Research advances of phosphokinases for α-synuclein / 中国药理学与毒理学杂志

Abnormal aggregation of α-synuclein(α-Syn) is thought to be a key event in the pathogenesis of Parkinson disease (PD). In recent years, it was shown that above 90% of α-Syn deposited in Lewy bodies in brain tissues from patients with PD is phosphorylated, which suggested that α-Syn phosphorylation be connected with the occurrence of PD. Several kinds of phosphokinases can make α-Syn phosphorylated, however the precise roles of these phosphokinases in PD are less clear.

The effects of flavonoids extracts from semen Astragali complanali on the growth of liver cancer and immune function / 肿瘤

Objective:To study the effect of flavonoids extracts from semen Astragali complanati (FAC) on the growth of hepatocellular H22 cells and elucidate its action mechanism. Methods:The mouse model bearing H22 tumor cells was established. The effects of FAC on the growth of xenografted H22 tumor, the immune organ, survival time, phagocytic function of macrophages, and lymphocyte transformation in tumor-bearing mice were observed. Results:The growth of H22 transplanted tumor was significantly inhibited by FAC at high, middle and low doses,compared with normal control group (P0.05). FAC markedly elongated the survival time of tumor-bearing mice. The high, middle and low doses of FAC elongated the survival time of tumor-bearing mice by 64.9%, 56.7% and 28.1%, which were significantly different with control group (P<0.01). The high, middle and low doses of FAC greatly increased the thymus index and spleen index of tumor-bearing mice (P<0.05, vs control) and elevated the phagocytic function of macrophages and lymphocyte transformation capability (P<0.01, vs control). The effect of CTX on immune function of tumor-bearing mice was opposite with FAC. The difference between CTX group and control group was significant (P<0.01). Conclusion: FAC inhibits the growth of H22 hepatoma, elongates the survival time, and elevates the non-specific immune function of tumor-bearing mice, indicating that FAC maybe exert its anti-tumor effect via regulating immune function of tumor-bearing mice.

A Study of the mechanism and inhibitory effect of aspirin on U251 cells in vitro / 中国药理学通报

Aim To study the mechanism and inhibitory effect of aspirin on U251 cells in vitro.Methods The effects of aspirin on proliferation of U251 cells were assessed using the MTT assay.Cell cycle analysis was done by flow cytometry.AnnexinⅤ-FITC Apoptosis Detection Kit was used to detect apoptosis of cells.Western blot was employed to analyze expression of apoptosis-related protein Bcl-2 and Caspase-3.Results The growth inhibiton of U251 cells by aspirin was in a time-and-dose-dependent manner.After treatment with 8 mmol?L-1,cell cycle was arrested at G2/M phase.Aspirin also significantly enhanced apoptosis of U251 cells with down-regulated anti-apoptotic protein Bcl-2,and activation of Caspase-3.Conclusions Aspirin can significantly inhibit the growth of U251 cells through inducing cell apoptosis in vitro.

Curcumin inhibits the adherence of leukocytes to BMECs induced by TNF-? in vitro / 中国药理学通报

Aim To investigate the effects of curcumin on the adherence between isolated rat brain microvascular endothelial cells(BMECs)and leukocytes induced by TNF-? in vitro.Methods The adherence ofleukocytes to BMECs and the effects of curcumin were determined by myeloperoxidase.The expression of ICAM-1 was detected by RT-PCR and immunoblotting.Results Curcumin inhibited the TNF-? stimulated adherence of leukocytes to BMECs.Pretreament of curcumin also inhibited TNF-?-induced increases in the mRNA and protein levels of ICAM-1 in BMECs.Conclusions Curcumin could protect the endothelial cells against damage caused by TNF-?.The protective effects of curcumin may be mediated through downregulation of the expression of ICAM-1.

Effect of aspirin on learning and memory in Alzheimers disease rats and its molecular mechanism / 中国药理学通报

AIM To observe the effect of aspirin on a model of Alzheimers disease in rats and its molecular mechanism. METHODS The AD pathological model was made by hippocampal CA 1 lesions with stereotaxic mini-injection of quinolinic acid;the rats learning and memory was observed by Y-maze; the apoptosis of hippocampal cells were detected by using flow cytometry and electronic microscope; the content of calcium in AD rats hippocampus was determined by atomic absortion spectrophotometer. RESULTS Aspirin was shown to improve learning and memory deficiency in rats with bilateral hippocampal lesions induced by quinolinc acid, to decrease apoptosis rate in hippocampal cells significantly and to reduce the concentration of calcium in hippocampus. CONCLUSION The protective effects of aspirin on a model of AD in rats may be involved in antagonism of calcium and inhibition of apoptosis in hippocampal cells induced by quinolinic acid.

Neuroprotective Actions and Possible Underlying Molecular Mechanisms of Valproate / 中国药理学通报

Valproate (VPA) has long been used for the treatment of bipolar mood disorder. VPA is effective in control of mania and depression. Recent studies have demonstrated that VPA has profound neuroprotective effects in against various apoptotic stimuli. Moreover, VPA can promote neurogenesis, neuronal proliferation and differentiation. Although intensive research has been dedicated to VPA′s neuroprotection, the molecular mechanisms by which VPA protects neurons are still not fully understood. In this paper, recent progresses in the study of VPA′s neuroprotection and underlying mechanism are reviewed.

Study on antiangiogenesis effects of quercetin / 中国药理学通报

Aim To study the effects of Quercetin on the angioge ne sis and cultured human vascular endothelial cells (HUVEC).Methods In vivo, the effects of Quercetin on angiogenesis induced by vascular en dothelial growth factor (VEGF) and basic fibroblast growth factor(bFGF), were observ ed by chorioallantioic membrane (CAM) test. The effects of quercetin on proliferation of human vascular endothelial cells (HUVEC) were assessed by MTT assay. The effects of Quercetin on cell cycle of HUCEC were observed by flow cytometer (FCM ).Results The angiogenesis induced by VEGF in CAM was strongly inhibited by Quercetin with 0.1, 0.05 and 0.025 mmol?L -1; The angiogen esis induced by bFGF in CAM. was strongly inhibited by Quercetin with 0.1 and 0 .05 mmol?L -1. Quercetin markedly inhibited the proliferation of HUVEC with 240,120,60 and 30 ?mol?L -1. The inhibition rate was 67.0%,58.1% ,39.7% and 20.7% respectively. Quercetin at the concentration of 240 ?mol? L -1 and 120 ?mol?L -1 resulted in S,G 2 arrest of HUVEC. Conclusion Quercetin has substantial inhibitory effects on angiogenesi s induced by VEGF and bFGF, and on proliferation of HUVEC.

The role of autophagy in cell survival and tumor development / 中国药理学通报

Autophagy occurs in all types of eukaryotic cells, which has a rigid connection with the normal or abnormal development of cells and is associated with many diseases. There're lots of molecular control elements and multiple signaling pathways involved in regulating autophagy. As a form of type Ⅱ programmed cell death, autophagy participates in maintaining cell homeostasis and pathogenesis of various of diseases through interacting with apoptotic pathway. Recent studies show that autophagy has effects on the occurrence and development of tumor cells through influencing on cell cycle, apoptosis-associated factors and angiogenesis.

The research progress of cobra venom secretory phospholipase A_2 / 中国药理学通报

Cobra venom secretory phospholipase A_2 (sPLA_2) is an important component of cobra venom which has a variety of biological activities. Recent studies are mainly focusing on each pharmacological active component of venom, SPLA_2 is one of them. This review summarized the structure, purification and biological activities of cobra venom sPLA_2 with emphasizing its diverse pharmacological effects and toxicity. In addition, some mechanisms of actions of sPLA_2 and possible applications of sPLA_2 were also discussed.

Primary studies on the anti-uterine cervix cancer effects of the extract ZE4 from Lysmachia clethroides Duby / 中国药理学通报

Aim To estimate the anti-uterine cervix cancer effects of the extracts from Lysimachia clethroides Duby in vivo and in vitro. Methods Inhibitory effect on growth was observed by MTT, 3H-TdR and colony-forming units assay. Apoptosis was detected by Hoechst fluorescent staining analysis. The effect on cell migration and morphology was observed by scratch test; Detecting effects of ZE4 on transplant tumor (U14) in mice through observing the tumor weight and organ index. Results ZE4 could inhibit the growth and migration of HeLa cell significantly and induce cell apoptosis. Its half inhibitory concentration (IC50) at 48h was 40.56 mg?L-1 by 3H-TdR assay. The inhibition rate of ZE4 against U14 was 49.9% at the dose of 400 mg?kg-1. Conclusions ZE4 could inhibit the growth of uterine cervix cancer in vitro and in vivo.

Regulation Effect of Water-extraction from Ganoderma Lucidum (Lyess.ex Fr) karst. on Human Immune cells and IL-6 / 中成药

Objective:To study the regulation effect of water extraction from Ganoderma Lucidum (Lyess. ex Fr) karst (GL W) on human immune cells and cytokine. Methods: With the technologies of MTT and FACS, the proliferation of T lymphocyte subgroup and IL 6 production in human peripheral blood lymphocytes (PBL) were studied. Results: 1. In the absence of mitogin, GL W could induce not only the inactive lymphocyte but also the PHA activited lymphocyte to proliferate in the similar concentration. The proliferation in the later was more obvious ( P

Induction of apoptosis and inhibition of telomerase activity by extract of Fagopynum cymosum(Fr4) in human leukemia HL-60 cells / 中国药理学通报

Aim To study effect of the extract of Fagopynum cymosum(Fr4) on the apoptosis and telomeraseactivity in human leukemia HL-60 cells.Methods HL-60 cells were treated with Fr4 and inhibition of proliferation was measured with MTT assay.Cell morphology before and after the treatment was examined with light and electron microscopy.FILC-Annexin-V and PI double staining was used to detect cell membrane-mediated apoptosis by FCM.DNA fragmentations were analyzed with DNA gel electrophoresis.Furthermore,telomerase activity was determined with PCR-ELISA-based telomeric repeat amplification(TRAP).Results The proliferation of HL-60 cells was inhibited by Fr4 with an IC_(50) of 115 mg?L~(-1).Typical morphology and biochemical feature of apoptosis was observed with Fr4 60～240 mg?L~(-1).The percentages of early apoptosis cells were increased in a dose-dependent manner.Telomerase activity was decreased in a dose-dependent manner during the process of apoptosis.Conclusion Fr4 induced apoptosis in HL-60 cells.Down-regulation of the telomerase activity in HL-60 cells might be contributed to Fr4-induced apoptosis.

Mechanisms of curcumin protecting endothelial cells against ischemia and reperfusion injury / 中国药理学通报

Aim To investigate the mechanisms in protecting HUVEC against ischemia/reperfusion(I/R) injury directed by curcumin.Methods Hypoxia/reoxgenation(H/R) model was established on HUVEC.MTT colorimetric assay was used to observe the injury degree of hypoxia and reoxygenation at the different time.With preconditioning by different concentration of Cur,the survival rate of HUVEC subjected to H/R was assessed by MTT colorimetric assay.Pretreated with Cur(5 ?mol?L-1),the expression of LC3,cathepsin B,cathepsin L,Bax and Bcl-2 were observed by fluorescent staining and Western blot in HUVEC during H/R process.Results Cur(1.25~5 ?mol?L-1) played a protective role during H/R in HUVEC in a dose-dependent manner.During H/R,the expressions of LC3,cathepsin B and the ratio of Bax/Bcl-2 increased,and the nuclear translocation of cathepsin L was induced;when cur was pretreated,LC3 was furtherstrengthened,at the same time,the up-regulation of cathepsin B,the ratio of Bax/Bcl-2 and the nuclei-location of cathepsin L were inhibited partly by Cur.Conclusions Cur can raise the survival rate of HUVEC in the process of H/R.Cur increases the autophagy activity,depresses cathepsins and Bax/Bcl-2 to protect the endothelial cells.

Inhibition Effect of Xinnaotong on Endothelial Cells and Platelets Expression Adhesion Molecule in Vitro / 中成药

Objective:To study the action of Xinnaotong on adhesion molecule expression by cultured endothelial cells and platelets. Methods: Tumor necrosis factor ?(TNF ?) stimulated ICAM I expression on the cell surface was studied with human umbilical vein endothelial cells(HUVEC).Thrombin stimulated expression of platelet P selectin was studied with human blood platelets. Adhesion molecule expression was measured by flow cytometry. Results: ICAM I molecule expression on HUVEC was significantly stimulated by TNF ?. The stimulatory effect of TNF ? on HUVEC was inhibited by Xinnaotong(0.25～2g/L) in a concentration dependent manner. The same dose of Xinnaotong can inhibit the p selectin expression on human blood platelets stimulated by thrombin. Conclusion: Xinnaotong inhibites expression of adhesion molecues(ICAM I, p selectin) in HUVEC and in human blood platelets.