Effects of triterpenic acid from Prunella vulgaris L. on glycemia and pancreas in rat model of streptozotozin diabetes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The effects of triterpenic acid from Prunella vulgaris L. (TAP) on diabetes and its mechanism are uncertain. The aim of this study was to investigate the effects of TAP on antihyperglycemic, antioxidant, and pancreas-protective in streptozotozin (STZ)-diabetic rats.</p><p><b>METHODS</b>The diabetic model was produced by injection of 60 mg/kg STZ. Blood was drawn from the tail vein of rats after 72 hours. Rats with blood glucose ≥ 16.7 mmol/L were considered diabetic. Diabetic rats were randomly divided into four groups: (1) Diabetes rat (STZ), (2) Diabetic rats treated with 50 mg/kg of triterpenic acid from Prunella vulgaris L (STZ + TAP50), (3) Diabetic rats treated with 100 mg/kg TAP (STZ + TAP100), and (4) Diabetic rats treated with 200 mg/kg TAP (STZ + TAP200). Normal rats (n = 10) acted as the control group (NC). TAP was administered by the intragastric route once each day for six weeks. Body weight and the concentration of blood glucose (BG) were measured after three and six weeks. Fructosamine (FMN), malondialdehyde (MDA), and nitric oxide (NO), and the activities of nitric oxide synthase (NOS) and superoxide dismutase (SOD) in serum were determined after six weeks using commercially available kits following the manufacturer's instructions. Pathologic changes in pancreatic β-cells were also investigated by microscopic examination after hematoxylin-eosin (HE) staining. The level of SOD mRNA in pancreatic β-cells was measured by polymerase chain reaction (PCR).</p><p><b>RESULTS</b>The levels of BG, FMN, NO, and MDA and the activities of NOS in serum in the four diabetes groups were significantly increased compared with the control group (P < 0.01). The activity of SOD in serum and the body weight was significantly decreased compared with the control group (P < 0.01). After administration of TAP to diabetic rats for six weeks, the body weight and the levels of BG, FMN, MDA, NO and the activity of NOS in serum decreased significantly compared with the STZ group in a dose-dependent manner. The activity of SOD in serum and body weight increased significantly compared with the STZ group in a dose-dependent manner. In addition, diabetic rats showed a significant decrease in SOD mRNA expression in pancreatic β cells. However, these changes were reversed by TAP. Histopathological examination also showed the protective effect of TAP on pancreatic β cells.</p><p><b>CONCLUSIONS</b>Triterpenic acid from Prunella vulgaris L. has an anti-diabetic effect, by controlling blood glucose and antioxidants, and has a protective effect on the pancreas.</p>

Effects of ketamine and alcohol on learning and memory impairment in mice / 法医学杂志

OBJECTIVE@#To study the effects of ketamine and alcohol on learning and memory in mice and its possible mechanism.@*METHODS@#Forty mice were divided into 4 groups: normal control group, ketamine group, alcohol group, and alcohol plus ketamine group. Ketamine and alcohol were given by intraperitoneal injection and intragastric administration, respectively, 1 time per day, for 14 days. The ability of learning and memory in mice was tested by the method of step-down and Morris water maze. Acetylcholine (ACh) and 5-hydroxy tryptamine(5-HT) in mice brain tissue were analyzed for the possible mechanism.@*RESULTS@#(1) Step-down: The treatment groups lessened the latency and added wrong times (P < 0.05). The number of errors in the combined treatment group significantly increased comparing with the single drug treatment group (P < 0.05). (2) Morris water-maze: The treatment groups prolonged the latency (P < 0.05), reduced the target quadrant activity time significantly (P < 0.05), and decreased the numbers of crossing the former platform significantly (P < 0.05). (3) Biochemical index determination: The concentrations of ACh and 5-HT in treatment groups decreased significantly (P < 0.05), showed a more decreasement comparing with the single drug treatment group.@*CONCLUSION@#Ketamine has a synergistic effect with alcohol on learning and memory impairment in mice, which may be related to the common inhibitive effect on the ACh and 5-HT.

Effects of ketamine on proliferation and apoptosis of pheochromocytoma cell / 法医学杂志

OBJECTIVE@#To explore the effect of ketamine on adrenal pheochromocytoma (PC12) cell proliferation inhibition and induction of apoptosis and its mechanism.@*METHODS@#PC12 cells of rats were models for dopaminergic neuron. PC12 cells were cultured with ketamine at concentrations of 0.9, 1.2, 1.5, 1.8 and 2.1 mmol/L, respectively. The cell viability was measured by MTT method after incubation at 12, 24, 48 and 72h. Hoechst stain was used to observe the morphological changes of apoptosis. PC12 cells cultured after 48 h with different concentrations of ketamine were selected to detect apoptotic rate using flow cytometry and detect the expression of bax and bcl-2 proteins using Western blotting.@*RESULTS@#For different concentrations of ketamine, vitality of PC12 cells significantly decreased with increase of the incubation time. Apoptosis was obviously observed using Hoechst staining. Flow cytometry showed that apoptosis rates significantly increased with increasing ketamine concentrations.@*CONCLUSION@#Ketamine can inhibit the proliferation of PC12 cell by inducing apoptosis of the PC12 cell in a concentrations-dependent manner. The underlying mechanism may be related to promoting the expression of bax and inhibiting the expression of bcl-2 in the cells.

Ursolic acid induces human hepatoma cell line SMMC-7721 apoptosis via p53-dependent pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Ursolic acid (UA) is a ubiquitous molecule in the plant kingdom with specific anticancer effects that have been shown in vitro and in vivo. Although UA can inhibit the proliferation of liver cancer cells and induce apoptosis of many types of tumor cells, the molecular mechanism of its anti-hepatoma activity is still not well defined. The objective of this study was to investigate the inhibitory effect and mechanisms of UA on the human hepatoma cell line SMMC-7721.</p><p><b>METHODS</b>After treatment with UA, the growth inhibition of SMMC-7721 cells was assessed by MTT assay. Cells were also evaluated by flow cytometric analysis, Wright-Giemasa staining, Hoechst 33258 staining and transmission electron microscope after they were induced by UA. DNA microarray technology was used to investigate the gene expression pattern of SMMC-7721 cells exposed to UA 40 micromol/L. The molecular mechanism of cells death was analyzed by real-time RT-PCR and Western blotting.</p><p><b>RESULTS</b>The proliferation of SMMC-7721 cells was significantly inhibited in a dose- and time-dependent manner after UA treatment. UA induced cell cycle arrest and apoptosis. The DNA microarray analysis indicated that 64 genes were found to be markedly up- or down-expressed, including GDF15, SOD2, ATF3, and fos. The result of Western blotting showed the apoptotic proteins p53 and Bax were up-regulated while the anti-apoptotic protein Bcl-2 was down-regulated. Real-time RT-PCR confirmed UA could up-regulate the mRNA expressions of GDF15, SOD2, ATF3 and down-regulate the mRAN expression of fos. Meanwhile these effects were partly blocked by pretreatment with the p53 inhibitor Pft-alpha.</p><p><b>CONCLUSION</b>Activation of the p53 pathway is involved in UA inhibition of SMMC-7721 human hepatocellular carcinoma cell growth and induction of apoptosis.</p>

Receptor antagonist of NMDA and animal models of schizophrenia / 法医学杂志

Schizophrenia is one of the common mental diseases. Because the mechanism of the schizophrenia is significantly complicated, the cause is still unknown. N-methyl-D-aspartate receptor antagonist can simulate the positive and negative symptoms, as well as the cognitive disorder of schizophrenia. Thus it has been widely used to establish the animal models of schizophrenia. The relationship of the three blocking agents of ion channels (phencyclidine, MK-801, ketamine) and the establishment of schizophrenia animal models is reviewed in this article.

The correlation between ketamine-induced schizophrenia-like signs in mice and the expressions of NRG1, ErbB4 mRNA / 法医学杂志

OBJECTIVE@#To explore the correlation between signs similar to schizophrenia in mice after ketamine administration and the expressions of NRG1 and ErbB4 mRNA in order to explain the possible pathogenesis of schizophrenia.@*METHODS@#Fifty KM mice were randomly divided into 5 groups which were administered intraperitoneally with saline, clozapine and different dosages ketamine. The ketamine groups were administered intraperitoneally with low dosage (25 mg/kg), middle dosage (50 mg/kg) and high dosage (100 mg/kg) one time every day for 7 days. After administration of 100 mg/kg ketamine for 7 days, the clozapine group was introgastrically administered 20 mg/kg with clozapine one time every day for 7 days. The pathological changes of hippocampus neurons were observed by HE stain. The expressions of the NRG1 and ErbB4 mRNA in hippocampus were detected by reverse transcriptase polymerase chain reaction (RT-PCR).@*RESULTS@#In the group with high dosage of ketamine, the levels of NRG1 and ErbB4 mRNA were significantly lower than that of the group with saline.@*CONCLUSION@#Ketamine may induce signs similar to schizophrenia in KM mice. The mechanism may be involved in the reduction of NRG1 and ErbB4 mRNA expression.

Advances in research of ketamine addiction mechanism / 法医学杂志

Ketamine is a phencyclidine derivative acting primarily as a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) excitatory glutamate receptors. As a common intravenous anaesthetic in clinic, it is also increasingly abused because of its hallucination and addiction effects. Based on the pharmacological and toxicologic characteristics of ketamine and the acknowledged addiction mechanism of other abused drugs, this article reviews the possible addiction mechanism of the ketamine in the aspects of its enhanced effects and reward systems, the anatomic structures, the related receptors and the individual differences.

Behavior study of ketamine-induced symptoms similar to schizophrenia in mice / 法医学杂志

OBJECTIVE@#To observe the symptoms similar to schizophrenia in mice after ketamine single or continuous injection and to evaluate the feasibility of schizophrenia model injected with different dose of ketamine.@*METHODS@#A total of 40 male mice were randomly divided into 4 groups, which were injected intraperitoneally with physiological saline (control group), 25 mg/kg ketamine (low dose group), 50 mg/kg ketamine (middle dose group), and 100 mg/kg ketamine (high dose group) qd for 7 days continuously. The behavior changes of mice were observed.@*RESULTS@#Hyperactivity, stereotyped behavior and ataxia (P < 0.01) were observed in high dose group after single injection. After continuous injection of ketamine for 7 days, the middle dose group showed hyperactivity, stereotyped behavior and ataxia (P < 0.05), stereotyped behavior and ataxia were more significant in high dose group (P < 0.01).@*CONCLUSION@#Ketamine can induce the symptoms similar to schizophrenia in mice after single or continuous injection. The symptoms induced by high dose ketamine will be more prominent and stable after continuous injection.

A short-chain alpha-neurotoxin from Naja naja atra produces potent cholinergic-dependent analgesia / 神经科学通报·英文版

Objective To investigate the analgesia induced by cobrotoxin (CT) from venom of Naja naja atra, and the effects of atropine and naloxone on the antinociceptive activity of CT in rodent pain models. Methods CT was administered intraperitoneally (33.3, 50, 75 mu g/kg), intra-cerebral venticularly (2.4 mu g/kg) or microinjected into periaqueductal gray (PAG, 1.2 mu g/kg). The antinoCiceptive action was tested using the hot-plate test and the acetic acid writhing test in mice and rats. The involvement of cholinergic system and the opioid system in CT-induced analgesia was examined by pretreatment of animals with atropine (0.5 mg/kg, im or 10 mg/kg, ip) or naloxone (3 mg/kg, ip). The effect of CT on motor activity was tested using the Animex test. Results CT (33.3, 50 and 75 mu g/kg, ip) exhibited a dosedependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. In the mouse acetic acid writhing test, the intra-cerebral ventricle administration of CT 2.4 mu g/kg (1/23th of a systemic dose) produced marked analgesic effects. Microinjection of CT 1.2 mu g/kg (1/46th of systemic dose) into the PAG also elicited a robust analgesic action in the hot-plate test in rats. Atropine at 0.5 mg/kg (im) or naloxone at 3 mg/kg (ip) failed to block the analgesic effects of CT, but atropine at 10 mg/kg (ip) did antagonize the analgesia mediated by CT in the mouse acetic acid writhing test. At the highest effective dose of antinociception (75 mu g/kg), CT did not change the spontaneous mobility of mice. Conclusion These results suggest that CT from Naja naja atra venom has analgesic effects. Central nervous system may be involved in CT's analgesic effects and the PAG may be the primary central site where CT exerts its effects. The central cholinergic system but not opioid system appears to be involved in the antinociceptive action of CT.

Mitochondrial dysfunction and Huntington disease / 神经科学通报·英文版

Huntington disease (HD) is a chronic autosomal-dominant neurodegenerative disease. The gene coding Huntingtin has been identified, but the pathogenic mechanisms of the disease are still not fully understood. This paper reviews the involvement of mitochondrial dysfunction in pathogenesis of HD.

Analgesic effects of receptin, a chemically modified cobratoxin from Thailand cobra venom / 神经科学通报·英文版

Objective To investigate the analgesia induced by receptin (REC), a chemically modified cobratoxin (CTX, a long-chain postsynaptic alpha -neurotoxin from Thailand cobra venom), and the effects of atropine and naloxone on antinociceptive activity of REC in rodent pain models. Methods REC was administered intraperitoneally (5 mg/kg, 7.07 mg/kg, or 10 mg/kg, i.p.) or intra-cerebral venticularly (62.5 mu g/kg, i.c.v.). The antinociceptive action was determined using the hot-plate test, the acetic acid writhing test and tail flick assay in mice and rats. The involvement of cholinergic and the opioid peptidergic systems in REC-induced analgesia were examined by pretreatment of animals with atropine (Atr; 0.5 mg/kg, i.m. or 10 mg/kg, i.p.) or naloxone (Nal; 3 mg/kg, i.p.). The effect of REC on motor activity was tested using the Animex test in mice. Results REC (5 mg/kg, 7.07 mg/kg or 10 mg/kg, i.p.) exhibited a dose-dependent analgesic action in mice as determined with hot-plate test and acetic acid writhing test. The significant analgesia of REC was seen 2 h to 3 h after its administration. In the rat-tail flick assay, the administration of REC at 62.5 mu g/kg (1/160 of systemic dose; i.c.v.) produced marked analgesic effects. Atropine at 0.5 mg/kg (i.m.), 10 mg/kg (i.p.) or naloxone at 3 mg/kg (i.p.) failed to block the analgesic effects of REC. REC at the highest effective dose of 10 mg/kg did not change the spontaneous mobility of mice. Conclusion These results demonstrate that REC has analgesic effect. This activity appears to be mediated through the peripheral nervous system though central nervous system may contribute to REC' s analgesic effects. The central cholinergic system and opioid peptidergic system appear not to be involved in the antinociceptive action of REC.

Regulatory genes controlling neural stem cells differentiation into neurons / 神经科学通报·英文版

The recent progress in neural stem cells (NSCs) research has shed lights on possibility of repair and restoration of neuronal function in neurodegenerative diseases using stem cells. Induction of stem cells differentiate into mature neurons is critical to achieve the clinical applications of NSCs. At present, molecular mechanisms modulating NSC differentiation are not fully understood. Differentiation of stem cells into neuronal and glial cells involves an array of changes in expression of transcription factors. Transcription factors then trigger the expression of a variety of central nervous system (CNS) genes that lead NSCs to differentiate towards different cell types. In this paper, we summarized the recent findings on the gene regulation of NSCs differentiation into neuronal cells.

Effects of ferulic acid on E-selectin expression in activated endothelial cell and leukocyte-endothelial cell adhesion / 药学学报

<p><b>AIM</b>To study the effects of ferulic acid (FA) on E-selectin expression in human umbilical vein endothelial cells (HUVECs) activated by lipopolysaccharide and leukocyte-endothelial cell adhesion.</p><p><b>METHODS</b>The effects of FA on E-selectin and E-selectin mRNA expression were determined by flow cytometry and reverse transcription polymerase chain reaction. The effect of FA on HL60-HUVEC adhesion was evaluated with the method of staining the cells by Rose Bengal.</p><p><b>RESULTS</b>The expression of E-selectin and E-selectin mRNA were down regulated by FA (0.62 and 0.41 mmol x L(-1), respectively). HL60 cells adhered to activated HUVECs were also reduced by FA (0.62 and 0.41 mmol x L(-1), respectively).</p><p><b>CONCLUSION</b>FA can inhibit the expression of E-selectin and E-selectin mRNA and HL60-HUVEC adhesion. This may contribute to its protective effect against ischemia-reperfusion injury.</p>

Establishment of an imatinib resistant cell line K562/G01 and its characterization / 中华血液学杂志

<p><b>OBJECTIVE</b>To establish a BCR/ABL+ cell line with resistance to imatinib, and investigate the possible mechanisms of the acquired resistance.</p><p><b>METHODS</b>K562 cells were cultured in gradually increased concentrations of imatinib over a period of several months to generate their resistance line. MTT assay, RT-PCR, Western blotting, and FISH were used to study the possible molecular mechanisms of the resistance.</p><p><b>RESULTS</b>A resistant cell line, K562/G01, was established with 15.2 +/- 3.0-fold resistant to imatinib as compared with that of the parental sensitive cell line. The resistant cell line also had the cross-resistance to a broad spectrum of other anticancer agents excepting for DOX. There was no difference between the two cell lines in terms of the cell morphology, proliferation doubling time, and fraction distribution of cell cycle. K562/G01 cells showed increased levels of BCR/ABL, mdr1 mRNA and their coding proteins and the increased tyrosine kinase activity. No point mutation in the BCR/ABL ATP-binding site was detected while the copies of BCR/ABL fusion gene were increased in K562/G01 cells.</p><p><b>CONCLUSION</b>An imatinib-resistant human leukemia cell line, K562/G01, was established. The mechanisms of resistance of K562/G01 cells to imatinib involved increased expression of BCR/ABL and mdr1/P-gp, amplification of BCR/ABL fusion gene, and increased activity of BCR/ABL.</p>

Effects of quercetin on platelet-endothelial cell adhesion and their expression of adhesion molecules / 药学学报

<p><b>AIM</b>To observe the effect of quercetin (Que) on the adhesion of platelets to cultured endothelial cells and adhesion molecule expression by human umbilical vein endothelial cells (HUVEC) and platelets.</p><p><b>METHODS</b>[3H]-Adenine labeled platelets were incubated with HUVEC to investigate the effect of Que on adhesion of platelets to HUVEC. The number of platelets adhering to the HUVEC monolayer was determined by liquid scintillation spectroscopy. TNF-alpha induced HUVEC expression ICAM-1 and thrombin induced platelets expression of P-selectin were measured by flow cytometry.</p><p><b>RESULTS</b>Que (0.3-2.4 mumol.L-1) was shown to inhibit the increase of P-selectin expression of thrombin activated platelets. Pretreatment of HUVEC with tumor necrosis factor (TNF-alpha) significantly increased platelets adhesion to HUVEC and the expression ICAM-1. Que (0.6-2.4 mumol.L-1) inhibited this effect of TNF-alpha in a concentration-dependent manner.</p><p><b>CONCLUSION</b>Que can inhibit the adhesion of platelets to HUVEC and the expression of adhesion molecules (P-selectin and ICAM-1).</p>

Structure-based design, synthesis and evaluation of bioactivity of anti-P-gp peptide mimetic / 药学学报

<p><b>AIM</b>To design and evaluate the small peptide mimetic of anti-P-glycoprotein (P-gp) antibody (PHMA02).</p><p><b>METHODS</b>From the three dementional structure analysis of computer modeling of PHMA02 CDR loops, a small peptide mimetic was designed and determined by flow cytometry.</p><p><b>RESULTS</b>Anti-P-gp peptide mimetic functionally similar to PHMA02 was developed. The peptide mimetic competitively inhibits PHMA02 binding to P-gp and partially block the P-gp function as a drug efflux pump in K562/A02 cells.</p><p><b>CONCLUSION</b>Some special conformational properties of CDR loops of antibody might serve as lead structures for develop new biological peptide mimetics. Antibody-structure-based design would develop new drug in the future.</p>

Effect of xiaoyu tablet on blood flow parameters and morphology of carotid artery in atherosclerotic patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Xiaoyu Tablet (XYT) on blood flow parameters and morphology of carotid artery in atherosclerotic patients.</p><p><b>METHODS</b>Using color Doppler ultrasonographic technique to examine the blood flow parameters and intimal thickness of carotid artery in 20 patients of carotid atherosclerosis after 24 weeks treatment of XYT, and compared with those in 10 patients treated with gastrodine lipid-lowering tablet.</p><p><b>RESULTS</b>After 24 weeks treatment, blood flow parameters of carotid artery were obviously improved and intimal thickness of common carotid arteries in both side was markedly decreased. XYT showed an effect better than that of gastrodine lipid-lowering tablet.</p><p><b>CONCLUSION</b>XYT is effective in increasing blood flow of cervical and cerebral arteries.</p>