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1.
Brain Res ; 1784: 147845, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35219720

RESUMO

Essential oils (EO) are plant extracts widely used for various pharmacological applications and their antioxidant and anti-inflammatory effects have received a lot of attention because they hold the potential to reduce oxidative stress, and neuroinflammation, alterations involved in the pathophysiology of major depressive disorder. This study examined the benefits of administration of flower EO of the Tagetes minuta (10 and 50 mg/kg, intragastric route) in attenuating behavioral, neurochemical, and neuroendocrine changes in animal models of depressive-like behavior induced by acute restraint stress and lipopolysaccharide (0.83 mg/kg, intraperitoneally). We demonstrated that the treatment of mice with flower EO of the T. minuta reversed the depressive-like behavior induced by stress or inflammatory challenge in mice. This effect is most likely due to the reversal of oxidative stress in the hippocampus of mice, the decrease in plasma corticosterone levels, and restoration of the mRNA levels of brain-derived neurotrophic factor, phosphatidylinositol-3-kinase, protein kinase B, and extracellular signal-regulated kinase 2. As an outcome, flower EO of the T. minuta has promising antidepressant properties and could be considered for new therapeutic strategies for major depressive disorder.


Assuntos
Transtorno Depressivo Maior , Óleos Voláteis , Tagetes , Animais , Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Transtorno Depressivo Maior/metabolismo , Modelos Animais de Doenças , Flores/metabolismo , Hipocampo/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Óleos Voláteis/metabolismo , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tagetes/metabolismo
2.
Vaccine ; 38(51): 8099-8106, 2020 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-33190945

RESUMO

Despite the economic and zoonotic relevance of caseous lymphadenitis, a competent immunoprophylaxis tool is still necessary. Here, we evaluated two putative virulence factors of Corynebacterium pseudotuberculosis, rNanH, and rPknG, as recombinant subunit vaccines in a murine model against the infection by C. pseudotuberculosis. Three groups of ten Balb/c mice each were inoculated with a sterile 0.9% saline solution (G1), rNanH (G2), or rPknG (G3) in formulations containing saponin as an adjuvant. The mice received two vaccine doses intercalated by a 21-day interval and were challenged with 2 × 104 CFU/mL of the C. pseudotuberculosis MIC-6 strain 21 days after the last immunization. The total IgG, IgG1, and IgG2a production levels increased significantly in the experimental groups (G2 and G3) on day 42. The highest levels of IgG2a antibodies in G2 and G3 were observed compared to IgG1 levels. G3 showed a significant (p < 0.05) humoral response through higher production of total IgG at day 42 when compared to G2. A significant increase of mRNA expression levels of interleukin (IL)-17, tumor necrosis factor, and interferon-γ was observed only in G2, while IL-4 was significantly produced only by G3. The levels of IL-10 and IL-12 obtained were not significant in any group. The survival rates after the challenge were 20% for G3 and 60% for G2 (p < 0.05). Our findings suggest that the formulation containing rNanH and saponin (G2) resulted in the best protection against the challenge and was able to elicit a Th1 immune response in mice, and can be considered as a promising antigen in the development of an effective vaccine against caseous lymphadenitis.


Assuntos
Infecções por Corynebacterium , Corynebacterium pseudotuberculosis , Linfadenite , Animais , Vacinas Bacterianas , Infecções por Corynebacterium/prevenção & controle , Corynebacterium pseudotuberculosis/genética , Linfadenite/prevenção & controle , Camundongos , Fatores de Virulência/genética
3.
Bioorg Med Chem Lett ; 30(17): 127365, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738968

RESUMO

The present study aimed to investigate the effect of AZT derivates containing tellurium (Te) on human breast cancer cell lines and the mechanisms underlying cell death. The inhibitory effect of AZT and its derivatives (7m and 7r) was determined by the MTT assay (6.25, 12.5, 25, 50 and 100 µM in 24 and 48 h time points), meanwhile the induction of apoptosis and the cell cycle phases was investigated by flow cytometry. The MTT assay showed that AZT derivatives decreased the rate of cell proliferation at concentrations of 12.5 µM, while commercial AZT showed low antitumor potential. In flow cytometric analysis, we demonstrate that the AZT derivatives do not induce apoptosis at the concentration tested and promote the cell cycle arrest in the S phase. Besides, predicted absorption, distribution, metabolization, excretion and toxicity analysis suggest that the compounds possess a good pharmacokinetic profile and possibly less toxicity when compared to conventional AZT. These compounds containing tellurium in their formulation are potential therapeutic agents for breast cancer.


Assuntos
Antineoplásicos/síntese química , Zidovudina/análogos & derivados , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Meia-Vida , Humanos , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos , Telúrio/química , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Zidovudina/síntese química , Zidovudina/farmacocinética , Zidovudina/farmacologia
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