighteen of these AEs were believed to be related to T0001. The most frequently reported AEs were injection site reactions and white blood cell count increase. All these AEs were of mild to moderate intensity and most of them recovered spontaneously within 14 days. In this study, no dose-limiting toxicity was observed, and the maximum tolerated dose was identified as 75 mg. T0001 was considered safe and generally well tolerated at doses up to 75 mg in healthy Chinese volunteers
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Segurança , Voluntários , Dose Única/efeitos dos fármacos , Etanercepte/análogos & derivados , Exame Físico , Artrite Reumatoide/patologia , Fator de Necrose Tumoral alfa/classificação , Técnicas de Laboratório Clínico , Povo Asiático/classificação , Eletrocardiografia , Reação no Local da Injeção , Injeções Subcutâneas/classificaçãoRESUMO
1.Son innegables los rasgos fisonòticos que asemejan al autòcnono boliviano con los individuos de la raza mongòlica, 2.Se explica este paracido, teniendo encuenta las posibles vias de inmigraciòn sequidas por los primitivos hombres de Asìa que llegaron a Amèrica, 3.Se ha podido observar que los diametros transversal y vertical de la abertura palpebral de nuestros indìgenas estàn disminuidos con relaciòn al ojo europeo de la raza blanca, 4.Es de presumir que el pronunciado desrrollo del hueso malar,rasgos evidenciados en los habitantes de la raza altaica, determinaria la elevaciòn consiguiente de la epòfisis orbitaria externa del hueso frontal (causa tambien del ìndice orbitario tipo alto (7)) y consecuentemente tambièn la elevaciòn del ligamento palpebral externo que determinarìa la oblilcuidad de la abertura palpebral, 5.Tambièn tengo la impresiòn que los arcos superciliares bastante prominentes en gran parte de nuestros indìgenas determinaria que la piel del pàrpado superior libre de apoyo òseo ocasionarìa esa pseudoblefarochalasis, observada muy frecuentemente en los indìgenas aymaras y quechuas, 6.Aunque el motivo principal de este trabajo se refiere al aspecto exterior de la regìon palpebral y sum relaciòn con estructura anatòmicas vecinas, he señalado la frecuencia con que se observa el Pterigiòn que les bastante alta,y la coloraciòn morenuzca que se presenta en algunos casos en el globo ocular, èsta coloracioòn cuyo orìgen no puede determinar,quiza sea imputable a duna reacciòn local frente a agresiones por partìculas que existen en el ambiente (polvo, etc.)