Pharmacological activities of myricetin and its glycosides / 中国中药杂志

Myricetin and its glycosides are important flavonols commonly found in plants, and they are natural organic compounds with diverse pharmacological activities. Numerous studies have demonstrated that myricetin and its glycosides are strong antioxidants that have great potential in preventing, alleviating and assisting the treatment of chronic non-infectious diseases such as cancer, diabetes, and cardiovascular diseases. In addition, myricetin and its glycosides also have antiviral, antibacterial, anti-inflammatory, analgesic, liver protection and other pharmacological activities. Myricetin contains more hydroxyl groups in the parent ring structure than other flavonoids, so myricetin and its glycosides have stronger pharmacological activities than other flavonols or flavonoids such as quercetin and kaempferol. Therefore, myricetin and its glycosides have great development and application prospects. In this paper, the classification and distribution of myricetin and its glycosides, their pharmacological activity and mechanism, as well as comparison with other flavonoids were reviewed. In addition, limitations of the current research and application of myricetin and its glycosides were analyzed, and the further studies on pharmacological activities as well as their dose-activity relationship, structure-activity relationship, chemical modification, biosynthesis and application prospects of myricetin and its glycosides were discussed and proposed.

Predicting pharmacokinetics of anti-cancer drug, famitinib in human using physiologically based pharmacokinetic model / 药学学报

This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models. According to published paper, previous studies and the chemical properties of famitinib predicted by ACD/ADME suite and SimCYP, the PBPK models of rat and monkey were established and optimized using GastroPlus. And then, the PBPK models were applied to predict the pharmacokinetic and tissue distribution of famitinib in human. The results showed that the PBPK models of rat and monkey can fit the observed data well, and the AUC0-∞, ratios of observed and calculated data in rat and monkey were 1.00 and 0.97, respectively. The AUC0-∞, ratios of observed and predicted data in human were 1.63 (rat to human) and 1.57 (monkey to human), respectively. The rat and monkey PBPK models of famitinib were well established, and the PBPK models were applied in predicting pharmacokinetic of famitinib in human successfully. Hence, the PBPK model of famitinib in human could be applied in future drug-drug interaction study.

Effect of ginseng total saponins on neuronal apoptosis in rats with traumatic brain injury / 中华神经医学杂志

Objective To observe the effect of ginseng total saponins (GTS) on neuronal apoptosis in rats with traumatic brain injury (TBI), and explore the underlying mechanisms of GTS in the treatment of secondary brain injury. Methods SD rats were randomly divided into sham-operated group, TBI group and GTS-treatment group (n=18). TBI models were established with the modified Feeney's method. Three h after the success of model making, 20 mg/kg GTS was given to the GTS-treatment group through intraperitoneal injection and the same amount of normal saline was given to the TBI group. Twenty-four hours after the success of model making, the rats were sacrificed; the brain water content was measured by wet-dry weight method; the morphological changes of neurons in the hippocampal area were observed under optical microscope after Nissl staining. The neuronal apoptosis and the protein expressions of bax, bcl-2 and caspase-3 in the cortex and hippocampus were determined by TUNEL and immunohistochemical technique, respectively. Results Compared with TBI group,treatment with GTS decreased the water content of the brain, alleviated the damage of hippocampal area,reduced the number of TUNEL positive cells and the bax and caspase-3 positive cells, and increased the number of bcl-2 positive cells. Conclusion GTS can exert a neuroprotective effect in rats with TBI.The underlying mechanism of this effect is potentially related to the elevation of expression of bcl-2 and reduction of expression ofbax and caspase-3, and thereby, restraining the neuronal apoptosis in the brain tissue.

Simultaneous determination of the inhibitory potency of compounds on the activity of five cytochrome P-450 enzymes using a cocktail probe substrates method / 药学学报

This study developed a method for simultaneously assessing the inhibitory potency of compounds on five major cytochrome P-450 ( CYP450) enzymes using a cocktail of probe substrates. A cocktail selective substrates consisting of the phenacetin (PN, CYP1A2), dextromethorphan (DM, CYP2D6), tolbutamide (TB, CYP2C9), omeprazole (OPZ, CYP2C19) and midazolam (MPZ, CYP3A4) was incubated with human liver microsomes. The concentrations of the substrate metabolites paracetamol, dextrorphan, 4-hydroxytolbutamide, 5-hydroxyomeprazole and 1'-hydroxymidazolam were determined by LC/MS/MS in a single assay sample. The method was validated by incubating known CYP inhibitors--alpha-naphthoflavone (ANF, CYP1A2), quinidine (QND, CYP2D6), sulfaphenazole (SUL, CYP2C9), fluconazole (FLU, CYP2C19) and ketoconazole (KET, CYP3A4) with the individual substrates and with the substrate cocktail. The IC50 values were then determined. The IC50s (micromol x L(-1)) were in good agreement with those obtained with individual substrates (alpha-naphthoflavone, 0.18 vs 0.26; quinidine, 0.058 5 vs 0.058 4; sulfaphenazole, 0.48 vs 0.45; fluconazol, 17.5 vs 11.4; ketoconazole, 0.22 vs 0.24) and with previously reported values in the literature. This cocktail probe substrate method can be utilized for the rapid simultaneous determination of the inhibition potential of compounds on the five CYP450 enzymes.

Dynamic changes of plasma NPY before and after vascular intracavitary therapy in patients with lower extremity ASO / 上海第二医科大学学报

Objective To dynamically observe the concentrations of plasma neuropeptide Y(NPY)in the patients with lower extremity arteriosclerosis obliterans(ASO)before and after vascular interventional therapy.Methods The levels of plasma NPY were detected by radioimmunoassay in 13 patients with lower extremity ASO(ASO group)before vascular intracavitary therapy and immediately,1 d,3 d and 5 d after vascular intracavitary therapy.Meanwhile,15 healthy subjects were served as control group.Besides,the ankle-brachial indexes(ABI)and clinical staging of ASO group were also obtained and compared before and 3 d after vascular intracavitary therapy.Results Compared with control group,the level of NPY in ASO group was much higher before vascular intracavitary therapy[(250.67?88.27)pg/mL vs(168.40?64.64)pg/mL,P