To study the protective effect of combined administration of active ingredients of Danhong on cultured primary mice's brain microvascular endothelial cells (rBMECs) injured by hypoxia. Primary mice's brain micro-vascular endothelial cells were cultured to establish the 4 h hypoxia model. Meanwhile, active ingredients (protocatechuic aldehyde, salvianolic acid B, hydroxysafflor yellow A and tanshinol) of Danhong were administered in rBMECs. The non-toxic dosage was determined by MTT. The leakage of lactate dehydrogenase(LDH), cell superoxide dismutase (SOD) activity and MDA level were detected by the colorimetric method. The expressions of ICAM-1, MMP-9, P53 mRNA were detected by RT-PCR method. Changes in rBMECs cell cycle and early apoptosis were detected by flow cytometry. Danhong's active ingredients and prescriptions 1, 2, 3, 7, 8, 9 could be combined to significantly restrain LDH in hypoxic cells supernatant. Prescriptions 1, 2, 3, 7, 8, 9 could significantly enhance SOD activity in anoxic cells; Prescriptions 1, 2, 3, 8, 9 could significantly decrease the MDA level; Prescriptions 1, 2, 6, 7, 9 could significantly inhibit the early rB-MECs apoptosis induced by hypoxia. After hypoxia, the up-regulated P53 mRNA expression could cause retardation in G, phase and promote cell apoptosis. This proved that the regulatory function of P53 gene lay in monitoring of calibration points in G, phase. Prescriptions 1, 2, 5, 6, 7, 8, 9 could significantly down-regulate the P53 mRNA expression; Prescriptions 1, 4, 7, 8, 9 could significantly down-regulate the ICAM-1 mRNA expression; Prescriptions 1, 3, 6, 9 could significantly down-regulate the MMP-9 mRNA expression. The combined administration of Danhong's active ingredients showed a significant protective effect on primary cultured rBMECs injury induced by hypoxia Its mechanism may be related to the enhancement of cellular antioxidant capacity and the inhibition of inflammatory response and cell apoptosis. This study could provide ideas for researching prescription compatibility, and guide the clinical medication.
Animals ; Apoptosis ; drug effects ; Brain ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Endothelial Cells ; drug effects ; Hypoxia ; drug therapy ; Microvessels ; drug effects ; Rats ; Rats, Sprague-Dawley

Acetylcholine ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Female ; Gardenia ; chemistry ; Maze Learning ; drug effects ; Nitric Oxide ; metabolism ; Ovariectomy ; Plant Extracts ; pharmacology ; Rats ; Thuja ; chemistry ; Ziziphus ; chemistry

Adolescent ; Altitude ; Brain ; drug effects ; Codonopsis ; chemistry ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Tablets

OBJECTIVETo construct multifunctonal nano-delivery system crossing the blood brain barrier (BBB).

METHODSThe magnetic nanoparticles were preprared with O-carboxylmethylated chitosan (O-CMC) and conjugated with a peptide sequence from the human immunodeficiency virus 1-tat protein and transferrin (Tf), and anti-tumor drug methotrexate (MTX), and thus constructed a O-CMC magnetic nanoparticles carrier system conjugating with Tat and Tf (O-MNPs-Tat-Tf) that combines multiple functions including crossing BBB, magnetism, receptor-mediated dual targets and anti-tumor capabilities. The appearance, diameter, and magnetism of MTX-O-MNPs-Tat-Tf carrier system were characterized with transmission electronic microscopy, atomic force microscopy and vibrating samples magnetometer. The cytotoxicity of MTX-loaded O-MNPs-Tat-Tf was investigated with C6 glioma cells. The ability of O-MNPs-Tat-Tf crossing BBB was investigated in rats by single photon emission computed tomography.

RESULTSThe mean particle diameter was 75 nm, along with good anti-tumor property. The multi-functioned carrier system successfully crossed the BBB in rat.

CONCLUSIONThe establishment of MTX-O-MNPs-Tat-Tf carrier model implies a promising future for its application in therapy of cerebral diseases.

Blood-Brain Barrier ; drug effects ; metabolism ; Chitosan ; analogs & derivatives ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Humans ; Magnetics ; Nanoparticles ; Transferrin

AIM: To evaluate the effect of Ocimum sanctum leaf extract on the dietary supplementation in the transgenic Drosophila model of Parkinson's disease. METHOD: The effect of Ocimum sanctum leaf extract was studied on the transgenic Drosophila model of flies expressing normal human alpha synuclein (h-αs) in the neurons. O. sanctum extract at final concentrations of 0.042 8 × 10(-4), 0.87 × 10(-4), and 1.85 × 10(-4) g·mL(-1) of diet were established and the flies were allowed to feed for 21 days. The climbing assay and lipid peroxidation were taken as parameters for the study. RESULTS: The supplementation of O. sanctum extract showed a dose-dependent significant delay in the loss of climbing ability and reduction in oxidative stress in the brain of PD model flies. CONCLUSION The results of the present study showed that the O. sanctum extract is potent in reducing the PD symptoms in transgenic Drosophila model.
Animals ; Brain ; drug effects ; metabolism ; Dietary Supplements ; analysis ; Disease Models, Animal ; Drosophila ; drug effects ; genetics ; metabolism ; Humans ; Lipid Peroxidation ; drug effects ; Ocimum ; chemistry ; Oxidative Stress ; drug effects ; Parkinson Disease ; drug therapy ; metabolism ; Plant Extracts ; administration & dosage ; Plant Leaves ; chemistry

OBJECTIVETo investigate the effects of pyrethroids on the concentrations of thyroid hormone in rat brain.

METHODPermethrin (PM) and deltamethrin (DM) were administered to the rats with daily doses of 100, 200 and 400 mg.kg-1.d-1 and 6.25, 12.5 and 25 mg.kg-1.d-1, respectivelly for 15 days. Serum and brain tissue determinations of thyroxin (T4) and triiodothyronine (T3) were performed by radioimmunoassay (RIA).

RESULTSPM induced a dose dependent decrease in the serum levels of T4, T3, fT4 and fT3 and an increase in the serum TSH levels, whereas DM was only able to induce a dose dependent decrease in the serum levels of T4. PM treatment reduced both the levels of T4 and T3 in homogenates of the cerebral cortex and hippocampus respectively, whereas the highest dose of DM decreased only the cerebral cortex levels of T4. The effects of subchronic treatment with PM and DM on the concentrations of T3 were further investigated in the subcellular fractions, namely nuclei, mitochondria, myelin and synaptosomes of the cerebral cortex and hippocampus. PM treatment induced a decrease in the nuclear and synaptosomal concentrations of T3 of either the cerebral cortex or hippocampus, whereas DM reduced the levels of T3 especially in the mitochondria of the cortex and hippocampus.

CONCLUSIONSTreatment with pyrethroids subchronically to the rats would affect the serum and brain tissue levels of T4 and T3. These results indicate that the pyrethroids-induced neurotoxicity may involve at least in part an impairment of the physiological action of T3 at its subcellular targets.

Animals ; Brain Chemistry ; drug effects ; Cell Nucleus ; chemistry ; drug effects ; Dose-Response Relationship, Drug ; Insecticides ; toxicity ; Nitriles ; toxicity ; Permethrin ; toxicity ; Pyrethrins ; toxicity ; Radioimmunoassay ; Rats ; Synaptosomes ; chemistry ; drug effects ; Thyroid Hormones ; analysis ; blood

OBJECTIVETo study the effects of Naoan tablets on brain hemodynamics and cerebral microcirculation of soft membrane.

METHODCerebral blood stream flux, resistance of blood vessels, blood pressure and heart rate were used as observation indexes in hemodynamics experiment. Artery caliber and the number of capillaries with recovered blood stream were used as observation indexes in microcirculation experiment.

RESULTNaoan tablets at dose of 0.5 g x kg(-1) and 1.0 g x kg(-1) could enhance cerebral blood stream flux, decrease resistance of blood vessels, and reduce blood pressure. While no effects on heart rate. Naoan tablet at dose of 0.7 g x kg(-1) and 2.1 g x kg(-1) could increase the number of capillaries with recovered blood stream and enlarge the artery caliber of soft membrane in rats.

CONCLUSIONNaoan tablets can improve the indexes of hemodynamics and cerebral microcirculation of soft membrane.

Anesthesia ; Animals ; Brain ; blood supply ; Cerebrovascular Circulation ; drug effects ; Codonopsis ; chemistry ; Dogs ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Female ; Ligusticum ; chemistry ; Male ; Microcirculation ; drug effects ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Wistar ; Tablets ; Vascular Resistance ; drug effects

OBJECTIVETo investigate the effects of Aloe vera extract (AV) on mitochondria in rat pheochromocytoma (PC12) cells and rat brain and to study the mechanism of its neuroprotection.

METHODAfter treatment, the morphology of PC12 cells was observed under microscope, the activity of mitochondria in PC12 cells was measured by MTT method, and the mitochondrial membrane potential (MMP) in PC12 cells was detected by JC-1 method. The mitochondrial function in rat brain was detected by resazurin method. The production of malondialdehyd (MDA) in rat brain mitochondria was tested by thiobarbaturic acid (TBA) assay.

RESULTAV could improve mitochondrial damage induced by azide sodium (NaN3) in PC12 cells. The viability of PC12 cells treated with NaN364 mmol x L(-1) for 4 h decreased by 47.8%, and AV at 1 and 10 mg x L(-1) could respectively increase the viability of NaN3-treated cells by 16.7% (P < 0.05) and 22.3% (P < 0.01). MMP in PC12 cells in AV 1 and 10 mg x L(-1) group was significantly higher than that of NaN3-treated group (P < 0.05). AV also protected the structure and function of mitochondria in rat brain. AV at 10 mg x L(-1) had protective effect on mitochondria function impair induced by NaN3 (P < 0.01). AV 1 and 10 mg x L(-1) markedly inhibited the lipid peroxidation of brain mitochondria induced by Fe2+ -cysteine (P < 0.05, P < 0.01).

CONCLUSIONAV has protective effects on mitochondria of neuronal cells and rat brain.

Aloe ; chemistry ; Animals ; Brain ; drug effects ; metabolism ; Lipid Peroxidation ; drug effects ; Male ; Malondialdehyde ; metabolism ; Mitochondria ; drug effects ; metabolism ; Neurons ; drug effects ; metabolism ; PC12 Cells ; Plant Extracts ; pharmacology ; Plants, Medicinal ; chemistry ; Rats ; Rats, Sprague-Dawley ; Sodium Azide ; pharmacology

OBJECTIVETo investigate effects of total paeony glucosides (TPGs) on the expressions of Toll receptors (TLR4) and interleukin-33 (IL-33) in the brain tissue of D-galactose-induced aging rats. METHODS; Fifty SD rats were randomly divided into 5 groups, i.e., the blank control group, the model group, the high dose TPG group, the middle dose TPG group, and the low dose TPG group, 10 in each group. Equal volume of normal saline was subcutaneously injected to rats in the blank control group, while 10% D-galactose was subcutaneously injected to rats in the rest groups at 0.125 mL/g, once a day for 8 successive weeks to induce the aging rat model. TPG was administered at 300 mg/kg, 150 mg/kg, and 75 mg/kg to rats in the high, middle, and low dose TPG groups while injecting D-galactose from the 5th week of model preparation, once daily for 4 successive weeks. Equal volume of normal saline was administered to rats in the blank control group and the model group, once daily. The capability for learning and memory was detected using Morris water. The mRNA expressions of TLR4 and IL-33 in the brain tissue were detected using ELISA.

RESULTSCompared with the blank control group, the capability for learning and memory decreased in the model group with statistical difference (P < 0.05). Compared with the model group, the capability for learning and memory was obviously improved in all the medicated groups in a dose-dependent manner, showing statistical difference (P < 0.05). Compared with the blank control group, mRNA expressions of TLR4 and IL-33 in the brain tissue obviously increased after medication in the model group, showing statistical difference (P < 0.05). Compared with the model group, mRNA expressions of TLR4 and IL-33 in the brain tissue obviously decreased after medication in all the medicated groups in a dose-dependent manner, showing statistical difference (P < 0.05).

CONCLUSIONTPGs improved D-galactose induced aging rats' capability for learning and memory through regulating changes of TLR4 and IL-33 expressions.

Aging ; drug effects ; Animals ; Brain ; drug effects ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Galactose ; adverse effects ; Interleukins ; metabolism ; Learning ; drug effects ; Male ; Memory ; drug effects ; Paeonia ; chemistry ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4 ; metabolism

OBJECTIVEIn the present study, we investigated the antioxidant and anti-aging effects of Silybum marianum protein hydrolysate (SMPH) in D-galactose-treated mice.

METHODSD-galactose (500 mg/kg body weight) was intraperitoneally injected daily for 7 weeks to accelerate aging, and SMPH (400, 800, 1,200 mg/kg body weight, respectively) was simultaneously administered orally. The antioxidant and anti-aging effects of SMPH in the liver and brain were measured by biochemical assays. Transmission electron microscopy (TEM) was performed to study the ultrastructure of liver mitochondri.

RESULTSSMPH decreased triglyceride and cholesterol levels in the D-galactose-treated mice. It significantly elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC), which were suppressed by D-galactose. Monoamine oxidase (MAO) and malondialdehyde (MDA) levels as well as the concentrations of caspase-3 and 8-OHdG in the liver and brain were significantly reduced by SMPH. Moreover, it increased Bcl-2 levels in the liver and brain. Furthermore, SMPH significantly attenuated D-galactose-induced liver mitochondrial dysfunction by improving the activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase as well as mitochondrial membrane potential (ΔΨm) and fluidity. TEM showed that the degree of liver mitochondrial damage was significantly decreased by SMPH.

CONCLUSIONThe results indicated that SMPH protects against D-galactose-induced accelerated aging in mice through its antioxidant and anti-aging activities.

Aging ; drug effects ; Animals ; Antioxidants ; pharmacology ; Brain ; drug effects ; Caspase 3 ; metabolism ; Galactose ; toxicity ; Gene Expression Regulation, Enzymologic ; drug effects ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Mice ; Milk Thistle ; chemistry ; Mitochondria, Liver ; drug effects ; Oxidative Stress ; drug effects ; Plant Proteins ; chemistry ; pharmacology ; Protective Agents ; pharmacology ; Protein Hydrolysates ; chemistry ; pharmacology ; Superoxide Dismutase ; metabolism