SENSORS AND ACTUATORS B-CHEMICAL
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2025
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IF 7.7
Yue-Yang Zhang,Le-Yu Huang,Huiling Wang,Sixuan Meng,Fei Yang,Shi-Yu Liu
Carboxylesterase 2 (CES2), an extensively expressed serine esterase which widely distributed in various organs and tissues, exerts important roles in maintaining normal physiological function while abnormal expression of CES2 was correlated with many metabolic diseases and cancers. Thus, to develop efficient tool for detection of CES2 activity is of great importance in related clinical diagnosis and research of physiological function of CES2. To date, several enzyme-activated fluorescent probes were developed for CES2 sensing. Among which regulation of CES2 in diseases such as diabetics, colitis, cancers and liver injury could be visualized. However, even though CES2 displayed relatively high expression level in kidney, its regulation in pathological process of kidney injury was rarely studied, and thus related preliminary investigation is in urgent demand. Herein, by rational design and construction of an enzyme-activated fluorescent probe (named as DDXB ) with high catalytic efficacy, sensitivity and specificity toward CES2, down-regulation of CES2 activity in acetaminophen (APAP)-induced liver injury and dextran sulfate sodium (DSS)-induced colitis model was successfully visualized. Most importantly, aberrant up-regulation of CES2 in streptozotocin (STZ), renal ischemia reperfusion (IR) injury (RIRI) and cisplatin (CDDP)-induced kidney injury model was first revealed via DDXB- based fluorescence imaging and further confirmed by immunohistochemistry (IHC) staining. Thus, preliminary evidence for identifying CES2 as potential biomarker of kidney injury were first provided, and the newly developed probe could serve as an efficient tool for related diagnosis or further investigation of CES2 physiological function in more diseases.
研究领域:
生物化学
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医学诊断
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病理学
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产品关联
DOI
高影响因子
Chinese Journal of Natural Medicines
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2013
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IF 0
Xue-Jian LI,Zheng-Cai DU,Yan HUANG,Bu-Ming LIU,Wen-Ji HU,Wen-Jie LU,Jia-Gang DENG
Aim To synthesize three novel esterified-derivatives of mangiferin and evaluate their hypoglycemic activities. Methods Acetic, propionic, and butyric anhydride were reacted with mangiferin, respectively. The hypoglycemic activity of the derivatives was evaluated using a hyperglycemic mouse model induced by streptozotocin (STZ), and the islet cells were checked by biopsy inspection. Results 7, 2′, 3′, 4′, 6′-penta-acetyl-mangiferin (PAM), 3, 6, 7, 2′, 3′, 4′, 6′-hepta-propionyl-mangiferin (HPM) and 3, 6, 7, 2′, 3′, 4′-hexa-butyryl-mangiferin (HBM) were synthesized and their structures were identified by MS, 1 H, 13 C NMR, and 2D NMR. These three compounds were reported for the first time. PAM group (0.5, 0.25 mmol·kg −1 ), HPM group (0.5, 0.25 mmol·kg −1 ), and HBM group (0.5, 0.25, 0.125 mmol·kg −1 ) mice showed strong hypoglycemic activity ( P < 0.01); mangiferin group (1, 0.5 mmol·kg −1 ), PAM group (0.125 mmol·kg −1 ) and HPM group (0.125 mmol·kg −1 ) showed marginal hypoglycemic activity ( P < 0.05); mangiferin group (0.25 mmol·kg −1 ) had the potential for a hypoglycemic effect, although it did not demonstrate that statistically. In histological examination, the islet cells of the PAM, HPM, and HBM groups could recover from the STZ damage; islet cells of the mangiferin group could recover also, but less than the esterified-derivative groups. Conclusion Derivatives could repair the damaged islet cells, and had higher lipid-solubility and stronger hypoglycemic activity than mangiferin itself. There existed a structure activity effect, and a solubility effect relationship: the larger esterification moieties, or the higher lipid-solubility, the stronger the hypoglycemic activity (no ester → acetyl → propionyl → butyryl). Esterified derivatives of mangiferin are potential compounds for new anti-diabetes drugs.
研究领域:
药理学
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有机化学
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糖尿病研究
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DOI
危险品化学品经营许可证（带存储）