Effect of Picroside II on ERK1/2 Signal Pathway in Cerebral lschemic Injury Rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the neuroprotective effect and mechanism of picroside II on extracellular regulated protein kinases1/2 (ERK1/2) signal transduction pathway in cerebral ischemia injuryrats. METHODS The middle cerebral artery occlusion (MCAO) model was established by inserting a monofilament into middle cerebral artery. Totally 96 successfully modeled Wistar rats were divided into the modelgroup, the treatment (picroside II) group, the Lipopolysachcaride (LPS) group, and the U0126 group according to random digit table. Each group was further divided into 3 subgroups, i.e. 6, 12, and 24 h sub-groups. Picroside II (20 mg/kg) was peritoneally injected to rats in the treatment group 2 h after ischemia.LPS (20 mg/kg) and Picroside II (20 mg/kg) were peritoneally injected to rats in the LPS group 2 h after ischemia. U0126-EtOH (20 mg/kg)and Picroside II (20 mg/kg) were peritoneally injected to rats in the U0126group 2 h after ischemia. Equal volume of normal saline was peritoneally injected to rats in the control groupand the model group. The neurobehavioral function was evaluated by modified neurological severity score(mNSS) test. The structure of neurons was observed using hematoxylin-eosinstaining (HE) staining. Theapoptotic cells were detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The expression of phosphorylated extracellular signal-regulated protein kinase1,2 (pERK1,2) in cortex was detected using immunohistochemistry (IHC) and Western blot.</p><p><b>RESULTS</b>After cerebral ischemia injury neurological impairment score increased, the damage of neuron in the cortical area was aggravated, apoptotic cells increased in the model group as time went by. The expression of pERK1/2 increased more significantly in the model group than in the control group (P <0.05). The damage of neuron in the cortical area was milder, while apoptotic cells decreased, the expression of pERK1f2 obviously decreased more in the treatment group and the U0126 group (P < 0.05). The early damage of neuron in the cortical area was more severe, apoptotic cells and the expression of pERK12 were comparatively higher in early stage of the LPS group, but the expression of pERK1/2 was somewhat decreased in late stage.</p><p><b>CONCLUSIONS</b>Activating ERK12 pathway could mediate apoptosis and inflammatory reactions of neurons after cerebral ischemia injury. Picroside II could protect the nerve system possibly through reducing activation of ERKI2 pathway, inhibiting apoptosis of neurons and inflammation reaction.</p>

Effect of tagalsin on p53 and Bcl-2 expression in hepatoma H(22) tumor-bearing mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the effect and mechanism of tagalsin on hepatoma cells.</p><p><b>METHODS</b>The animal models were established by transplanting H(22) mouse hepatoma cells to mouse liver, and ten days later the mice were randomly divided into five groups: blank group, carmofur positive group and tagalsin groups, including low-dose, middle-dose and high-dose groups. Then medicine or oil was given to the mice by gastric gavage in consecutive 5 days with a 2-days interval as a course of treatment, two courses in all. All mice were killed at 24 hours after medication, and the survival period, ascites conditions, aggressive conditions intra- or extra-liver, weight changes, tumor volume and spleen index of the tumor-bearing mice were observed. Pathological changes of the tumors were examined. Apoptotic factors p53 and Bcl-2 protien and mRNA were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>tagalsin inhibited the hepatoma growth effectively without influencing spleen index to some extent. The tumor inhibition rate of tagalsin low, middle and high dose groups were 17.9%, 63.1% and 71.8%, respectively. Immunohistochemical results showed that the p53 and Bcl-2 protein positive cell counts of the positive control and experimental groups were significantly lower than those of the blank group (P < 0.01). RT-PCR results showed that the p53 mRNA expression was significantly enhanced and Bcl-2 mRNA expression was decreased in the positive control groups and tagalsin treatment groups, especially in the high dose group, compared with those of the blank group (P < 0.05).</p><p><b>CONCLUSIONS</b>tagalsin can inhibit the growth of mouse hepatoma cells significantly. The mechanism of its anti-tumor effect may work via up-regulating the wild type p53 gene expression and down-regulating Bcl-2 gene expression and thus regulating tumor cell apoptosis.</p>

Effect of picroside II on expressions of TLR4 and NFkappaB in rats with cerebral ischemia reperfusion injury / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effects of picrodide II on the expressions of Toll-like receptor 4 (TLR4) and nuclear transcription factor kappaB (NFkappaB) in brain tissue of rat after cerebral ischemic reperfusion (I/R) injury.</p><p><b>METHODS</b>Ten rats from 60 adult healthy female Wistar rats received sham-operation were set as the sham-operative group. Established as middle cerebral I/R model (MCAO/R) by thread tying method, the 30 successfully modeled rats were equally randomized into the negative control group, the positive control group and the treatment group. Besides, rats in the treatment group and the positive control group were respectively intervened with picrodide II (10 mg/kg) and salvianic acid A sodium (10 mg/kg) via caudal vein injection before I/R injury, while rats in the sham-operative group and the negative group were injected with equal volume of 0.1 mol/L PBS. Immunohistochemistry stain was used to determine the expressions of TLR4 and NFkappaB, and the apoptotic cells were counted by TUNEL-immunofluorescence assay.</p><p><b>RESULTS</b>In the sham-operative group, the TLR4 and NFkappaB expressed weakly with few TUNEL positive cells scattering in the cortex, striatum and hippocampus. As compared with the sham-operative group, TLR4 and NFkappaB in the negative control group were significantly higher both in absorption A) value and cell number (P < 0.05). In the treatment group and the positive control group, the expressions of TLR4 and NFkappaB and the number of TUNEL positive cells were significantly lower than those in the negative control group (P < 0.05), but no significant difference was shown between the two treated groups (P > 0.05).</p><p><b>CONCLUSIONS</b>Picroside II could down-regulate the expressions of TLR4 and NFkappaB, and inhibit the inflammatory response induced apoptosis in cerebral I/R injured rats.</p>