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Objective: To investigate the effects of Erzhi Pill ([Chinese text], EZP) on nerve cell apoptosis in senescence model rats. Methods: The rats model of senescence was established by peritoneal D-galactose injection combined with thymusectomy. Forty SD rats were randomized into four groups, the normal control group, the senescence model group, the EZP treated group, and the vitamins treated group, 10 in each group. The rats were made into senescence model except those in the normal group. In the same time of D-galactose injection, the rats were treated respectively with distilled water, EZP 4.32 g/kg, and vitamins E and C 0.06 g/kg daily for 6 weeks via intragastric infusion. The index of main viscera (as brain, testis, etc.), serum levels of superoxide dismutase (SOD) activity, and total anti-oxidation capacity (T-AOC) were measured after a 6-week treatment. Meanwhile, the cerebral cortex neuronal apoptosis proportion and mitochondrial membrane potential (MMP) were detected by flow cytometry. Results: Both EZP and vitamins E and C treatments showed effects on increasing testis index and serum level of T-AOC, reducing the percentage of neuronal apoptosis in the cerebral cortex, and elevating MMP in the aging rats model. Conclusions: EZP could inhibit the cerebral cortex neuron apoptosis and maintain the mitochondrial function in the senescent process of rats induced by peritoneal D-galactose injection combined with thymusectomy. It also shows antioxidation effect to some extents. [ABSTRACT FROM AUTHOR]

The study explores the application of Tanreqing Injection into brain components in brain diseases. The components of Tanreqing Injection and its existing components in rat cerebrospinal fluid were qualitatively analyzed by liquid chromatography-mass spectrometry(LC-MS). The possible mechanism of action of Tanreqing Injection into brain on brain diseases was predicted by network pharmacological theory. In this study, 17 brain-entry components of Tanreqing Injection were founded, and 222 core targets were obtained from network pharmacological results. The biological processes include 31 items such as negative regulation of apoptotic process, MAPK cascade, Ras protein signal transduction, and 22 items such as PI3 K-Akt signal transduction, MAPK signal transduction and neurotrophic factor signal transduction. Nine brain diseases including stroke, migraine and meningioma were screened out by predicting the effect of Tanreqing Injection on brain components, which provide ideas and directions for further study of a certain encephalopathy and lay a theoretical foundation for further revealing its molecular mechanism.

Stroke is an acute cerebrovascular disease with high morbidity, disability and mortality. The prevention and treatment conditions for stroke is severe all over the world. Antiplatelet aggregation is an effective treatment. Platelet activation factor (PAF) is another important medium in mediating platelet aggregation, which plays an important role in the pathogenesis of stroke. In recent years, PAF receptor antagonists have attracted international attention in the field of stroke prevention and treatment. In this review, we would summarize the classification, mechanism and drug characteristics of PAF receptor antagonists in order to provide the valuable guidance and direction for clinical medicine and research., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

By studying the relationship between syndromes, physique and MMP-9, IL-6 and MTHFR gene polymorphisms in patients with ischemic stroke,The relationship between MMP-9, IL-6 and MTHFR gene polymorphism was analyzed in patients with ischemic stroke.The data were collected by collecting the data of patients with ischemic stroke, and the statistical analysis was carried out. Syndrome：61 cases of ischemic stroke patients with stroke phlegm stasis syndrome in patients with the highest frequency, a total of 30 cases; Physical constitution： phlegm is ischemic stroke patients prone to physical, a total of 20 cases; The analysis of the relationship between constitution and syndrome shows that the patients with qi deficiency constitution tend to show qi deficiency and blood stasis syndrome after onset, The analysis of the relationship between constitution and syndrome shows that the patients with qi deficiency constitution tend to show qi deficiency and blood stasis syndrome after onset, Phlegm constitution and physical condition after the onset of symptoms tend to wind phlegm stasis syndrome; Syndrome and MMP-9, IL-6 relationship：The distribution of MMP-9 and IL-6 in patients with qi and phlegm stasis syndrome and qi deficiency and blood stasis syndrome was significantly different from that in Z test (P<0.05). The level of MMP-9 in patients with qi deficiency and blood stasis syndrome was significantly higher than that in patients with wind phlegm and blood stasis syndrome;The level of IL-6 in patients with phlegm and blood stasis syndrome was significantly higher than that in patients with qi deficiency and blood stasis syndrome. Syndrome, constitution and MTHFR gene polymorphism： among the 61 samples, 34 were heterozygous mutations, 15 were pure and mutated, 12 had no mutation, The mutation rate of this locus was 4.08 times that of patients without mutations.The genotype of MTHFR C677T in patients with phlegm dampness tends to be CT genotype. Wind phlegm stasis syndrome in patients with easy to appear after the TT genotype; Yin deficiency syndrome in patients prone to miscellaneous and mutations, the performance of CT genotype; Analysis of the relationship between syndromes and physique in patients with ischemic stroke,Phlegm and dampness, flat quality patients after the onset of easy to show the wind phlegm stasis syndrome; Qi deficiency after the onset of symptoms in patients with Qi and blood stasis. Suggesting that before the onset of such as for the partial physical conditioning, may be on the prevention of ischemic stroke have a certain effect; Analysis of the relationship between syndromes and MMP-9 and IL-6 in patients with ischemic stroke, Wind phlegm stasis syndrome and IL-6 levels are related, Qi deficiency and blood stasis syndrome and MMP-9 levels are related. Analysis of the relationship between syndromes and MTHFR gene polymorphism in patients with ischemic stroke, TT genotype after the onset of symptoms prone to wind phlegm stasis syndrome, CT genotype patients after the onset of easy manifestations of Yin deficiency wind syndrome; Analysis of the relationship between physique and MTHFR gene polymorphism in patients with ischemic stroke, CT genotype is easy to show phlegm.For more in-depth understanding of pathogenesis of ischemic stroke to provide the basis, For the clinical treatment and prevention to provide intervention strategies., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

This study aimed to analyze the analgesic effect and related central mechanisms of CQ prescription on cancer invasion induced mirror image pain (CIIMIP)in model mice.In the study, male BALB/c mice were randomly divided into normal group, operation control group (injected with 0.2 mL inactivated S180 sarcoma cell sap), model group (injected with 0.2 mL S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and CQ prescription low dose group (intraperitoneally injected with CQ prescription 100 mg•kg⁻¹ on the basis of model mice), CQ prescription middle dose group (intraperitoneally injected with CQ prescription 150 mg•kg⁻¹ on the basis of model mice), and CQ prescription high dose group (intraperitoneally injected with CQ prescription 200 mg•kg⁻¹ on the basis of model mice). Mechanical withdraw threshold (MWT) of the mirror image lateral hind paws were evaluated by Von Frey hairs before modeling and after surgery. The levels of glutamate (Glu), gamma aminobutyric acid (GABA), glycine (Gly), and taurine (Tau) in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector (HPLC-FLD); AimPlex detection technology with multiple factors was used to detect the levels of regulated on activation in normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP-3) in the L3-L5 spinal cord. Then we observed the influence of GABAa receptor antagonist (Bicuculline) on analgesic effect of CQ prescription.The results indicated that CQ prescription could remarkably increase MWT of model mice(P<0.01, P<0.05), decrease the level of Glu(P<0.01, P<0.05), improve the levels of GABA, Gly, Tau(P<0.01, P<0.05), lower the ratio of Glu/GABA(P<0.01, P<0.05), and reduce the levels of RANTES, MCP-3(P<0.05) in the L3-L5 spinal cord, and GABAa receptor antagonist significantly blocked the analgesic effect of CQ prescription at two time points(P<0.05).This study showed that CQ prescription had significant analgesic effect on CIIMIP model mice, and its mechanism was associated with regulating the balance between excitability amino acid(EAA) and inhibitory amino acid (IAA) transmitters in central nervous system, partially activating GABAa receptor, and reducing the release of RANTES and MCP-3 in the spinal cord., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To observe the effect of synchronous perfusion of specific respiratory chain complex IV inhibitor sodium azide (NaN3) in brain on rat ventromedial prefrontal cortex (mPFC) and acetylcholine (ACh) and choline (Ch) contents in hippocampal extra-cellular fluid, and establish the AD rat model induced by mitochondrial acute injury., Method: The synchronous dual-probe dual-channel brain microdialysis sampling technology was applied to synchronously perfuse modified Ringer's solution containing NaN3 (50 micro mol L-1) and neostigmine (2 micro mol L-1) into mPFC and hippocampus of conscious, freely moving normal rats, and continuously collect dialysates from different encephalic areas. Dynamic contents of ACh and Ch were determined by high performance liquid chromatography-post-column immobilized enzyme reactor-electrochemical process., Result: ACh and Ch contents in mPFC extracellular fluid of normal rats were higher than that in hippocampus. During the process of perfusion, NaN3 could significantly reduce ACh in mPFC/hippocampal extra-cellular fluid, but remarkably increase Ch, and constantly inhibit the recovery of ACh and Ch contents in mPFC/hippocampus., Conclusion: The synchronous perfusion of NaN3in rat mPFC and hippocampus can injure functions of the cholinergic nerve projection area, and cause the acute AD model with ACh and Ch metabolic disorders. This model can be used in pathogenetic and pharmacological studies.

Objective: To observe the analgesic effect of CQM on photochemically-induced prosopalgia model rats, and discuss its impact on the exciting amino acid neurotransmitter-glutamate (Glu)., Method: Male SD rats were randomly divided into the sham operation group and the prosopalgia group. And the latter was subdivided into the model group, the gabapentin group (100 mg kg(-1)), and the CQM low-dose (35 mg x kg(-1)) and CQM high-dose (70 mg x kg(-1)) groups. The mechanical allodynia test was adopted to evaluate the pain behavior of rats, and reflect the efficacy with the mechanical withdrawal thresholds. The rat striatum extra-cellular fluid was collected by brain micro-dialysis. The Glu level of samples was measured by high performance liquid chromatography-fluorescene detector (HPLC-FLD)., Result: Compared to the control group, the threshold of the mechanical allodynia of the IoN injury group was decreased significantly (P < 0.05), and the concentration of Glu was increased dramatically (P < 0.05). Compared to the model group, the mechanical allodynia of photochemically-induced prosopalgia model rats increased significantly (P < 0.01), with a notable increase in brain Glu concentration (P < 0.05). Compared with the model group, all of mechanical withdrawal thresholds increased. Among them, the CQM high-dose group showed a remarkably growth at three time points (P < 0.05), with the maximum up to (23 +/- 7.3) g. And the gabapentin group showed a remarkably growth at two time points (P < 0.05), with the maximum up to (20.5 +/- 9.2) g. All of the drug groups showed significantly lower Glu concentrations in rat brains than the model group (P < 0.05)., Conclusion: CQM can ease the mechanical allodynia of photochemically-induced prosopalgia model rats. Its analgesic effect may be related to the decrease of Glu concentrations in striatum extra-cellular fluid.

Objective: To observe the analgesic effect of sinomenine on the neuropathic pain rat model induced by SSNI, and discuss its impact on monoamine neurotransmitters in striatal extracellular fluid., Method: Male SD rats were randomly divided into the sham operation group, the SSNI model group, the gabapentin group (100 mg x kg(-1)), the sinomenine high dose group (40 mg x kg(-1)) and the sinomenine low dose group (20 mg x kg(-1)). Mechanical hyperalgesia and cold pain sensitivity were evaluated by Von Frey hairs and cold spray. Striatum was sampled by microdialysis. High performance liquid chromatography-electrochemical detector (HPLC-ECD) were used to detect the content of such neurotransmitters as monoamine neurotransmitters noradrenaline (NE), dopamine (DA), 5-hydroxy tryptamine (5-HT) and their metabolites dihydroxyphenylacetic phenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA)., Result: SSNI model rats showed significant improvement in mechanical withdrawal threshold and cold pain sensitivity, significant decrease in intracerebral NE and notable increase in DA, 5-HT and their metabolites. Compared with the model group, the sinomenine high dose group showed significant increase in mechanical withdrawal threshold at 60, 90, 180 and 240 min after abdominal administration (P < 0.01), significant decrease in cold pain sensitivity score during 30-240 min (P < 0.05). Sinomenine can significantly up-regulated NE content in striatal extracellular fluid during 45-135 min (P < 0.05), remarkably reduce DA content and DOPAC at 45, 75 and 135 min (P < 0.05), 5-HT content during 45-135 min, DOPAC during 75-165 min (P < 0.05), and 5-HIAA during 45-135 min (P < 0.05)., Conclusion: Sinomenine has the intervention effect on neuropathic pain in SSNI model rats. Its mechanism may be related to disorder of monoamine neurotransmitters in striatal extracellular fluid.

Parkinson cents disease (PD) is a common extrapyramidal disease, of which the cardinal symptoms are hypokinesia, muscular rigidity, and tremor. The main pathological characteristics of this disease are loss of dopamine neurons in substantia nigra pars compacta, and residual neurons often contain Lewy bodies. The PD pathogenesis is still not well known, while it is generally recognized that age and environmental factors participate in it. In recent years, genetic research on PD has made considerable progresses that genetic factors play important roles on the pathogenesis of PD, and multiple PD related genes, such as SNCA, LRRK2, PINK1, parkin, UCHL1, and DJ1, have been identified. This article summarizes recent progresses on these genes to provide reference for PD study.

Objective: To observe the effects of tetramethylpyrazine (TMP) on brain oxidative damage induced by intracerebral perfusion of levodopa (L-DOPA) in rats with Parkinson's disease (PD)., Methods: PD model rats were induced by intracerebral injection of 6-hydroxyl dopamine (6-OHDA) and perfused in brain with L-DOPA using microdialysis technique. Changes in levels of 2,3-dihydroxy benzyl acid (2.3-DHBA) and 2,5-dihydroxy benzyl acid (2,5-DHBA) in striatum of rats, formed by extracellular hydroxyl radical from salicylic acid capturing, were dynamically observed at various time points by HPLC-ED., Results: After treatment with L-DOPA, 2,3-DHBA and 2,5-DHBA in the model group showed significantly higher levels at 6 and 7 time points as compared with those in the sham-operated group at the corresponding time points (P <0.05 or P< 0.01), while these abnormal elevations were significantly inhibited in the TMP treated groups, either in large or small dose (P<0.05 or P<0.01)., Conclusion: TMP could reduce the L-DOPA induced brain oxidative damage in PD rats.

Objective: To investigate the protection mechanism of prepared Polygonum multiflorum (PPMT) in rat brain with sodium azide (NaN3) perfusion., Method: Rats were divided into six groups: control, model, PPMT, Duxil and PPMT + Duxil groups. The intracerebral microdialysis and high performance liquid chromatography-post column Immobilized enzyme reactor-electrochemical detection were used to continuously measure extracellular acetylcholine (ACh) and choline (Ch) levels in striatum of freely moving awake rats., Result: The extracellular Ach, Ch levels of striatum stayed stable in the control group during the whole observing period, but the ACh levels in the model group were lower significant than that in the control group. The Ach levels of three drug groups were respectively higher significant than that of model group at some time points. While the extracellular Ch level in striatum of the model group increased singnificantly compared with the control group. The Ch levels of the three drug groups were lower significant than that of the model group respectively at certain time points. The effects of PPMT were similar with that of Duxil., Conclusion: The prepared P. multiflorum can improve the impaired cholinergic nerve function to exert the effects of brain protection by elevating extracellular Ach level and improving uptake of extracellular Ch. It may provide the experimental evidence to support the idea that P. multiflorum could be brain protective drug to treat retrogressive disease such as dementia.

Objective: To investigate the effect and mechanism of prepared Radix Polygoni Multiflori (RPM) on the elevation of extracellular hydroxyl radical in striatum of rats induced by intracerebral perfusion of 6-hydroxy dopamine (6-OHDA)., Methods: Cerebral microdialysis was used to establish the model. Hydroxyl radical was captured by salicylic acid, and 2,3-dihydroxy benzyl acid (2,3-DHBA) and 2,5-dihydroxy benzyl acid (2,5-DHBA) formed by hydroxyl radical in vital brain were measured by high performance liquid chromatography-electrochemical detector (HPLC-ED)., Results: After perfusion of 6-OHDA in brain of rats, the levels of 2,3-DHBA and 2,5-DHBA in the model group increased rapidly. The former was higher during the whole course of observation (P<0.01), while the latter was higher at most time points than that in the control group (P<0.05 or P<0.01). The level of 2,3-DHBA in the RPM group was lower than that in the model group at 5 time points (P < 0.05, P < 0. 01)., Conclusion: RPM could inhibit the elevating of extracellular hydroxyl radical in striatum of rats induced by intracerebral perfusion of 6-OHDA, indicating one of the brain protective mechanisms of RPM may be related to its anti-oxidation effect.

This paper reviews the brain protective effect and mechanism of Polygonum multiflorum (PM), its extracts and active component, tetrahydroxystilbene-glucoside (2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside) published in recent decade. They have major effects as calcium channel antagonists, antioxidant, cholinomimetic drugs and cholinesterase inhibitors, as well as actions in regulating cell apoptosis and prolonging the ageing. The brain protective mechanism of PM is multi-target, multi-link and multi-way. Therefore, PM has great applicative value in prevention and treatment of senile neuropathies, such as Alzheimer's disease, Parkinson's disease and vascular dementia, etc.

Objective: To investigate the effect of Tianma Gouteng recipe (TGR) on interfering left ventricular (LV) and aortic hypertrophy and tissue angiotensin II (Ang II) in rats with renovascular hypertension., Method: The animal model of renovascular hypertension was used in this experiment. Hypertensive rats were randomly allocated into model group, Enalapril group and TGR group, and the drugs were used for 6 weeks continuously. During this period, the blood pressure of rats was measured every two weeks. After rats were sacrificed, the wet weight, tissue Ang II level of LV and aorta, and the cardiac index were measured., Result: One week after renovascular stenosis, the systolic blood pressure (SPS) of model group was increased by 37.4 mmHg, and 7 weeks after stenosis, the LV and aortic hypertrophy was obvious increased, meanwhile, tissue Ang II of LV and aorta was raised markedly (P < 0.01). Contrasting with the model group, blood pressure was reduced and the morphological index was improved in Enalapril group respectively (P < 0.05 or P < 0.01); the wet weight of LV and aorta were reduced, the morphological index was improved, the rise of Ang II in tissue was suppressed, in TGR group significantly., Conclusion: TGR can attenuate myocardial and aorta hypertrophy induced by renovascular hypertension, and suppress the rise of Ang II in tissue significantly. This suggests that TGR has the effects on interfering LV and aortic hypertrophy by an independent-antihypertensive way.

Objective: To investigate the effects of Tianzhi Keli (TZ) on acetylcholine (ACh) and catecholamine levels in striatum of rats with neuromitochondrial impairment, and try to find out the neuroprotective mechanism of TZ., Method: The microdialysis and high performance liquid chromatography (HPLC)-post column Immobilized enzyme reactor (IMER)-electrochemical detection (ED) were used to establish a model of mitochondrial energy metabolism impairment which induced by perfusion with sodium azide (NaN3), and measure continuously the effects of TZ on extracellular ACh, choline (Ch) and catecholamine of model rats., Result: After perfusion with NaN3, ACh, noradrenalin (NE), adrenaline (E), dopamine (DA), 3,4-Dihydroxyphenyl-aletic (DOPAC), and homovanillic acid (HVA) levels were decreased obviously (P < 0.05-0.01), while Ch level was increased distinctly (P < 0.01). Transmitters levels were recovered individually after stop the perfusion with NaN3. TZ can postpone the decrease of ACh and advance the recover of Ch. The effect of TZ coupled with duxil on increasing ACh level is more obviously than effect of TZ or duxil. TZ is also showing a tendency to postpone the decrease of catecholamine and advance its recovery. TZ coupled with duxil can advance the recovery of DOPAC and adjust the metabolic abnormity positively., Conclusion: TZ has effect on protecting impairment of choline neurosystem, which induced by damage of mitochondrion and abnormity of energy metabolism; coupled with duxil have synergistic action. TZ also has tendency to protect the impairment of epinephrine and dopamine neurosystem.

Objective: To observe the effects of Tianma Gouteng Fang (TGF) on the transmitter amino acids in the hippocampus extracellular liquids in freely moving rats subjected to incomplete brain ischemia., Method: Hippocampus extracellular liquids was collected continuously by the microdialysis sampling technology in freely moving rats during pre-ischemia, incomplete ischemia and reperfusion periods induced by the occlusion and loose of both common carotid arteries. Each dialysate sample was assayed for GABA, Tau, Glu, Cys and Arg with HPLC-electrochemical detector., Result: TGF increased the concentrations of GABA and Tau in the extracellular liquids of rat hippocampus. Compared with the model group, the concentration of Glu in the middle and large dosage groups of TGF, during the 120 min of ischemia, reduced by 38.64% and 31.35%, Tau increased by 13.99% and 12.86%, GABA advanced 25.89% and 33.99%, Cys decreased by 40.93% and 42.08%, Arg raised to 116.95% and 108.96%, respectively. After 120 min of reperfusion, the concentration of Glu decreased by 14.55% and 11.48%, Tau increased by 16.13% and 14.03%, GABA increased by 24.41% and 26.22%, respectively., Conclusion: TGF can increase the concentration of inhibitory amino acids in hippocampus extracellular liquids of rats and inhibit the excessive release of excitatory amino acids and raise the concentration of the inhibitory amino acids and Arg during the ischemia-reperfusion periods. Therefore, TGF can play the neuroprotective role.

The effects of Gastrodia elata on preventing decrepitude and advancing memory are closely associated with its neuroprotective activity. Previous researches proved that G. elata, its active components and preparations played a neuroprotective role by affecting the excitotoxicity, nitric monoxide (NO) system, neuroglia, biomembrane, oxidative neurotoxicity, apoptosis et al. Recent researches also suggest that reducing energy metabolism impairment, anti-inflammatory and immune modulating function may be new research targets of neuroprotective mechanism of G. elata.