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1.
J Enzyme Inhib Med Chem ; 36(1): 2104-2117, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34579614

RESUMO

Tyrosinase (TYR) inhibitors are in great demand in the food, cosmetic and medical industrials due to their important roles. Therefore, the discovery of high-quality TYR inhibitors is always pursued. Natural products as one of the most important sources of bioactive compounds discovery have been increasingly used for TYR inhibitors screening. However, due to their complex compositions, it is still a great challenge to rapid screening and identification of biologically active components from them. In recent years, with the help of separation technologies and the affinity and intrinsic activity of target enzymes, two advanced approaches including affinity screening and inhibition profiling showed great promises for a successful screening of bioactive compounds from natural sources. This review summarises the recent progress of separation-based methods for TYR inhibitors screening, with an emphasis on the principle, application, advantage, and drawback of each method along with perspectives in the future development of these screening techniques and screened hit compounds.


Assuntos
Produtos Biológicos/farmacologia , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Ultrafiltração
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(6): 1715-1723, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36476894

RESUMO

OBJECTIVE: To explore the roles and relative mechanism of resveratrol against T-ALL through detecting the signaling molecules in IL-7 and JAK/STAT pathway. METHODS: In vitro experiments, Molt4 cells were divided into 3 groups, including the control group, the DMSO group and resveratrol-treated group (Res group). The control group cells without any treatment, the DMSO group cells treated with 0.05% DMSO for 48 hours, the Res group cells treated with 200 µmol/L resveratrol for 48 hours. In vivo experiments, female C57BL/6J mice (6-8 weeks) were randomly divided into the control group, the T-ALL model group (T-ALL group), and Res treatment group (Res group). The control group mice treated with 0.05% DMSO by intragastric treatment, the T-ALL group mice treated with 0.05% DMSO by intragastric treatment, and the Res group mice treated with 10 mg/ml resveratrol. Expression of IL-7, IL-7R and Pim1 mRNA in the cells and mice spleen tissues were detected by RT-qPCR. Cell proliferation ability was detected by CCK-8. The expression of JAK1, JAK3, STAT5, phosphorylated JAK1 (p-JAK1), phosphorylated JAK3 (p-JAK3), phosphorylated STAT5 (p-STAT5) and Pim1 were detected by Western blot. ELISA was used to detect the IL-7 and IL-7R in the cells and mice serum of each groups. RESULTS: Resveratrol could inhibit the proliferation ability of Molt4 cells, decrease the relative levels of p-JAK1, p-JAK3, p-STAT5, Pim1 protein, and the expression levels of Pim1, IL-7 and IL-7R mRNA in cells and mice spleens, reduce the IL-7 and IL-7R in Molt4 cells and mice serum. CONCLUSION: Resveratrol may inhibite IL-7-medicated JAK/STAT signaling pathway to reduce the expression of target protein Pim1 to further exert its anti-T-ALL effects.


Assuntos
Leucemia , Transdução de Sinais , Feminino , Camundongos , Animais , Camundongos Endogâmicos C57BL , Resveratrol , Interleucina-7 , Janus Quinases , Fatores de Transcrição STAT , RNA Mensageiro , Linfócitos T
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