δ阿片受体激动剂对大鼠全脑缺血再灌注损伤神经保护作用的研究

如今心肺脑复苏（cardiopulmonary cerebral resuscitation，CPCR）一直是急诊医学研究的重要内容。心肺复苏的目的在于脑复苏，脑复苏成功与否决定整个抢救的成败。因此目前心肺脑复苏的研究比较集中在以脑复苏为重点的后期复苏和高级生命支持。由于脑细胞对缺氧十分敏感，循环停止和6min脑组织即可出现不可逆性损害。脑损害是心肺脑复苏后患者致残的主要原因，因而，对这些患者的救治就显得异常重要，包括早期正确实施心肺复苏及后期综合性的脑保护治疗。

自适应多保真数据融合的神经网络模型

数据驱动的深度学习建模在力学、材料等不同学科中得到了较多应用。深度学习建模的精度依赖大量高保真数据。在实际应用中,高保真数据往往是少量且昂贵的,而低保真数据却是成本低廉且数量较多的。当高保真数据量过少时,深度学习建模精度较低。近期发展的多保真深度神经网络,通过融合不同保真度的数据,在高保真数据较少时,依然保持了较高的建模精度。然而,已有的多保真深度神经网络模型的精度较为依赖针对模型参数的正则化调节。当添加的正则化过强时,网络对非线性关联式的拟合能力不足;当添加的正则化强度不够时,在学习多保真数据间的线性关联关系时又会出现过拟合现象。两者都会严重影响模型的预测精度。在缺乏高保真验证数据集时,较难得到最优的正则化系数。为此,通过改进已有多保真网络模型的损失函数,引入一个与线性关联式相关的参数,提出了自适应多保真数据融合的神经网络模型。该模型能根据给定数据自适应地拟合不同保真度数据间的线性或非线性关系,对正则化依赖较小,从而提高了建模的鲁棒性。在多个标准测试案例及实际应用的翼型气动参数的预测中,该模型均能表现出较高的精度和稳定性。

保留盆腔自主神经的直肠癌术后性功能分析

目的 :探讨直肠癌传统手术与保留盆腔自主神经的手术对性功能影响的差异。方法 :回顾性分析 2 0 0 0年 4月至 2 0 0 1年 12月收治 4 8例直肠癌的手术方式和随访资料。结果 :传统手术与保留盆腔自主神经的手术切除直肠癌患者术前后在性欲、阴茎勃起、性高潮、射精的比较上有显著性差异。结论 :直肠癌保留盆腔自主神经的手术对性功能的保护明显优于传统手术方式 ,值得在临床上推荐。

R-apomorphine protects against 6-hydroxydopamine-induced nigrostriatal damage in rat

Objective The aim of the present study was not only to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra （SN） and ventral tegmental area （VTA） after injection of 6-hydroxydopamine （6-OHDA） into the striatum, but also to use this 6-OHDA model of Parkinson＇s disease to explore the possible neuroprotective effect of R-apomorphine （R-APt）. Methods The partial lesion was obtained by intrastriatal administration of 6-OHDA. R- APt administration （10 mg/kg, s.c.） started 15 min prior to lesioning and continued daily for another 22 days post surgery. Testing was carried out 5 weeks after lesioning. We investigated the histology and associated behavior and neurochemical changes. Structural and functional deficits were quantified by tyrosine hydroxylase （TH） / Nissl-staining cell number counting, striatal dopamine （DA） content determination and amphetamine-induced rotation analysis. Results R-APt- treatment attenuated the amphetamine-induced ipsiversive rotation 5 weeks after the lesion induction. R-APt administra- tion for 22 days significantly reduced the size of the lesion at the level of the SN from 50% （control group） to 69%. Moreover, the cell shape resembled that observed in the intact animals. R-APt treatment significantly increased the number of cells in both the lesion and the intact sides of VTA by 60%, suggesting selective neurotrophic effect of R-APt in this area. Finally, R-APt-treatment significantly attenuated the 6-OHDA-induced striatal DA depletion and normalized dihydroxyphenylacetic acid （DOPAC）/DA ratios. Conclusion We conclude that R-APt has neuroprotective and pos- sible neurotrophic effect on a striatal lesion with 6-OHDA, suggesting that this drug may have rescuing properties in patients with early stage Parkinson＇s disease. These effects are more pronounced in VTA and enhance with duration of treatment.

Neuroprotective Effects of Bushen Decoction Against Glutamate-Induced Neurotoxicity in PC12 Cells

Aim The enhanced effect of Bushen (Kidney-tonifying) decoction (BS) oncultured PC12 cell proliferation and its antagonistic action on neurotoxicity induced by glutamatewere investigated by serum pharmacological method of the Chinese material medica (CMM) in vitro.Methods The effect of BS on cultured PC12 cell activity and its antagonistic action on neurotoxicityinduced by glutamate was observed by MTT method. Flow cytometry and fluorescence microscopetechniques were employed to observe the antagonistic effect of BS on early period apoptosis of PC12cells induced by glutamate. Results The serum with BS was able to enhance activity of PC12 cells andexert antagonistic effect on glutamate-induced neurotoxicity. Meanwhile, these beneficial effectsproduced by BS were found to be the strongest in 20% concentration of in serum BS. Moreover, it caninhibit apoptosis of PC12 cells induced by glutamate , which occurs in the early period. ConclusionBS may exert a potential neuroprotective effect.

Research on development of urban taxi supply based on influence factors classification

In order to determine the regulations of the development of taxi supply under entry regulations in Chinese cities, an improved neural network model is applied to find the particular years when the government artificially puts new taxis into the market, and then extract the political influence from the taxi supply. The model is also utilized to study the relationships between the adjusted taxi supply and non-policy factors. A case study of Nanjing city is conducted. The results show that 2001 and 2007 are the particular years that the Nanjing government artificially put new taxis into its taxi market, which is in accordance with the five-year plan of China and the local development plans. The results also show that the improved neural network model has a good performance in expositing the evolution of adjusted taxi supply related to non-policy factors.

Neuroprotective Effects of Modafinil on MPTP Mouse Model of Parkinson′s Disease

Aim To observe the neuroprotective effects of modafinil on the Parkinson'sdisease ( PD ) model induced by 1-methyl-4-phenyl-1, 2,3, 6-tetrahydropyridine (MPTP ). Methods Themodel of PD was induced by intraperitoneal injection of MPTP into C57BL/6J mice for 4 d. Modafinil(ip, 50 or 100 mg·kg^(-1)·d^(-1)) was administered following MPTP for 4 d and for another 10 dconsecatirely. The effects of modafinil on the locomotor activity, and the incubation, maintenanceperiod and grade of the tremor, the duration of the climbing rod of mouse, and the distribution ofpositive cells of ty-rosine hydroxylase (TH) and Nissl bodies in the striatum and substantia nigra(SN) were observed. The contents of dopam-ine (DA) , noradrenaline (NA) and 5-hydroxytryptamine(5-HT) in the striatum were determined. Results Modafinil (50 and 100 mg·kg^(-1)) significantlyprevented the locomotor, the tremor and climbing rod defect behavior in a dose-dependent manner (P <0.05 and P < 0.01, n = 10), prevented the decrease in the number of TH-positive cells and Nisslbodies (P<0.05, n=10), and reduced the decrease of DA, NA, and 5-HT in the striatum (P < 0.05, n =10) induced by MPTP. Conclusion Modafinil improves the behavioral deficits and prevents themonoaminergic neuron lesion in seriously impaired MPTP mouse model.

Effect of NGF on c-fos mRNA Expression in Spinal Neuron after Spinal Cord Injury

Objective: To expound the mechanism of nerve growth factor (NGF) to protectspinal cord against injury. Methods: Forty-five rats with 10 g X 2. 5 cm impact T_8 spinal cordinjury (SCI) were divided into 3 groups. The experimental animals received 60 g NGF purified frombovine seminal plasma instantly, 1, 2, 4 h after in jury and an equal volume of normal saline wasgiven to the control group at the same time. The c-fos mRNA levels were detected by in situhybridization. Results: The results showed no evident c-fos expression in normal control group. Thec-fos expression increased markedly in damaged neurons. The peak value of c-fos mRNA arose at 1 h,and c-fos levels in NGF group reduced evidently. Conclusion: NGF could inhibit c-fos expression. Itmay serve as one of the action mechanisms of NGF to protect spinal cord against injury.

Lipopolysaccharide preconditioning induces protection against lipopolysac-charide -induced neurotoxicity in organotypic midbrain slice culture

Objective To identify the protective effect of lipopolysaccharide （LPS） preconditioning against LPS-induced inflammatory damage in dopaminergic neurons of midbrain slice culture and the possible mechanisms. Methods After cultured in vitro for 14 d, the rat organotypic midbrain slices were pretreated with different concentrations （0, 1, 3, 6 or 10 ng/mL） of LPS for 24 h followed by treatment with 100 ng/mL LPS for 72 h. The whole slice viability was detelmined by measurement of the activity of lactic acid dehydrogenase （LDH）. Tyrosine hydroxylase-immunoreactive （TH-IR） neurons and CD 1 1 b/c equivalent-immunoreactive （OX-42-IR） microglia in the slices were observed by immunohistochemical method, and tumor necrosis factor-α （TNF-α levels in the culture media were detected by enzymelinked immunosorbent assays （ELISA）. Results In the slices treated with 100 ng/mL LPS for 72 h, the number of TH-IR neurons reduced from 191± 12 in the control slices to 46±4, and the LDH activity elevated obviously （P 〈 0.01）, along with remarkably increased number of OX-42-IR cells and production of TNF-α （P 〈 0.01）. Preconditioning with 3 or 6 ng/mL LPS attenuated neuron loss （the number of TH-IR neurons increased to 126± 12 and 180± 13, respectively） and markedly reduced LDH levels （P 〈 0.05）, accompanied by significant decreases of OX-42-IR microglia activation and TNF-α production （P 〈 0.05）. Conclusion Low-dose LPS preconditioning could protect dopaminergic neurons against inflammatory damage in rat midbrain slice culture, and inhibition of microglial activation and reduction of the proinflammatory factor TNF-α production may contribute to this protective effect. Further understanding the underlying mechanism of LPS preconditioning may open a new window for treatment of Parkinson＇s disease.

Neuroprotective effects of receptor imidazoline 2 and its endogenous ligand agmatine

Receptor imidazoline 2 （I2） is one of the imidazoline receptors with high affinity for [^3H]-idazoxan. Receptor I2, being classified into I2A and I28 subtypes, is mainly localized to the outer membrane of mitochondria in liver, kidney and brain. Receptor I2, displaying high similarity of sequence with monoamine oxidase-B （MAO-B）, is structurally related to MAO-B, but the I2 imidazoline binding site （IEBS） with ligand is distinct from the catalytic site of MAO-B. Agmatine is the endogenous ligand of receptor I2. Accumulating evidence have revealed that the activation of receptors I2 may produce neuroprotective effects by increasing expression of glial fibriUary acidic protein （GFAP） in astrocytes, inhibiting activity of MAO, reducing calcium overload in cells. Agmatine exerts neuroprotection against ischemia-hypoxia, injury, glutamateinduced neurotoxicity by activating imidazoline receptors, blocking N-methyl-D-aspartate （NMDA） receptor, inhibiting all isoforms of nitric oxide synthase （NOS）, and selectively blocking the voltage-gated calcium channels （VGCC）. It would be expected that agmatine is one of the potential neuroprotective agents.

Neuroprotective action of Ginkgo biloba on the enteric nervous system of diabetic rats

AIM: To investigate the effect of Ginkgo biloba extract on the enteric neurons in the small intestine of diabetic rats. METHODS: Fifteen Wistar rats were divided into three groups: control group (C), diabetic group (D) and diabetic-treated (DT) daily with EGb 761 extract (50 mg/kg body weight) for 120 d. The enteric neurons were identified by the myosin-V immunohistochemical technique. The neuronal density and the cell body area were also analyzed. RESULTS: There was a significant decrease in the neuronal population (myenteric plexus P = 0.0351; submucous plexus P = 0.0217) in both plexuses of the jejunum in group D when compared to group C. With regard to the ileum, there was a significant decrease (P = 0.0117) only in the myenteric plexus. The DT group showed preservation of the neuronal population in the jejunum submucous plexus and in the myenteric plexus in the ileum. The cell body area in group D increased significantly (P = 0.0001) in the myenteric plexus of both segments studied as well as in the ileum submucosal plexus, when compared to C. The treatment reduced (P = 0.0001) the cell body area of the submucosal neurons of both segments and the jejunum myenteric neurons. CONCLUSION: The purified Ginkgo biloba extract has a neuroprotective effect on the jejunum submucous plexus and the myenteric plexus of the ileum of diabetic rats.

Effect of lead on ERK activity and the protective function of bFGF in rat primary culture astroglia

Objective： To observe the effects of lead on levels ofphosphorylated extracellular signal regulated kinase （p-ERK） in the cytoplasm of primary cultures of rat astroglial cells and the possible protective effect of basic fibroblast growth factor （bFGF） on lead-induced effects. Methods： The primary astroglia cells from 1-6 d old Wistar rats were cultured. The cells pretreated with the MEK1 （mitogen-activated protein kinase kinase 1） inhibitor PD98059 and bFGF, respectively, were exposed to Pb acetate of different concentrations for different times. Western blotting and reverse transcription polymerase chain reaction （RT-PCR） methods were used to detect the protein and mRNA expressions of ERK. Results： mRNA expression for ERK peaked 15 min after initiation of lead exposure （P〈0.05） and protein expression of p-ERK peaked at 30 min （P〈0.05）. ERK mRNA levels and p-ERK protein levels returned to baseline after 60 and 120 min of lead exposure, respectively （P〉0.05）. The increase in p-ERK levels in lead-treated cells could be inhibited by PD098059. Activation of ERK in the cells by lead was prevented by pretreatment with bFGF. Total ERK protein levels did not change under the same experimental conditions （P〉0.05）. Conclusion： Low-level lead exposure resulted in transient activation of ERK through the MEK pathway, which then returned to basal levels in the continued presence of lead. Exogenous bFGF protected ERK signaling components in astroglia from lead poisoning.

INTRANASAL DELIVERY OF NERVE GROWTH FACTOR TO PROTECT THE CENTRAL NERVOUS SYSTEM AGAINST ACUTE CEREBRAL INFARCTION

Objective To confirmed reliability and feasibility of intranasal nerve growth factor (NGF) bypassing the blood-brain barrier and its potential neuroprotective effects on acute cerebral ischemia. Methods (1) To assay NGF concentrations in different brain regions after middle cerebral artery occlusion (MCAO).Rats were randomly divided into intranasal (IN) NGF, intravenous (IV) NGF, and untreated group (n= 4). The concentra-tions of NGF of different brain regions in the three groups after MCAO were measured by ELISA. (2) To observe neuro-protective action of NGF on focal cerebral ischemic damage. Rats were randomly assigned to 4 groups: IN vehicle, IN NGF, IV vehicle, IV NGF (n= 8). Treatment was initiated 30 minutes after onset of MCAO and given again 24 hours later. Three neurologic behavioral tests were performed 24 and 48 hours following onset of MCAO. Corrected infarct volumes were determined 48 hours after onset of MCAO. Results The olfactory bulb in IN NGF group obtained the highest concentration (3252 pg/g) of NGF among all regions, followed by the hippocampus. The NGF concentrations in the olfactory bulb and hippocampus in IN NGF group were markedly higher than that in IV NGF and control groups. The infarct volume in IN NGF group was markedly reduced by 38.8% compared with IN vehicle group. IN NGF group vestibulum function markedly improved compared with IN vehicle group at 24 and 48 hours after onset of MCAO (P 24 h = 0.02 and P 48 h = 0.04, respectively). Conclusion Intranasal NGF could pass through the blood-brain barrier, reach the central nervous system, reduce infarct volume, and improve neurologic function in rats following MCAO. Intranasal delivery of NGF may be a promising treat-ment for stroke.

Effects of vagus nerve preservation and vagotomy on peptide YY and body weight after subtotal gastrectomy

AIM:To investigate the relationship between the function of vagus nerve and peptide YY 3-36 and ghrelin levels after subtotal gastrectomy.METHODS:We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer.All surgeries were performed by a single skilled surgeon.We measured peptide YY 3-36,ghrelin,leptin,insulin,growth hormone levels,and body weight immediately before and one month after surgery.RESULTS:Vagus nerve preservation group showed less body weight loss and less increase of peptide YY 3-36 compared with vagotomy group(-5.56 ± 2.24 kg vs-7.85 ± 1.57 kg,P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL,P = 0.021,respectively).Moreover,patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY 3-36 level,typically less than 20% [6(66.7%) vs 0(0.0%),P = 0.011,odd ratio = 3.333,95% confidence interval(1.293,8.591)].CONCLUSION:Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy,and this phenomenon may be related to the suppressed activity of peptide YY 3-36.

Gastro-protective action of lafutidine mediated by capsaicin-sensitive afferent neurons without interaction with TRPV1 and involvement of endogenous prostaglandins

AIM： Lafutidine, a histamine H2 receptor antagonist, exhibits gastro-protective action mediated by capsaicinsensitive afferent neurons （CSN）. We compared the effect between lafutidine and capsaicin, with respect to the interaction with endogenous prostaglandins （PG）, nitric oxide （NO） and the afferent neurons, including transient receptor potential vanilloid subtype 1 （TRPV1）. METHODS： Male SD rats and C57BL/6 mice, both wildtype and prostacyclin IP receptor knockout animals, were used after 18 h of fasting. Gastric lesions were induced by the po administration of HCl/ethanol （60% in 150 mmol/L HCl） in a volume of 1 mL for rats or 0.3 mL for mice. RESULTS： Both lafutidine and capsaicin （1-10 mg/kg, po） afforded dose-dependent protection against HCI/ ethanol in rats and mice. The effects were attenuated by both the ablation of CSN and pretreatment with NG-nitro- L-arginine methyl ester, yet only the effect of capsaicin was mitigated by prior administration of capsazepine, the TRPV1 antagonist, as well as indomethacin. Lafutidine protected the stomach against HCl/ethanol in IP receptor knockout mice, similar to wild-type animals, while capsaicin failed to afford protection in the animals lacking IP receptors. Neither of these agents affected the mucosal PGE2 or 6-keto PGF1α contents in rat stomachs. Capsaicin evoked an increase in [Ca^2＋]i in rat TRPV1-transfected HEK293 cells while lafutidine did not. CONCLUSION： These results suggest that although both lafutidine and capsaicin exhibit gastro-protective action mediated by CSN, the mode of their effects differs regarding the dependency on endogenous PGs/IP receptors and TRPV1. It is assumed that lafutidine interacts with CSN at yet unidentified sites other than TRPV1.

Using the endocannabinoid system as a neuroprotective strategy in perinatal hypoxic-ischemic brain injury

One of the most important causes of brain injury in the neonatal period is a perinatal hypoxicischemic event.This devastating condition can lead to long-term neurological deficits or even death.After hypoxic-ischemic brain injury,a variety of specific cellular mechanisms are set in motion,triggering cell damage and finally producing cell death.Effective therapeutic treatments against this phenomenon are still unavailable because of complex molecular mechanisms underlying hypoxic-ischemic brain injury.After a thorough understanding of the mechanism underlying neural plasticity following hypoxic-ischemic brain injury,various neuroprotective therapies have been developed for alleviating brain injury and improving long-term outcomes.Among them,the endocannabinoid system emerges as a natural system of neuroprotection.The endocannabinoid system modulates a wide range of physiological processes in mammals and has demonstrated neuroprotective effects in different paradigms of acute brain injury,acting as a natural neuroprotectant.The aim of this review is to study the use of different therapies to induce long-term therapeutic effects after hypoxic-ischemic brain injury,and analyze the important role of the endocannabinoid system as a new neuroprotective strategy against perinatal hypoxic-ischemic brain injury.

Protective effects of Zuogui Jiangtang Jieyu Formula on hippocampal neurons in rats of diabetes complicated with depression via the TRP/KYN metabolic pathway

Objective To explore the protective effects and mechanism of Zuogui Jiangtang Jieyu Formula(左归降糖解郁方,ZGJTJYF)on hippocampal neurons in rats of diabetes complicated with depression(DD)via the TRP/KYN metabolic pathway.Methods(i)In vivo experiments:60 specified pathogen free(SPF)grade male Sprague-Dawley(SD)rats were randomly divided into six groups with 10 rats in each groups:control,DD model,positive(1.8 mg/kg fluoxetine+0.18 g/kg metformin),high-dose ZGJTJYF(ZGJTJYFH,40.500 g/kg ZGJTJYF),middle-dose ZGJTJYF(ZGJTJYF-M,20.250 g/kg ZGJTJYF),and lowdose ZGJTJYF(ZGJTJYF-L,10.125 g/kg ZGJTJYF)groups.Except for the control group,other groups were established DD model by high-fat emulsion intake with single tail vein streptozotocin(STZ)and four weeks of chronic unpredictable mild stress(CUMS).All drug administration groups were treated by gavage during CUMS modeling,and the control and model groups were given equal amount of distilled water.After four weeks,the serum levels of blood glucose and glycosylated hemoglobin were measured to determine the hypoglycemic effect of ZGJTJYF.Moreover,the open field test and Morris water maze test were performed to evaluate the antidepressant effect of ZGJTJYF.Changes in 5-hydroxytryptamine(5-HT)level were detected via high-performance liquid chromatography with electrochemical detection(HPLC-ECD);the levels of tryptophan(TRP),kynurenine(KYN),and indoleamine 2,3-dioxygenase(IDO)in the hippocampus were detected using enzyme-linked immunosorbent assay(ELISA);the protein expression levels of synaptophysin(SYN)and postsynaptic density material-95(PSD-95)were detected via immunohistochemistry(IHC);and the protein expression levels of N-methyl-D-aspartate receptor(NR)2 A and NR2 B were detected using Western blot.(ii)In vitro experiments:five SPF grade SD pregnant rats(E16–18)were used to obtain primary hippocampal neurons(Ne),six SD new-born rats were used to collected primary astrocytes(As)and microglia(MG),and to establish a Ne-As-MG co-culture system.All co-culture systems were divided into six groups:control(PBS),model[150 mmol/L glucose+200μmol/L corticosterone(G&P)+PBS],blank(G&P+blank serum),positive(G&P+positive drug-containing serum),ZGJTJYF(G&P+ZGJTJYF serum),and 1-methyl-D-tryptophan(1-MT,IDO inhibitor)(G&P+1-MT)groups.After 18 h of intervention by corresponding treatment,immunofluorescence was used to analyze the protein expression levels of SYN,PSD-95,NR2 A,and NR2 B;ELISA was performed to measure the levels of interleukin(IL)-1β,IL-6,tumor necrosis factor(TNF)-α,and TRP/KYN metabolic pathway-related factors[TRP,KYN,kynurenine acid(KYNA),quinolinic acid(QUIN)].Results(i)In vivo experimental results showed that ZGJTJYF-M and ZGJTJYF-L significantly improved the elevated blood glucose state of DD rats(P<0.01 and P<0.05,respectively);ZGJTJYF-H,ZGJTJYF-M,and ZGJTJYF-L increased their autonomous activity,learning,and memory ability(P<0.01,P<0.01,and P<0.05,respectively).Moreover,the levels of 5-HT and TRP were significantly increased(P<0.01),and the levels of KYN and IDO were significantly decreased in the hippocampus(P<0.01)of rats after ZGJTJYF-M treatment.The protein expression levels of SYN and PSD-95 were significantly upregulated in hippocampal neurons(P<0.01),while the abnormal activation of NR2A and NR2B was markedly inhibited in hippocampus(P<0.05)of rats after ZGJTJYF-M treatment.(ii)In vitro experimental results showed that ZGJTJYF-containing serum significantly increased the protein expression levels of SYN and PSD-95 in hippocampal neurons(P<0.01),decreased the levels of IL-1β(P<0.01),IL-6(P<0.05),TNF-α(P<0.01),IDO(P<0.05),KYN(P<0.05),and QUIN(P<0.01),and increased the levels of TRP and KYNA(P<0.01)in the simulated DD state.ZGJTJYF also had an significantly inhibitory effect on the abnormal activation of NR2A and NR2B in neurons(P<0.05)in a stimulated DD state.Conclusion ZGJTJYF can effectively improve 5-HT deficiency in the hippocampus of rats by inhibiting IDO expression and regulating the TRP/KYN metabolic pathway,and it has a favorable protective effect on hippocampal neuron injury caused by DD.Therefore,ZGJTJYF is an effective potential therapeutic drug for the prevention and treatment of DD.

Chemical constituents isolated from the aerial parts of Swertia pseudochinensis and their potential neuroprotective effects

Objective:Swertia pseudochinensis,an annual herb of the genus Swertia in the family Gentianaceae.Some constituents and extracts from the Swertia genus have been recently reported to possess neuroprotective effects,suggesting their potential utility in the prevention and treatment of Parkinson disease(PD).The aim of this work is to identify the chemical constituents and evaluate the potential biological activists of Swertia pseudochinensis.Methods:The phytochemicals from the aerial parts of S.pseudochinensis were isolated and purified by silica gel,Sephadex LH-20 gel,semi-preparative high-performance liquid chromatography,and identified by the spectroscopic methods.All compounds were evaluated for their potential neuroprotective effects against 1-methyl-4-phenylpyridinium-induced apoptosis in the SH-SY5Y human neuroblastoma cell line using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay.Then,we performed an enrichment analysis using the Database for Annotation,Visualization,and Integrated Discovery and investigated the mechanisms by which bellidifolin regulates neurodegenerative disease.Results:Two new anthraquinone,1,5,6-trimethoxy-2-hydroxy-3-methy-anthraquinone(1)and 1,5,6,8-tetramethoxy-2-hydroxy-3-methyanthraquinone(2),together with nine known including 7-O-b-d-glucopyranosyl-1,8-dihydroxy-3-methoxyxanthone(3),gentisin(4),swertianolin(5),bellidifolin(6),gentiacaulein(7),norswertianolin(8),5-O-b-d-glucopyranosyl-1,3,8-trihydroxyapatone(9),1-hydroxy-3,5,8-trimethoxyxanthone(10),and aurantio-obtusin(11),were isolated and compounds 6–8 and 10 exhibited neuroprotective effects at a concentration of 50mmol/L.Among them,bellidifolin showed significant protective activity,and might have potential as a neuroprotective agent for the treatment of PD,possibly by acting on oxidative damage and reactive oxygen species.Conclusions:These findings indicate that further research on the genus Swertia and its bioactive constituents toward neurodegenerative disorders could be extremely rewarding.

Clinical Efficacy and Therapeutic Mechanisms of Traditional Chinese Medicine for Neuroprotection and Neurogenesis in Stroke Treatment

Stroke is the leading cause of human disability with limited effective drugs availability. The disruption of multiple signaling pathways in stroke makes developing new drugs be difficult. Traditional Chinese medicine(TCM) has its unique advantage in targeting multiple signaling pathways with multiple components. Many TCM formulas have the potential for neuroprotection and neurogenesis, but well-designed clinical trials are insufficient and underlying mechanisms unclear. Herein, we introduce the commonly used TCM formulas for stroke treatment and selectively introduce two classic formulas, An Gong Niu Huang(AGNH) pill and Bu Yang Huan Wu Decoction(BYHWD) for neuroprotection and neurogenesis, respectively. Current scientific evidence and clinical trials indicate AGNH pill could be an effective neuroprotective formula as adjunct therapy with relative safety. On the other hand, as a representative TCM formula for post stroke disability, BYHWD could improve the neurological outcome with its neuroprotective and neurogenic effects. The underlying mechanisms could be attributed to the modulation of multiple molecular targets with its multiple components. In conclusion, TCM formulas could be potential adjunct therapies for stroke treatment. The clinical efficacies and molecular mechanisms of promoting neuroprotection and neurogenesis remain to be further studies.

Neuroprotective Effect of Bu-Shen-Huo-Xue Extract against High Glucose-induced Apoptosis in PC12 Cells

Objective： To investigate the neuroprotective effect of Bu-Shen-Huo-Xue （BSHX） extract, a polyherbal formula, against High Glucose （HG）-induced neurotoxicity in PC12 cells. Methods： Cell viability assay, Lactate Dehydrogenase （LDH） assay, Reactive Oxygen Species （ROS） detection, Hoechst 33258, Acridine Orange （AO）/Ethidium Bromide （EB） double stain and Mitochondrial Membrane Potential （MMP） assay were performed. In addition, Bax, Bcl-2, caspase-3, cleaved caspase-3, PARP, cleaved PARP, cytochrome c and Mitogen-Activated Protein Kinases （MAPKs） were detected by western blot. Results： BSHX extract increased cell viability and decreased LDH leakage in a concentration-dependent manner in HG-induced PC12 cells. Moreover, BSHX extract decreased the level of intracellular ROS, increased mitochondrial membrane potential, regulated the expressions of Bax and Bcl-2, and inhibited the release of cytochrome c from mitochondria. Furthermore, BSHX extract attenuated the activation of caspase-3 and PARP, and inhibited the phosphorylations of c-Jun N-terminal kinase （JNK） and p38 MAPKs. Conclusion： BSHX extract exhibited significant neuroprotective effect on HG-induced apoptosis in PC12 cells. This effect may be associated with the suppression of ROS generation as well as mitochondria-mediated caspase and JNK/p38 MAPK signaling pathways.