| Quercetin has proven to possess a wide range of pharmacological properties such as anti-cancer activity, antioxidation, cardiovascular protective effects, as well as others several physiological functions and pharmacological effects. However, the structure of quercetin contains some hydroxyl groups with both weak lipophilicity and poor hydrophilicity due to the formation of hydrogen bonds between molecules with high lattice energy. In vivo, due to its strong first pass effect, the quercetin can be rapidly absorbed and metabolized. The bioavailability is too low to be widely used as a pharmaceutical in clinical trials. Therefore, the aim of this essay tries to improve its bioavailability and enhance its activities by modifying qurecetin.To improve the solubility, and lower the first pass effect of qucercetin, three esterified derivatives of quercetin were synthesized using ethyl bromoacetate, ethyl chloroacetate and qucercetin as substrates. Further, carboxyl derivatives of quercetin were also synthesized.The DMF was used as solution, K2CO3as acid-binding agent, and stirred2h under30℃, the product was Eaql. The other reatcion which used NaHCO3as acid-binding agent, stirred3h under40℃, the products were Eaq3and Eaq4. In addition, Eaq1,3,4were used as the raw materials for the next reaction.The reaction condition were optimized, and the structures of each compound was characterized by IR, MS,13C NMR spectra.The indicators related to oxidative stress were determined using commercially available assay kits. T3-(4,5-dimethylthiazal-z-yl)-2,5-diphenylterazolium (MTT) assay was used to assess the survival rate of HUVECs under different concentrations of each derivative. Cells were divided into four experimental groups:control, positive control, H2O2, experiment. The LDH release rate, SOD activity, NO production, MAD content was measured in different groups. The absorption of qucercetin and its derivatives in HUVECs was identified using high-performance liquid chromatography (HPLC). Results were as follows:1. The oxidative injury model was established with H2O2(100μmol/L). Morphological characteristics of endothelial cell apoptosis were observed by confocal laser scanning microscopy (CLSM). The morphological changes associated with apoptosis could be observed in oxidative injured endothelial cells, which contained cell shrinkage, retraction from neighboring cells and irregular nuclei, chromatin condensation.2. The effect of qucercetin and derivatives on the viability of normal HUVECs was dose-dependent. When the concentration of qucercetin and its derivatives were more than150μmol/L, the survival rate are significantly less than that in the control group (p<0.05).3. To investigate the protective effect of qucercetin and its derivatives on endothelial cell against H2O2-induced oxidative damage, the indicators of oxidative stress-related cell injury (LDH, MDA, NO, SOD) were measured in the present study. The results show that there was quite a few differences between qucercetin and its dervatives in terms of protection of HUVECs. The Eaq dervatives was higher than qucercetin. Nonetheless, when HUVECs were pre-incubated with qucercetin and its derivatives, these H2O2-induced cellular events were largely attenuated, and endogenous antioxidant preservation was enhanced.4. The absorption of qucercetin and different derivatives in HUVECs was reflected by the concentration of extracellular. The results showed that the concentration of the extracellular qucercetin was related to the incubation time (0-12h). The concentration of the extracellular Eaq derivatives was higher than qucercetin in the same incubation time, while, the Aq dervatives was a little low than qucercetin. |
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