Biochemical pathways in the antiatherosclerotic effect of berberine.

BACKGROUND: This study investigated the inhibitory effect of berberine (BBR) on lipopolysaccharide (LPS) induced cyclooxygenase-2 (COX-2) expression via the mitogen activated protein kinase (MAPK) signalling cascade pathways in human peripheral blood monocytes (PBMC). METHODS: PBMC from whole blood were isolated and cultured for up to 24 hours after division into 5 groups treated with LPS, LPS + BBR 25 micromol/L, LPS + BBR 50 micromol/L or LPS + BBR 100 micromol/L and untreated. Monocytes were extracted for RT-PCR and Western blot analyses to examine COX-2 mRNA and protein activated expression of p38 mitogen activated protein kinase (p38MAPK), Jun N-terminal kinase (JNK) and extracellular regulated kinases 1/2 (ERK1/2) signalling pathways. RESULTS: COX-2 mRNA and protein expression decreased to a minimum at 12 hours after BBR treatment (P < 0.05). With the increasing concentration of BBR treatment, the COX-2 expression decreased progressively (P < 0.01). With BBR treatment for 6, 12 or 24 hours at three doses, ERK1/2 protein expression was significantly inhibited. For the JNK pathway, only with the treatment of BBR at the concentration of 100 micromol/L was JNK protein expression inhibited compared with the LPS stimulation group (P < 0.01). Irrespective of the BBR concentration, no difference was shown between the BBR group and the LPS group for p38MAPK protein expression. Human monocytes COX-2 mRNA, by RT-PCR, and protein expression, by Western blot analysis, were inhibited when incubated with PD98059, SP600125 and SB203580 (P < 0.05). CONCLUSIONS: Berberine inhibits COX-2 expression via the ERK1/2 signalling pathway and, possibly, at a high dosage via the JNK pathway. P38MAPK may have no relationship with the effect of BBR in PBMC. Berberine inhibited COX-2 mRNA and protein expression in a dose dependent manner and suppressed COX-2 expression to a minimal level after 12 hours of berberine treatment.

Peripheral electrical stimulation reversed the cell size reduction and increased BDNF level in the ventral tegmental area in chronic morphine-treated rats.

Chronic morphine administration induces functional and morphological alterations in the mesolimbic dopamine system (MLDS), which is believed to be the neurobiological substrate of opiate addiction. Our previous studies have demonstrated that peripheral electrical stimulation (PES) can suppress morphine withdrawal syndrome and morphine-induced conditioned place preference (CPP) in rats. The present study was designed to investigate if PES could reverse the cell size reduction induced by chronic morphine treatment in the ventral tegmental area (VTA), which is an important area of the MLDS. Immunohistochemical observations showed that the cell size of dopaminergic neurons in the VTA reduced significantly in the chronic morphine-treated rats with a concomitant decrease in the number of BDNF-positive cells compared to the saline-treated rats. A much milder morphological change, accompanying with an increased number of BDNF-positive cells, was observed in dopaminergic neurons in the rats that received repeated 100 Hz PES after morphine withdrawal. In another experiment, enzyme-linked immunosorbent assay (ELISA) reconfirmed a significant up-regulation of BDNF protein level in the VTA in the rats received 100 Hz PES after morphine abstinence. These results indicate that PES could facilitate the morphological recovery of the VTA dopaminergic cells damaged by chronic morphine treatment and up-regulate the BDNF protein level in the VTA. Activation of endogenous BDNF by PES may play a role in the recovery of the injured dopaminergic neurons in the morphine addictive rats.

A comparison between spontaneous electroencephalographic activities induced by morphine and morphine-related environment in rats.

Previous studies demonstrated that drug cues could elicit drug-like or withdrawal-like effect, both subjectively and physiologically. However, few studies have compared the central activities induced by a drug-related environment and the drug itself. The aim of this study was to observe and compare electroencephalographic (EEG) changes induced by acute morphine administration and by the morphine-related environment. EEG activities were recorded via twelve skull electrodes scattered on the left and right cortex in conscious, freely moving rats, either after acute morphine administration or after successful training of conditioned place preference. Acute administration of morphine (0.1, 0.5, 1, 5, 10, 20 mg/kg, i.p.) produced an increase in absolute EEG power in the delta, theta, alpha1, alpha2, beta1, and beta2 bands, as well as a decrease in the gamma band. Topographic mapping revealed a maximal increase in the lateral leads in the theta band and a maximal change in the centro-frontal region in the remaining bands. After place conditioning training, the morphine-related environment induced a diffuse decrease in absolute power in the delta, theta, alpha1, alpha2, beta1, and beta2 bands, which was opposite to the changes induced by acute morphine administration. In addition, the changes in relative power induced by the two situations also diverged. These results indicate that the central mechanisms underlying the motivation of morphine-induced place preference may be somehow different from those underlying the reward effects produced by acute morphine administration.

Effects of aspirin on atherosclerosis and the cyclooxygenase-2 expression in atherosclerotic rabbits.

BACKGROUND: Atherosclerosis is a complex vascular inflammatory disease. Aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. In this study, the effectiveness of aspirin in suppressing atherosclerosis and the inflammation process was evaluated in rabbits fed with a high fat diet. METHODS: Eighteen male New Zealand rabbits were randomly divided into 3 groups: control group, untreated cholesterol-fed group, aspirin treated cholesterol-fed group, which were fed for 12 weeks. After 12 weeks, the aorta was harvested for pathologic morphology observation. Immunohistochemical analysis of cyclooxygenase-2 (COX-2), macrophage and vascular smooth muscle cell (VSMC) was performed. The statistical analysis was performed by the statistical program SPSS10.0. RESULTS: The aorta plaque/intima size (P/I) by pathologic morphology observation was 0%, (59.6 +/- 13.7)% and (36.3 +/- 16.5)% in the control, untreated cholesterol-fed group and aspirin treated group, respectively. The maximum plaque thickness, the degree of artery stenosis and the proportion of the intimal circumference occupied by atheroma of the 3 groups were significantly different from each other (P < 0.01). The expression of COX-2 and macrophage in plaque of the aspirin treated group were decreased compared with that in untreated cholesterol-fed group. However, no difference was found in the expression of VSMC between the aspirin treated and the untreated cholesterol-fed group. CONCLUSION: The mechanism of atherosclerosis suppression by aspirin in cholesterol-fed rabbits is related to the inhibition of COX-2 expression together with the reduced inflammation followed by, but not related to the hypolipidemic effects.

[Processing of spatial information by hippocampal place cells].

Hippocampal place cells can process the environmental inputs and make up a cognitive map in the hippocampus, or strengthen the synaptic connections within an association cortical cell assembly,thus creating a permanent engram for a spatial site. Outputs from the hippocampus are then integrated with other inputs within the nucleus accumbens and finally initiate a goal-directed behavior through the motor circuit.

Meta-analysis of defibrase in treatment of acute cerebral infarction.

BACKGROUND: Fibrinogen-depleting agents are promising in the treatment of cerebral ischemic disease. They were studied by many trials, and the outcomes were different because of different regimens and different doses. In this study, we assessed the efficacy and safety of defibrase on acute cerebral infarction in China. METHODS: A search using Chinese hospital knowledge database (CHKD) and MEDLINE database for randomized controlled trials was carried out. A CHKD (1994 June 2005) search was performed with the keyword "defibrase", then a second search for the keyword "acute cerebral infarction"; a MEDLINE search (1950 June 2005) was performed with the following keywords: [(cerebral ischemia), OR (acute cerebral infarction), OR (stroke)], AND [defibrase]. Meta-analysis was performed with RevMan software 4.2. RESULTS: Included were 14 studies comparing the efficiency and safety of defibrase with other drugs in the treatment of acute cerebral infarction. Patients' records were pooled (total 646 patients; defibrase, n = 328, no defibrase n = 318). Neurological deficit score (NDS) before treatment showed weighted mean differences (WMD) = 0.95, 95% confidence interval (CI) = (-0.60, 2.50), P = 0.23; NDS after treatment showed WMD = -2.20, 95% CI = (-4.21, -0.18), P = 0.03; Barthel index at 3 months showed WMD = 4.45, 95% CI = (-0.13, 9.03), P = 0.06; the plasma fibrinogen level before treatment showed WMD = 0.02, 95% CI = (-0.16, 0.19), P = 0.86; plasma fibrinogen level after treatment showed WMD = -1.51, 95% CI = (-1.88, -1.15), P < 0.00 001. CONCLUSIONS: With the given dose and regimen of defibrase in China, defibrase may play a role of anticoagulation. It might inhibit the progression of stroke and prevent the recurrence of stroke.

[Effect of ileocecum interposition graft as pylorus replacement on glycometabolism].

OBJECTIVE: To evaluate the application of ileocecum interposition (ii) graft as pylorus replacement in alimentary reconstruction. METHODS: Twenty- one minipigs were randomly divided into three groups: sham operation group (control group), B - i group and ii group. The levels of blood glucose were measured by quick blood glucose testing of paper at 0, 30, 60, 90, and 120 minutes of oral glucose after 60 and 120 post- operative days to compare gastric emptying of liquid feeds. RESULTS: Two months after operation,the peak of blood glucose was (7.8+/- 1.0)mmol/ L, (7.1+/- 0.8)mmol/ L, (4.1+/- 0.4)mmol/ L in B - i, ii group and control group respectively, there were significant differences between the two operation groups and control group (P< 0.01). Four months after operation, the peak of blood glucose was (6.9+/- 1.0) mmol/ L, (5.2+/- 0.8)mmol/ L, (4.2+/- 0.5)mmol/ L, respectively, there was no significant difference between ii group and control group (P > 0.05),but there were significant differences between both of the above two groups and B - i group (P< 0.01). CONCLUSION: The ileocecum interposition graft can offer specific advantages over current reconstruction procedures.