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Pak J Pharm Sci ; 32(6): 2565-2572, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31969287


Some patients experience lesser degrees of platelet inhibition, which is known as clopidogrel resistance (CR). The goal of our study was to investigate the effects of Xuefu Zhuyu decoction on CR in coronary artery disease patients and whether P2Y12 polymorphisms and its methylation were related to drug response or not. 49 patients diagnosed with CR were randomly divided into control and treatment groups. Platelet functions were measured using Verify-Now P2Y12 assay. By restriction fragment length polymorphism-polymerase chain reaction, the single-nucleotide polymorphisms of rs2046934 and rs6785930 were genotyped. Using bisulphite pyrosequencing assay, we investigated the association of the P2Y12 gene DNA methylation levels and the effects of Xuefu Zhuyu decoction on CR. The results showed that the decoction improved CR (P=0.005), and the patients with the TT genotype in rs2046934 received substantial benefits from Xuefu Zhuyu Decoction, in both P2Y12 reaction units (PRU) and inhibition percentage (PPRU= 0.016; Pinhibition percentage = 0.028). And patients with lower methylation levels of CpG1 were more likely to be TT carriers in rs2046934 (CpG1TT Vs. CpG1TC+CC (%): 39.47±6.20 vs.45.70±8.47, P=0.044). In conclusion, our study indicated that Xuefu Zhuyu decoction might be useful for overcoming CR and the polymorphism of rs2046934 might influence the drug effect.

Exp Ther Med ; 14(2): 1653-1658, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28810632


An anticancer compound, triterpene glycoside, was isolated from Holothuria nobilis Selenka. Its chemical structure and configuration were determined by two-dimensional nuclear magnetic resonance spectroscopy and electrospray ionization mass spectrometry. The novel active compound was identified as nobiliside D, with the molecular formula C40H61O17SNa and chemical name 3-O-[-ß-D-pyranosyl (1-2)-4'-O-sulfon-ate-ß-D-xylopyranosyl]-alkoxy-9-ene-3ß, 12α, 17α, 25ß-4 alcohol. An antitumor test was performed using xCELLigence Real-Time Cell Analysis. Nobiliside D exhibited inhibitory effects on human leukemic cell line K562, human leukemia cell line U937, human lung cancer cell line A-549, human cervix carcinoma cell line HeLa, human breast cancer cell line MCF-7 and human liver carcinoma cell line HepG2. Nobiliside exhibited the greatest inhibitory effect on K562 and MCF-7 cells with an IC50 of 0.83±0.14 and 0.82±0.11 µg/ml, respectively. When human tumor cell lines K562 and MCF-7 were treated by nobiliside D (0.5 µg/ml) for 24 h, 45.8% of K562 cells and 58.7% of MCF-7 cells were apoptotic, whereas only 0.5% of un-treated control cells were apoptotic. These data indicate the compound should offer potential as a novel drug for the treatment of a range of cancers.

Oncotarget ; 8(15): 25552-25563, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28424423


The antidepressant-like effect of trans-astaxanthin, a compound present rich in algae, was evaluated through behavioral and neurochemical methods. Results showed that trans-astaxanthin treatment significantly decreased the immobility time in force swim test and tail suspension test, but did not influence locomotor activity. Trans-astaxanthin treatment did not effectively antagonize hypothermia and ptosis induced by reserpine. However, pre-treatment with para-chlorophenylalanine abolished the anti-immobility effect of trans-astaxanthin in force swim and tail suspension test. These results suggested that the mechanism of antidepressant-like effect of trans-astaxanthin may involve the serotonergic system, but not noradrenaline system. This hypothesis was confirmed by neurochemical assays which showed that trans-astaxanthin increased serotonin levels in the hippocampus, frontal cortex, striatum and hypothalamus. Furthermore, our data suggested that trans-astaxanthin decreased indoleamine 2, 3-dioxygenase activity in the hippocampus, frontal cortex and hypothalamus. Inhibition of indoleamine 2,3-dioxygenase activity subsequently decreased the kynurenine/tryptophan ratio and increased the serotonin/tryptophan ratio in these brain regions. Taken together, these findings indicate that the antidepressant-like effect of trans-astaxanthin involves the serotonergic system.

Antidepressivos/farmacologia , Atividade Motora/efeitos dos fármacos , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/metabolismo , Serotonina/metabolismo , Animais , Comportamento Animal , Monoaminas Biogênicas/metabolismo , Encéfalo/metabolismo , Ativação Enzimática/efeitos dos fármacos , Expressão Gênica , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Camundongos , Monoaminoxidase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Triptofano/metabolismo , Xantofilas/farmacologia