Xiaoyun Lu

Evaluation to the antioxidant activity of total flavonoids extract from persimmon (Diospyros kaki L.) leaves

Persimmon leaves are commonly consumed as beverages, but are also used as a popular folk medicine in China. The purpose of this work is to assess the antioxidant activity of an extract of total flavonoids from persimmon leaves (TFPL). The effect of TFPL on total antioxidant activity, reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH()) radical scavenging, superoxide anion (()O(2)(-)) radical scavenging, hydroxyl (OH()) radical scavenging and metal chelating activities was examined. We found that TFPL possesses considerable amounts of flavonoids (192μg catechin equivalent/g of extract). The effect of this extract in total antioxidant activity, scavenging activity of superoxide anion and hydroxyl radical, reducing power and iron chelating activity was significantly better than that of rutin. However, the effect of TFPL in free radical scavenging of DPPH() was significantly not as good as than rutin. In addition, TFPL significantly decreased the level of reactive oxygen species (ROS) and malondialdehyde (MDA), while increasing the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in MC3T3-E1 cells in a dose-dependent manner. In conclusion, TFPL possess potent antioxidant and free radical scavenging activities. These antioxidant activities could contribute, at least in part, to the traditionally claimed therapeutic benefits of persimmon leaves.

Essential Role of the p110β Subunit of Phosphoinositide 3-OH Kinase in Male Fertility

In the absence of p110β function, spermatogenesis is dramatically disturbed because of a progressive reduction of differentiating spermatogones. Genetically modified mice and pharmacological inhibition of p110β confirmed this enzyme as the main PI3K isoform activated downstream of c-Kit.

3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer's disease via mitochondria protection mechanism

Alzheimers disease (AD) is induced by many reasons, including decreased cellular utilization of glucose and brain cell mitochondrial damages. Degradation product of microbially synthesized polyhydroxybutyrate (PHB), namely, 3-hydroxybutyrate (3HB), can be an alternative to glucose during sustained hypoglycemia. In this study, the derivative of 3HB, 3-hydroxybutyrate methyl ester (HBME), was used by cells as an alternative to glucose. HBME inhibited cell apoptosis under glucose deprivation, rescued activities of mitochondrial respiratory chain complexes that were impaired in AD patients and decreased the generation of ROS. Meanwhile, HBME stabilized the mitochondrial membrane potential. In vivo studies showed that HBME crossed the blood brain barrier easier compared with charged 3HB, resulting in a better bioavailability. AD mice treated with HBME performed significantly better (p < 0.05) in the Morris water maze compared with other groups, demonstrating that HBME has a positive in vivo pharmaceutical effect to improve the spatial learning and working memory of mice. A reduced amyloid-β deposition in mouse brains after intragastric administration of HBME was also observed. Combined with the in vitro and in vivo results, HBME was proposed to be a drug candidate against AD, its working mechanism appeared to be mediated by various effects of protecting mitochondrial damages.

Sustained release of PI3K inhibitor from PHA nanoparticles and in vitro growth inhibition of cancer cell lines

The phosphoinositide-3-kinases (PI3Ks) are a conserved family of lipid kinases that phosphorylate the 3-hydroxyl group of phosphatidylinositols in response to extracellular stimuli. PI3K pathway is enrolled in different kinds of human cancer and plays a prominent role in cancer cell growth and survival. Several PI3K inhibitors have been recently identified but some PI3K inhibitors with high potency in vitro do not show satisfactory effects in animal cancer models because of the poor pharmaceutical properties in vivo such as poor solubility, instability, and fast plasma clearance rate. In this study, we developed a sustained release system of PI3K inhibitor (TGX221) based on polyhydroxyalkanoate nanoparticles (NP) and used it to block proliferation of cancer cell lines. TGX221 was gradually released from PHA-based NP and growth of cancer cell lines was significantly slower in NP-TGX221-treated cells than in either negative controls or in cells receiving free TGX221. Since poor bioavailability and limited in vivo half-life are common features of hydrophobic PI3K inhibitors, our results open the way to similar formulation of other PI3K blockers and to new strategies in cancer treatment.

Sulphated modification of a polysaccharide obtained from fresh persimmon (Diospyros kaki L.) fruit and antioxidant activities of the sulphated derivatives

Free radicals and other reactive oxygen species (ROS) are believed to play significant roles in ageing as well as in a number of degenerative or pathological diseases. This paper reports the preparation, characterisation and potential antioxidant activity of a type of chemically sulphated polysaccharide isolated from fresh persimmon (Diospyros kaki L.) fruit. Three sulphated derivatives with variable degrees of substitution (0.8, 1.7 and 2.5) were obtained by the chlorosulphonic acid-pyridine method. The sulphated derivatives all showed dose-dependent reducing power and free radical scavenging effect of 1,1-dipheny-l-2-picrylhydrazyl, superoxide anion and hydroxyl. Our results showed that the sulphated modification of polysaccharides significantly increased their antioxidant activities and may be an effective way to prepare these valuable derivatives.

Sulfated modification and immunomodulatory activity of water-soluble polysaccharides derived from fresh Chinese persimmon fruit

In this study, three kinds of chemically sulfated polysaccharides (PFP-S) were derived from a water-soluble polysaccharide of persimmon fruit with chlorosulfonic acid-pyridine method. Relationship between the degree of substitution and immunomodulatory activity of PFP-S was examined with the splenocytes experiment. The results showed that the splenocytes-activating activity was significantly enhanced by PFP-S in all the groups compared with control group (P<0.01). PFP-SII exhibited the most potent splenocytes-activating activity by increased cytokine production and NO release. It also suggested that the sulfate groups and molecular weight of polysaccharides are key factors to regulate the immunomodulatory activities.

Sulfation modification and anticoagulant activity of the polysaccharides obtained from persimmon (Diospyros kaki L.) fruits

The optimal conditions for sulfation of polysaccharides from persimmon fruits (PFP) with chlorosulfonic acid-pyridine (CSA-Pyr) method were determined by response surface methodology. Box-Behnken design was applied to evaluate the effects of three independent variables (volume ratio of Pyr to CSA, volume ratio of PFP to SO(3)Pyr and reaction time) on the degree of substitution (DS), molecular weight (MW) and activated partial thromboplastin time (APTT) of sulfated polysaccharides (PFP-S). The APTT activity of PFP-S could be improved by application of various volume ratio of Pyr to CSA, volume ratio of PFP to SO(3)Pyr and reaction time, which was possible due to the degradation of polysaccharides to different extent and increasing of DS. The optimal conditions to obtain the strongest APTT of PFP-S were the volume ratio of CSA to Pyr of 1:8, the volume ratio of SO(3)Pyr to PFP of 1:3.6 and the reaction time of 3 h, respectively.

Protective effects of sulfated chitooligosaccharides against hydrogen peroxide-induced damage in MIN6 cells.

Sulfated chitooligosaccharides (COS-S) with different degrees of substitution (DS) were obtained by the chlorosulfuric acid/pyridine method. Protective effects of COS-S against hydrogen peroxide (H(2)O(2))-induced damage were investigated in pancreatic β-cells MIN6 cell line. The cell viability, morphology, insulin contents, malondialdehyde (MDA) inhibition, lactate dehydrogenase (LDH) release and the levels of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidise (GPx) were evaluated under oxidative damage by 150 μM H(2)O(2) for 6h. COS-S did not show any harmful or inhibitory effect on cell growth at concentrations ranging from 0.1 to 0.5 mg/ml. While COS-S could enhance the cell viability, decrease the production of ROS, and reduce the MDA level as well as LDH level in oxidative damaged β-cells by being an antioxidant. The underlining mechanisms of protective effects of COS-S are partly due to the enhancement of antioxidant enzyme activity and inhibition of intracellular ROS production, along with suppressing MIN6 cell apoptosis subsequent to the amelioration of ROS. Moreover, increased DS might contribute to the defense mechanisms against H(2)O(2)-induced oxidative damage in MIN6 cells. These results indicated that the antioxidant properties of COS-S hold great potential for the oxidative diseases treatment, and the sulfate content of polysaccharides made great role in regulating antioxidant activities.

Groebke multicomponent reaction and subsequent nucleophilic aromatic substitution for a convenient synthesis of 3,8-diaminoimidazo[1,2-a]pyrazines as potential kinase inhibitors

In a program aimed at discovering novel protein kinase inhibitors, a convenient synthesis of 3,8-diaminoimidazo[1,2-a]pyrazines has been developed exploiting the isocyanide-based multicomponent Blackburn reaction, followed by a nucleophilic aromatic substitution with ammonia or primary and secondary amines. The potential of the reported scaffold is strengthened by the inhibition of STAT5-dependent transcription displayed by four of the synthesized compounds.

Protective effects of sulfated chitooligosaccharides with different degrees of substitution in MIN6 cells.

Chitosan, a naturally occurring biopolymer, has received considerable attention for pharmaceutical applications due to its biocompatible, biodegradable and less toxic properties. In this study, sulfated chitooligosaccharides (COS-S) with different degrees of substitution (DS) were prepared to improve both its water-solubility and bioactivity. Additionally, the protective effects of COS-S on hydrogen peroxide (H(2)O(2))-induced dysfunction in MIN6 cells were investigated. COS-SI (DS, 0.8) and COS-SII (DS, 1.9) significantly increased the cell viability in a dose-dependent manner. COS-S also significantly suppressed NO production, the activity and mRNA expression of iNOS, and the protein level of NF-κB protein p65, which were activated by H(2)O(2). Furthermore, we demonstrated that COS-S led to an increase in the Bcl-2/Bax mRNA expression ratio and the inhibition of Caspase-3 mRNA expression in H(2)O(2)-stimulated MIN6 cells. Additionally, COS-SII (DS, 1.9) exhibited a superior protective effect on H(2)O(2)-induced apoptosis compared to COS-SI (DS, 0.8). These results indicated the good anti-oxidative capacity of COS-S and the possible mechanism via the blockade of the NF-κB signaling pathway. The protective effects of COS-S against oxidative injuries in MIN6 cells were depended on both DS and concentration.