The mechanism of the combination of radix ophiopogonis and schisandra chinensis on atherosclerosis based on network pharmacology / 国际中医中药杂志

Objective@#To excavate the mechanism of the combination of Radix Ophiopogonis and Schisandra chinensis to treatatherosclerosisbased on network pharmacology to discuss its mechnism.@*Methods@#This paper excavated the associated proteins with Radix Ophiopogonis and Schisandra chinensis from the TCMGeneDIT database, and constructed the multicomponent protein network of Radix Ophiopogonis, Schisandra chinensis and proteins ApoE-/- mice were randomly divided into control group, model group, low, medium, high dose group and atorvastatin calcium group. Except the control group, other groups were fed with H10540 high fat diet for 12 weeks. From the 4th week, the atrovastatin calcium group was given atrovastatin calcium liquid 6 mg/kg by gavage. The low, medium and high dose groups were administed 4.68, 2.34 and 1.17 g/kg, respectively, once a day by gavage for 8 weeks. The oil red staining was applied to observe the pathological changes of atherosclerotic aortic wall. Western blot was subjected to detect the expression change of mitogen activated protein kinases p38 (p38), ATP binding cassette subfamily G member 1 (ABCG1), Toll like receptor 4 (TLR4), heat shock protein 90 alpha family class a member 1 (HSP90AA1), MMP-9 and arachidonate 5-lipoxygenase (ALOX5) in liver tissue, as well as nuclear factor related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in brain tissue.@*Results@#It was found that eleven components were interacted with 37 proteins, forming a protein interaction network with 48 nodes and 190 boundaries without isolated nodes. Compared to the model group, the level of p-p38/p38 (2.12 ± 0.12, 1.76 ± 0.11, 1.69 ± 0.10 vs. 2.45 ± 0.16), TLR4 (1.98 ± 0.10, 1.64 ± 0.11, 1.55 ± 0.12 vs. 2.68 ± 0.06), HSP90AA1 (1.79 ± 0.10, 1.66 ± 0.09, 1.59 ± 0.11 vs. 2.06 ± 0.07), MMP9 (1.84 ± 0.11, 1.75 ± 0.12, 1.66 ± 0.08 vs. 2.68 ± 0.10) in liver tissue of low, medium and high dose groups significantly decreased, the level of ABCG1 (0.53 ± 0.08, 0.78 ± 0.09, 0.81 ± 0.10 vs. 0.45 ± 0.04), ALOX5 (0.59 ± 0.04, 0.67 ± 0.09, 0.88 ± 0.07 vs. 0.47 ± 0.02) in liver tissue of low, medium and high dose groups significantly increased (P<0.05). The expression of Nrf2 (1.62 ± 0.12, 1.32 ± 0.09, 1.14 ± 0.06 vs. 2.12 ± 0.08) in cytoplasm of brain tissue significantly decreased, and Nrf2 (1.12 ± 0.09, 1.61 ± 0.07, 1.68 ± 0.11 vs. 1.07 ± 0.08) in cell nucleus of brain tissue significantly increased. The expression of HO-1 (1.16 ± 0.09, 1.73 ± 0.11, 1.82 ± 0.08 vs. 1.05 ± 0.04) in brain tissue significantly increased.@*Conclusions@#Network pharmacology and molecular biology were used to elucidate the molecular mechanism of the combination of Schisandra chinensis and Ophiopogon japonicus in the prevention and treatment of atherosclerosis, also to validate the related mechanism via Nrf2 pathway, which provided a reference for the further study of the combined prescription.

The mechanism of the combination of radix ophiopogonis and schisandra chinensis on atherosclerosis based on network pharmacology / 国际中医中药杂志

Objective:To excavate the mechanism of the combination of Radix Ophiopogonis and Schisandra chinensis to treatatherosclerosisbased on network pharmacology to discuss its mechnism.Methods:This paper excavated the associated proteins with Radix Ophiopogonis and Schisandra chinensis from the TCMGeneDIT database, and constructed the multicomponent protein network of Radix Ophiopogonis, Schisandra chinensis and proteins ApoE-/- mice were randomly divided into control group, model group, low, medium, high dose group and atorvastatin calcium group. Except the control group, other groups were fed with H10540 high fat diet for 12 weeks. From the 4th week, the atrovastatin calcium group was given atrovastatin calcium liquid 6 mg/kg by gavage. The low, medium and high dose groups were administed 4.68, 2.34 and 1.17 g/kg, respectively, once a day by gavage for 8 weeks. The oil red staining was applied to observe the pathological changes of atherosclerotic aortic wall. Western blot was subjected to detect the expression change of mitogen activated protein kinases p38 (p38), ATP binding cassette subfamily G member 1 (ABCG1), Toll like receptor 4 (TLR4), heat shock protein 90 alpha family class a member 1 (HSP90AA1), MMP-9 and arachidonate 5-lipoxygenase (ALOX5) in liver tissue, as well as nuclear factor related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in brain tissue.Results:It was found that eleven components were interacted with 37 proteins, forming a protein interaction network with 48 nodes and 190 boundaries without isolated nodes. Compared to the model group, the level of p-p38/p38 (2.12 ± 0.12, 1.76 ± 0.11, 1.69 ± 0.10 vs. 2.45 ± 0.16), TLR4 (1.98 ± 0.10, 1.64 ± 0.11, 1.55 ± 0.12 vs. 2.68 ± 0.06), HSP90AA1 (1.79 ± 0.10, 1.66 ± 0.09, 1.59 ± 0.11 vs. 2.06 ± 0.07), MMP9 (1.84 ± 0.11, 1.75 ± 0.12, 1.66 ± 0.08 vs. 2.68 ± 0.10) in liver tissue of low, medium and high dose groups significantly decreased, the level of ABCG1 (0.53 ± 0.08, 0.78 ± 0.09, 0.81 ± 0.10 vs. 0.45 ± 0.04), ALOX5 (0.59 ± 0.04, 0.67 ± 0.09, 0.88 ± 0.07 vs. 0.47 ± 0.02) in liver tissue of low, medium and high dose groups significantly increased ( P<0.05). The expression of Nrf2 (1.62 ± 0.12, 1.32 ± 0.09, 1.14 ± 0.06 vs. 2.12 ± 0.08) in cytoplasm of brain tissue significantly decreased, and Nrf2 (1.12 ± 0.09, 1.61 ± 0.07, 1.68 ± 0.11 vs. 1.07 ± 0.08) in cell nucleus of brain tissue significantly increased. The expression of HO-1 (1.16 ± 0.09, 1.73 ± 0.11, 1.82 ± 0.08 vs. 1.05 ± 0.04) in brain tissue significantly increased. Conclusions:Network pharmacology and molecular biology were used to elucidate the molecular mechanism of the combination of Schisandra chinensis and Ophiopogon japonicus in the prevention and treatment of atherosclerosis, also to validate the related mechanism via Nrf2 pathway, which provided a reference for the further study of the combined prescription.

Correction to: Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg mice

In the original publication Fig. 1D and supplementary material is incorrect. The correct figure and supplementary material is provided in this correction.

Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg mice

Recently we have established a new culture condition enabling the derivation of extended pluripotent stem (EPS) cells, which, compared to conventional pluripotent stem cells, possess superior developmental potential and germline competence. However, it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment. Here, we show that EPS cells can be robustly generated from non-permissive NOD-scid Il2rg mice through de novo derivation from blastocysts. Furthermore, these cells can also be efficiently generated by chemical reprogramming from embryonic NOD-scid Il2rg fibroblasts. NOD-scid Il2rg EPS cells can be expanded for more than 20 passages with genomic stability and can be genetically modified through gene targeting. Notably, these cells contribute to both embryonic and extraembryonic lineages in vivo. More importantly, they can produce chimeras and integrate into the E13.5 genital ridge. Our study demonstrates the feasibility of generating EPS cells from refractory mouse strains, which could potentially be a general strategy for deriving mouse pluripotent cells. The generation of NOD-scid Il2rg EPS cell lines permits sophisticated genetic modification in NOD-scid Il2rg mice, which may greatly advance the optimization of humanized mouse models for biomedical applications.

MiR-124 involves in methamphetamineaddiction in PC12 cells by inhibiting GluR2 / 中国药理学通报

Aim To investigate the change of miR-124 expression in methamphetamine-induced addiction in PC12 cells and the possible regulatory mechanism that it involves.Methods PC12 cells were randomly divided into 6 groups as follows: control group, methamphetamine group, agomir Negative Control group, miR-124 agomir group, agomir Negative Control+methamphetamine group and miR-124 agomir+methamphetamine group.After the treatment, the total RNA and protein were extracted in PC12 cells.The expression of miR-124 was measured by Real-time PCR and the expression of GluR2 was determined by Western blot in PC12 cells.Results Compared with those in the control group, the expression of miR-124 was remarkably decreased and the expression of GluR2 was significantly increased in the methamphetamine group in PC12 cells.Compared with those in the agomir Negative Control+methamphetamine group, the expression of miR-124 was remarkably increased and the expression of GluR2 was significantly decreased in the miR-124 agomir+methamphetamine group in PC12 cells.Conclusion MiR-124 might involve in methamphetamine-induced addiction in PC12 cells by inhibiting GluR2.

OATP1B1 in drug-drug interactions between traditional Chinese medicine Danshensu and rosuvastatin / 药学学报

The study was designed to explore the drug-drug interactions mechanisms mediated by OATP1B1 between traditional Chinese medicine Danshensu and rosuvastatin. First, the changes of rosuvastatin pharmacokinetics were investigated in presence of Danshensu in rats. Then, the primary rat hepatocytes model was established to explore the effects of Danshensu on the uptake of rosuvastatin by hepatocytes. Finally, HEK293T cells with overexpression of OATP1B1*a and OATP1B1*5 were established using a lentiviral delivery system to explore the effects of Danshensu on the uptake of rosuvastatin. Rosuvastatin pharmacokinetic parameters of C(max0, AUCO(0-t), AUC(0-∞) were increased about 123%, 194% and 195%, by Danshensu in rats, while the CL z/F value was decreased by 60%. Uptake of rosuvastatin in the primary rat hepatocytes was decreased by 3.13%, 41.15% and 74.62%, respectively in the presence of 20, 40 and 80 μmol x L(-1) Danshensu. The IC50 parameters was (53.04 ± 2.43) μmol x L(-1). The inhibitory effect of Danshensu on OATP1B1 mediated transport of rosuvastatin was related to the OATP1B1 gene type. In OATP1B1*5-HEK293T mutant cells, transport of rosuvastatin were reduced by (39.11 ± 4.94)% and (63.61 ± 3.94)%, respectively, by Danshensu at 1 and 10 μmol x L(-1). While transport of rosuvastatin was reduced by (8.22 ± 2.40)% and (11.56 ± 3.04)% and in OATP1B1*1a cells, respectively. Danshensu significantly altered the pharmacokinetics of rosuvastatin in rats, which was related to competitive inhibition of transport by OATPJBI. Danshensu exhibited a significant activity in the inhibition of rosuvastatin transport by OATP1B1*5-HEK293T, but not by OATP1B1*1a, suggesting a dependence on OATP1B1 sequence.

Study on the neuroprotective effects and action mechanisms of four Chinese herbal ;monomer on cerebral ischemia reperfusion mice / 国际中医中药杂志

Objective To compare the therapeutical effect of puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A on cerebral ischemia reperfusion mice. Methods The mice were randomly assigned for sham group, model group, puerarin group, ligustrazine group, ginsenoside Rb1 group, and Hydroxysafflor yellow A group, 24 mice for each group. All the groups were subjected to middle cerebral artery occlusion (MCAO) by 1 h ischemia and 24 h of reperfusion except the sham group. The puerarin, ligustrazine, ginsenoside Rb1, Hydroxysafflor yellow A were administrated by tail vein injection with 3μmol/kg at the onset of 1 h of ischemia. The neurologic deficit score, infarct area calculated by TTC staining, cerebral cortex blood flow monitored by laser doppler flowmetry, NO content measured by chemical colorimetry and western blot were applied to determine the expression for cleaved-caspase-3 and nuclear transcription factor NF-κB for each group. Results Compared with the model group, the infarct area (15.83%± 1.83%, 22.00%± 2.53%, 22.83%± 1.83%, 17.83%± 1.72%vs. 34.67%± 2.66%) in the puerarin group, ligustrazine group, ginsenoside Rb1 group, Hydroxysafflor yellow A group was significantly decreased (P<0.01 or P<0.05);the cerebral cortex blood flow (598.81 ± 9.90 μl/kg?min-1, 614.78 ± 9.20 μl/kg?min-1, 577.83 ± 5.55 μl/kg?min-1, 583.54 ± 7.98 μl/kg?min-1 vs. 548.43 ± 1.97 μl/kg?min-1) significantly increased (P<0.01 or P<0.05);the NO content (17.09 ± 1.18μmol/L, 18.54 ± 0.54μmol/L, 18.17 ± 0.49μmol/L, 15.10 ± 0.73μmol/L vs. 20.63 ± 0.73μmol/L) ignificantly decreased (P<0.01 or P<0.05);the expression of cleaved-caspase-3 (1.02 ± 0.08, 1.12 ± 0.04, 0.87 ± 0.08, 1.07 ± 0.08 vs. 1.30 ± 0.06) and NF-κB p-p65/NF-κB p65 (1.03 ± 0.19, 1.15 ± 0.05, 1.12 ± 0.08, 0.72 ± 0.08 vs. 1.45 ± 0.08) ignificantly decreased (P<0.01 or P<0.05) Conclusions Four Chinese herbal monomers could improve nerve and cerebral dysfunctions and ameliorate ischemia symptoms with varying degrees. The mechanisms were involved with the enhancement of cerebral cortex blood flow and inhibition of cell apoptosis and the activation of inflammatory signaling pathways.

Study on the Irrational Prescription and Medical Orders and Interventions in Our Hospital / 中国药房

OBJECTIVE:To promote rational drug use clinically. METHODS:Sampling rate of prescriptions in outpatient and emergency departments was no less than 1‰ of total prescriptions and no less than 100 prescriptions were reviewed every month;the sampling rate (according to the hospital records of discharge) of ward (district) doctor’s advice was no less than 1% and no less than 30 prescriptions were reviewed every month. According to drugs evaluation indicators of rational drug use,the prescrip-tions were analyzed statistically,immediate intervention and administrative intervention were adopted for irrational prescriptions and medical orders. RESULTS:The average qualified rate of outpatient prescriptions was 97.86%and 0.92%was non-standard prescrip-tions,1.20% was inappropriate prescriptions and 0.01% was extraordinary prescriptions. The non-standard prescriptions in the sec-ond half year were significantly lowered,with statistical significance(P<0.05). The inappropriate usage and dosage was not effec-tively controlled. The average qualified rate of medical orders was 96.30% and drug replacement withont any reference and incom-plete diagnosis in the second half year were significantly lowered,with statistical significance(P<0.05). The utilization rate of an-tibiotics in emergency department was 41.51%and the other indicators were basic standard. The qualified rate of Majing drugs’pre-scriptions was 81.60%and non-standard prescriptions accounted for 88.37%in the irrational prescriptions. CONCLUSIONS:Imme-diate intervention and administrative intervention have achieved some success. Immediate intervention has mainly reduced the non-standard prescriptions and administrative intervention has controlled some specific irrational prescriptions.