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Neurosci Lett ; 641: 1-7, 2017 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-28122257


Glucagon-like peptide 1 receptor (GLP-1R) agonists administered before or immediately after induction of experimental stroke have been shown to provide acute neuroprotection. Here, we determined whether delayed treatment with a GLP-1R agonist could improve metabolic and functional recovery after stroke. Rats were subjected to middle cerebral artery occlusion (MCAO) and given the well-established GLP-1R agonist liraglutide (50, 100, or 200µg/kg) or normal saline (NS) daily for 4 weeks, starting 1 day after MCAO. Cerebral glucose metabolism and neurological deficits were evaluated using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging and modified neurological severity score (mNSS) test. Levels of neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), von Willebrand factor (vWF), and GLP-1R were assessed by immunohistochemical staining and Western blot analysis. PET imaging showed that animals treated with liraglutide had significantly higher 18F-FDG accumulation in the cerebral infarction compared with animals treated with NS. Liraglutide significantly reduced the mNSS score. It also greatly increased the expression of NeuN, GFAP, vWF, and GLP-1R in the cerebral ischemic area at postoperative week 4. These results demonstrated metabolic and functional recovery after delayed treatment with liraglutide in a rat model of cerebral ischemia.

Isquemia Encefálica/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Liraglutida/uso terapêutico , Trifosfato de Adenosina/metabolismo , Animais , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Ingestão de Alimentos/efeitos dos fármacos , Metabolismo Energético , Masculino , Proteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Neuropeptídeo Y/metabolismo
Biomed Rep ; 4(2): 173-177, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26893833


Minocycline has been reported to exhibit advantageous effects on ischemic stroke; however, the precise mechanism of minocycline remains to be established. In the present study, human umbilical vein endothelial cells (HUVECs) were subjected to in vitro simulated ischemia/reperfusion conditions to determine the potential effect of minocycline-induced autophagy on HUVEC damage under oxygen-glucose deprivation/reperfusion (OGD/R). The study demonstrated that minocycline enhanced autophagy in a dose-dependent manner in HUVECs exposed to OGD/R, and only low-dose minocycline protected HUVECs from OGD/R-induced damage. Subsequently, 3-methyladenine (3-MA) was added into the culture media and the protective effect of minocycline was abolished. At the same time, it has been observed that simultaneous treatment with 3-MA also inhibited the autophagy activity induced by minocycline. This finding could suggest that autophagy induced by minocycline serves as one of the potential protective mechanism underlying the beneficial effects of minocycline on ischemic injury.

Phytomedicine ; 22(4): 510-5, 2015 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-25925974


OBJECTIVE: The leaves and bark of Metasequoia glyptostroboides are used as anti-microbic, analgesic and anti-inflammatory drug for dermatic diseases in Chinese folk medicine. However, the pharmacological effects and material basis responsible for the therapeutic use of this herb have not yet been well studied. The objectives of this study were to evaluate the anti-inflammatory effects of the proanthocyanidin fraction from the bark of M. glyptostroboides (MGEB) and to elucidate its immunological mechanisms. MATERIALS AND METHODS: The anti-inflammatory activity of MGEB was evaluated using 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in mice. Its potential mechanisms were further investigated by determining its effects on Con A-induced T cell activation and Th1/Th17 responses in vitro. RESULTS: Both intraperitoneal injection and oral administration of MGEB significantly reduced the ear swelling in DNFB-induced ACD mice. MGEB inhibited Con A-induced proliferation and the expression levels of cell surface molecules CD69 and CD25 of T cells in vitro. MGEB also significantly decreased the production of Th1/Th17 specific cytokines (IL-2, IFN-γ and IL-17) and down-regulated their mRNA expression levels in activated T-cells. CONCLUSIONS: MGEB could ameliorate ACD, at least in part, through directly inhibiting T cells activation and Th1/Th17 responses.

Anti-Inflamatórios/farmacologia , Cupressaceae/química , Dermatite Alérgica de Contato/tratamento farmacológico , Ativação Linfocitária/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Citocinas/imunologia , Feminino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Casca de Planta/química , Células Th1/imunologia , Células Th17/imunologia
Zhongguo Zhong Yao Za Zhi ; 38(3): 386-90, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23668015


OBJECTIVE: To study the therapeutic effect of Dabuyin Wan on true precocious puberty of female rats and its possible mechanism. METHOD: Twenty-two-day-old female SD rats were subcutaneously injected with 40 mg x kg(-1) N-methyl-DL-aspartic acid (NMA) at 14:00 and 16:00 every day; meanwhile, the rats were given Dabuyin Wan for intervention. Visual inspection was conducted for the time of vaginal opening. The first estrus was observed by yaginal smear test. Their ovaries and uterus were weighed to calculate organ coefficients. Conventional pathological slices were made to observe morphological changes in ovaries and uterus and calculate the thickness of uterine walls and the number of corpus luteums. The level of E2 in serum was detected to assess the therapeutic effect of Dabuyin Wan on NMA precocious puberty in rats. expressions of GnRH, GPR54 and Kiss-1 mRNA in hypothalamus were measured by semi-quantitative RT-PCR to investigate the possible mechanism of Dabuyin Wan. RESULT: Dabuyin Wan at 3.24 g x kg(-1) and 1.62 g x kg(-1) significantly decreased the organ coefficients in rats with precocious puberty (P < 0.05), decrease the number of vaginal openings in rats (P < 0.01) and the thickness of uterine walls and the number of corpus luteums (P < 0.05), and notably down-regulated expressions of GnRH, GPR54 and Kiss-1 mRNA in hypothalamus (P < 0.05), without significant impact on E2 in serum. CONCLUSION: Dabuyin Wan may inhibit GnRH synthesis and release as well as startup of hypothalamic-pituitary-gonadal axis by down-regulating Kiss-1/GPR54 mRNA expression in hypothalamus, in order to realize the therapeutic effect on true precocious puberty.

Medicamentos de Ervas Chinesas/farmacologia , Ovário/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Estro/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/genética , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Kisspeptinas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas-G/genética , Receptores de Kisspeptina-1 , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Maturidade Sexual/genética , Fatores de Tempo , Vagina/efeitos dos fármacos