Inhibition of oxidative phosphorylation in hepatic and cerebral mitochondria of sodium valproate-treated rats

Rats were treated with intraperitoneal injections of sodium valproate (VPA), either acutely, one injection VPA 200 mg/kg, or chronically, VPA 600 mg/kg/day for 5 days, and the oxygen consumption, MO2, of isolated hepatic and cerebral mitochondria measured. For hepatic mitochondria, Stade IV MO2 decreased by more than 20%, and Stage III MO2 by more than 50%, in the presence of succinate or glutamate-malate substrates. A decoupling agent intensified this inhibition. With cerebral mitochondria, the effects were similar but weaker, for pyruvate-malate or glutamate-malate substrates. These findings suggest that VPA, a short-chain fatty acid, may affect the properties of the internal mitochondrial membrane, although an action on substrate carriers, or on indispensable mitochondrial metabolites, is not excluded. Inhibition of oxidative phosphorylation cannot, however, alone account for hepatotoxicities seen in VPA-treated subjects. These are rare, whereas inhibition of mitochondrial respiration by VPA is consistently observed.     

A mathematical analysis of kinetic characteristics of oxidative phosphorylation in the animal brain under hypoxic conditions

The kinetic dependence of the rate of oxidative phosphorylation (ADP/t) on the concentration of exogenous ADP has been mathematically analyzed in the brain mitochondria. This relationship has been approximated by a mathematic model under various vital conditions. We propose an analytical approach to calculating the characteristics of oxidative phosphorylation and predicting the kinetics of oxidative ATP synthesis in brain mitochondria of animals subjected to hypoxia.     

Syringaldehyde exerts neuroprotective effect on cerebral ischemia injury in rats through anti-oxidative and anti-apoptotic properties

There are few studies on the neuroprotective effects of syringaldehyde in a rat model of cerebral ischemia. The study aimed to elucidate the mechanisms underlying the neuroprotective effects of syringaldehyde on ischemic brain cells. Rat models of cerebral ischemia were intraperitoneally administered syringaldehyde. At 6 and 24 hours after syringaldehyde administration, cell damage in the brain of cerebral ischemia rats was obviously reduced, superoxide dismutase activity and nuclear respiratory factor 1 expression in the brain tissue were markedly increased, malondi-adehyde level was obviously decreased, apoptosis-related cysteine peptidase caspase-3 and -9 immunoreactivity was obviously decreased, and neurological function was markedly improved. These ifndings suggest that syringaldehyde exerts neuroprotective effects on cerebral ischemia injury through anti-oxidation and anti-apoptosis.     

Melatonin reduces traumatic brain injur y-induced oxidative stress in the cerebral cortex and blood of rats

Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We investigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vitamin E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain injury-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.     

Control mechanisms in mitochondrial oxidative phosphorylation

Distribution and activity of mitochondria are key factors in neuronal development,synaptic plasticity and axogenesis.The majority of energy sources,necessary for cellular functions,originate from oxidative phosphorylation located in the inner mitochondrial membrane.The adenosine-5’triphosphate production is regulated by many control mechanism-firstly by oxygen,substrate level,adenosine-5’-diphosphate level,mitochondrial membrane potential,and rate of coupling and proton leak.Recently,these mechanisms have been implemented by second control mechanisms, such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes,allosteric inhibition of cytochrome c oxidase,thyroid hormones,effects of fatty acids and uncoupling proteins.Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia.Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5’-triphosphate in response to energy demands.Large amounts of reactive oxygen species are released by defective mitochondria,similarly,decline of antioxidative enzyme activities(e.g.in the elderly) enhances reactive oxygen species production.We reviewed data concerning neuroplasticity,physiology,and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.     

Effects of Jisuikang on hemorheology and inflammatory factors in rats following spinal cord injury*☆

BACKGROUND： Trauma can damage the spinal cord or cauda equina to different degrees. Previous studies have verified that traditional Chinese medicine has effects on spinal cord injury via a variety of pathways. OBJECTIVE： To observe changes in hemorheology and inflammatory factors in spinal cord injury rats following treatment with the Chinese medicine Jisuikang, to verify the dose-dependent effect of Jisuikang, and to compare its effects with the effects of prednisone. DESIGN, TIME AND SETTING： A randomized study was performed at the Research Institute of Orthopedics, and Experimental Center of First Clinical Medical College, Nanjing University of Traditional Chinese Medicine, China from September 2007 to March 2008. MATERIALS： Jisuikang powdered extract, composed of milkvetch root （30 g）, Chinese angelica （12 g）, red peony root （12 g）, earthworm （10 g）, szechwan lovage rhizome （10 g）, peach seed （10 g） and safflower （10 g） was provided by the Experimental Center, First Clinical Medical College, Nanjing University of Traditional Chinese medicine. Each gram of powdered extract was equivalent to 6.47 g crude drug. METHODS： A total of 72 Sprague Dawley rats were randomly assigned into 6 groups （n = 12）. Rat models of spinal cord injury were established using the occlusion method. Rats in the model group were treated with distilled water. Rats in the 25 g/kg, 12.5 g/kg, and 6.25 g/kg Jisuikang groups were given 25 g＆g, 12.5 g/kg, or 6.25 g/kg Jisuikang by gavage, for 14 days. Rats in the prednisone group received 0.06 g/kg prednisone by gavage, for 7 days. Rats in the normal group were given the same volume of distilled water. The volume of administration was 15 mL/kg. MAIN OUTCOME MEASURES： Rat serum interleukin-10, tumor necrosis factor- α （TNF-α ）, nitric oxide, nitric oxide synthase levels, malondialdehyde content, superoxide dismutase activity and whole blood viscosity were measured in each group. Spinal cord around the site of the model was collected. Half the     

Effects of neuroglobin overexpression on mitochondrial function and oxidative stress following hypoxia/reoxygenation in cultured neurons

Neuroglobin (Ngb) is a recently discovered tissue globin with a high affinity for oxygen that is widely and specifically expressed in neurons of vertebrate central and peripheral nervous systems. Our laboratory and others have shown Ngb overexpression can protect neurons against hypoxic/ischemic insults, but the underlying mechanisms remain poorly understood. In this study, we examined the effects of Ngb overexpression on mitochondrial function, oxidative stress, and neurotoxicity in primary cortical neurons following hypoxia/reoxygenation (H/R). Ngb-overexpressing transgenic neurons (Ngb-Tg) were significantly protected against H/R-induced cell death. Rates of decline in ATP levels, MTT reduction, and mitochondrial membrane potential were significantly ameliorated in Ngb-Tg neurons. Furthermore, Ngb overexpression reduced superoxide anion generation after H/R, whereas glutathione levels were significantly improved compared with WT controls. Taken together, these data suggest that Ngb is neuroprotective against hypoxia, in part by improving mitochondria function and decreasing oxidative stress.     

Effects of Jisuikang on hemorheology and inflammatory factors in rats following spinal cord injury

BACKGROUND: Trauma can damage the spinal cord or cauda equina to different degrees. Previous studies have verified that traditional Chinese medicine has effects on spinal cord injury via a variety of pathways. OBJECTIVE: To observe changes in hemorheology and inflammatory factors in spinal cord injury rats following treatment with the Chinese medicine Jisuikang, to verify the dose-dependent effect of Jisuikang, and to compare its effects with the effects of prednisone. DESIGN, TIME AND SETTING: A randomized study was performed at the Research Institute of Orthopedics, and Experimental Center of First Clinical Medical College, Nanjing University of Traditional Chinese Medicine, China from September 2007 to March 2008. MATERIALS: Jisuikang powdered extract, composed of milkvetch root (30 g), Chinese angelica (12 g), red peony root (12 g), earthworm (10 g), szechwan lovage rhizome (10 g), peach seed (10 g) and safflower (10 g), was provided by the Experimental Center, First Clinical Medical College, Nanjing University of Traditional Chinese medicine. Each gram of powdered extract was equivalent to 6.47 g crude drug. METHODS: A total of 72 Sprague Dawley rats were randomly assigned into 6 groups (n = 12). Rat models of spinal cord injury were established using the occlusion method. Rats in the model group were treated with distilled water. Rats in the 25 g/kg, 12.5 g/kg, and 6.25 g/kg Jisuikang groups were given 25 g/kg, 12.5 g/kg, or 6.25 g/kg Jisuikang by gavage, for 14 days. Rats in the prednisone group received 0.06 g/kg prednisone by gavage, for 7 days. Rats in the normal group were given the same volume of distilled water. The volume of administration was 15 mL/kg.MAIN OUTCOME MEASURES: Rat serum interleukin-10, tumor necrosis factor-α (TNF-α), nitric oxide, nitric oxide synthase levels, malondialdehyde content, superoxide dismutase activity and whole blood viscosity were measured in each group. Spinal cord around the site of the model was collected. Half the spinal cord was used for histopathologic examination. The other half was used for measurement of nitric oxide and NOS levels, malondialdehyde contents, and superoxide dismutase activity. RESULTS: Superoxide dismutase activity was higher in the 25 g/kg Jisuikang group than in the model group. Malondialdehyde contents, nitric oxide and NOS levels were lower in the 25 g/kg and 12.5 g/kg Jisuikang groups compared with the model group. Whole blood viscosity was lower in the 25 g/kg and 12.5 g/kg Jisuikang groups compared with the model group (P < 0.05-0.01). Serum TNF-α content was lower in each Jisuikang group compared with the model group (P < 0.05-0.01). Serum interleukin-10 levels were greater in the prednisone group and each Jisuikang group compared with the model group (P < 0.01). Mild hemorrhage and necrosis in the rat spinal cord, and unclear neural cell swelling were seen in the 25 g/kg Jisuikang group. Severe hemorrhage and necrosis in the rat spinal cord, and distinct neural cell swelling were seen in the 12.5 g/kg Jisuikang group. Edema in the white matter was found in the 6.25 g/kg Jisuikang group. Pathological changes in the prednisone group were identical to the 25 g/kg and 12.5 g/kg Jisuikang groups. CONCLUSION: Jisuikang inhibits nitric oxide synthase expression, reduces nitric oxide and TNF-α levels, decreases malondialdehyde content, increases interleukin-10 levels and superoxide dismutase activity, improves indices of hemorheology, and prevents secondary changes in spinal cord injury, resulting in relieving pathological changes in spinal cord tissue. The outcome was significant in the 25 g/kg Jisuikang group compared with the 12.5 g/kg Jisuikang group.     

Influence of thyroid hormone treatment on the respiratory activity of cerebral mitochondria from hypothyroid rats. A critical re-assessment

Effects of treatment with thyroid hormones L-3,5,3'-tri-iodothyronine (T3) and L-thyroxine (T4) on oxidative energy metabolism in cerebral mitochondria from hypothyroid adult rats were examined. It was observed that T3 and T4 stimulated respiratory activity in a substrate-specific and dose-dependent manner. The results also suggest that the synthesis of cytochrome aa3 and of cytochrome c may be dependent on both T3 as well as T4 whereas higher concentrations than normal of T3 and T4 may have a catabolic influence on cytochrome b content.     

Fetal bovine serum versus Chinese herbal formula Naoluoxintong serum supplementation for proliferation and differentiation of rat embryonic neural stem cells

BACKGROUND: How to induce endogenous neural stem cells (NSCs) to differentiate into needed neural cell types is a hot spot of current researches.OBJECTIVE: To compare differences between fetal bovine serum and Chinese herbal formula Naoluoxintong serum supplementation for inducing proliferation and differentiation in rat embryonic NSCs.DESIGN, TIME AND SETTING: An in vitro, serum pharmacology, comparative, observation study was performed from March to September in 2008 at the Laboratory of Neurodegenerative Diseases,College of Life Science in University of Science and Technology of China, the Key Laboratory Breeding Base of Acupuncture Foundation and Technology in Anhui University of Traditional Chinese Medicine, the Anhui Province Key Laboratory of R & D of Chinese Medicine, and at the Level 3 Laboratory of Molecular Biology of the State Administration of Traditional Chinese Medicine.MATERIALS: The Chinese herbal formula Naoluoxintong was produced by Radix Astragali, Radix Notoginseng, Rhizoma Chuanxiong, Scolopendra at Anhui University of Traditional Chinese Medicine. Mouse anti-rat nestin, glial fibrillary acidic protein, and galactocerebroside monoclonal antibodies, as well as rabbit anti-neuron-specific enolase polyclonal antibody were produced by Chemicon, Billerica, MA, USA. METHODS: Wistar rats aged 3 months were intragastrically infused with Naoluoxintong. Wistar rat embryonic NSCs (passage 8) were induced to proliferate and differentiate using 10% fetal bovine serum, 10% Naoluoxintong serum, and 10% rat serum.MAIN OUTCOME MEASURES: Phenotypic changes in cultured cells were detected using phase contrast microscopy, and cell proliferation and differentiation were observed using immunofluorescence staining.RESULTS: Proliferation and differentiation of embryonic NSCs was induced by three different types of blood serum. Although the differentiation time course with Naoluoxintong serum was later than with the other two methods, the differentiated cells were morphologically similar to mature neurons to a greater extent.CONCLUSION: Naoluoxintong serum supplementation induced differentiation of NSCs into neuronal-like cells and stimulated neuronal maturation.     

Protective effect of oxysophoridine on cerebral ischemia/reperfusion injury in mice

Oxysophoridine, a new alkaloid extracted from Sophora alopecuroides L., has been shown to have a protective effect against ischemic brain damage. In this study, a focal cerebral ischemia/reperfusion injury model was established using middle cerebral artery occlusion in mice. Both 62.5, 125, and 250 mg/kg oxysophoridine, via intraperitoneal injection, and 6 mg/kg nimodipine, via intragastric administration, were administered daily for 7 days before modeling. After 24 hours of reperfusion, mice were tested for neurological deficit, cerebral infarct size was assessed and brain tissue was collected. Results showed that oxysophoridine at 125, 250 mg/kg and 6 mg/kg nimodipine could reduce neurological deficit scores, cerebral infarct size and brain water content in mice. These results provided evidence that oxysophoridine plays a protective role in cerebral ischemia/reperfusion injury. In addition, oxysophoridine at 62.5, 125, and 250 mg/kg and 6 mg/kg nimodipine increased adenosine-triphosphate content, and decreased malondialdehyde and nitric oxide content. These compounds enhanced the activities of glutathione-peroxidase, superoxide dismutase, catalase, and lactate dehydrogenase, and decreased the activity of nitric oxide synthase. Protein and mRNA expression levels of N-methyl-D-aspartate receptor subunit NR1 were markedly inhibited in the presence of 250 mg/kg oxysophoridine and 6 mg/kg nimodipine. Our experimental findings indicated that oxysophoridine has a neuroprotective effect against cerebral ischemia/reperfusion injury in mice, and that the effect may be due to its ability to inhibit oxidative stress and expression of the N-methyl-D-aspartate receptor subunit NR1.     

A meta-analysis of Chinese herbal medicines for vascular dementia

OBJECTIVE: To investigate the efficacy and safety of Chinese herbal medicines in the treatment of patients with vascular dementia. DATA RETRIEVAL: We retrieved publications from Cochrane Library (2004 to July 2011), PubMed (1966 to July 2011), the Chinese Science and Technique Journals Database (1977 to July 2011), the China National Knowledge Infrastructure (1979 to July 2011), Google Scholar (July 2011), and the Chinese Biomedical Database (1977 to July 2011) using the"Chinese medicine OR Chinese herbal medicine" and "vascular dementia OR mild cognition impair OR multi-infarct dementia OR small-vessel dementia OR strategic infarct dementia OR hypoperfusion dementia OR hemorrhagic dementia OR hereditary vascular dementia". SELECTION CRITERIA: Randomized controlled trials comparing Chinese herbal medicines with placebo/western medicine in the treatment of patients with vascular dementia were included. Diagnostic standards included Diagnostic and Statistical Manual of Mental Disorders-IV, and National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l’Enseignement en Neurosciences. Two participants independently conducted literature screening, quality evaluation and data extraction. The quality of each trial was assessed according to the Cochrane Reviewers’ Handbook 5.0. MAIN OUTCOME MEASURES: Effective rate, Mini-Mental State Examination scores, Hasegawa Dementia Scale scores, and incidence of adverse reactions. RESULTS: We identified 1 143 articles discussing the effects of Chinese medicine on vascular dementia. Thirty-one of these were included in the analysis. These studies involved a total of 2 868 participants (1 605 patients took Chinese medicine decoctions (treatment group); 1 263 patients took western medicine or placebo). The results of our meta-analysis revealed that Chinese herbal remedies in the treatment group were more efficacious than the control intervention (relative risk (RR)=1.27; 95% confidence interval (CI): 1.18-1.38, P<0.01). Mini-Mental State Examination scores were higher in patients taking Chinese herbal medicines than in those in the control group (weighted mean difference (WMD)=2.83; 95%CI: 2.55-3.12, P<0.01). Patients in the treatment group showed better disease amelioration than those in the control group (Hasegawa Dementia Scale scores; WMD=2.41, 95%CI: 1.48-3.34, P<0.01). There were also considerably fewer adverse reactions among those in the treatment group compared with those in the control group (RR=0.20, 95%CI: 0.08-0.47, P<0.01). CONCLUSION: Chinese herbal medicine appears to be safer and more effective than control measures in the treatment of vascular dementia. However, the included trials were generally low in quality. More well-designed, high-quality trials are needed to provide better evidence for the assessment of the efficacy and safety of Chinese medicines for vascular dementia.     

Mailuoning suppresses H2O2-induced cortical neuronal injury and correlates with increased catalase activity and inhibited oxidative stress function

BACKGROUND:Mailuoning, a Chinese herb, has been widely used in China to treat acute ischemic stroke, and the major component exhibits anti-oxidative effects. However, the precise anti-oxidation pathway remains uncertain.OBJECTIVE:To validate the protective effects of Mailuoning on H202-induced primary cortical neuron injury in embryonic mice.DESIGN, TIME AND SETTING:Comparative observation and in v#ro experiments were performed at the Jiangsu Key Laboratory for Molecular Medicine from January 2008 to September 2009.MATERIALS:Mailuoning (Nanjing Jinling Medical Company, China), reactive oxygen species (ROS) kit (Beyotime Biotechnology, China), superoxide dismutase (SOD), Cu/Zn SOD kit, malondialdehyde (MDA) kits (Nanjing Jiancheng, China), mitochondrial membrane potential (GMS10013.1, GENMED, USA) and catalase activity assay kit (Beyotime Biotechnology, China) were utilized for the present study.METHODS:Mouse embryonic cortical neurons were isolated and cultured with culture medium containing H2O2 (80 μmol/L) and/or Mailuoning (1.25 μg/mL) for 24 hours.MAIN OUTCOME MEASURES:Neuronal viability and death were detected by methyl thiazolyl tetrazdium and flow cytometry; ROS production was determined by flow cytometry; mitochondriai membrane potential was detected using fluorescent staining; SOD activity was detected using a modified nitroblue tetrazolium method; Cu/Zn SOD and catalase activity was detected by spectrophotometry; and MDA was determined using the lipid peroxidation method.RESULTS:H2O2 increased ROS production and MDA concentration (P < 0.05), and decreased mitochondrial membrane potential, SOD, Cu/Zn SOD and catalase activity (P < 0.05); the number of surviving neurons (P < 0.05) was also reduced. Mai/uoning reversed these changes.CONCLUSION:Mailuoning protects H2O2-induced injury in cortical cells by inhibiting ROS and MDA, increasing depolarization of mitochondrial membrane, and enhancing SOD and catalase activity.     

Effects of Fujian tablet on Nogo-A mRNA expression and plasticity of the corticospinal tract in a rat model of focal cerebral ischemia

The present study investigated the effects of Fujian tablet, a Chinese medicine compound that can nourish liver and kidney, on corticospinal tract plasticity and cervical cord microenvironment in rats with focal cerebral ischemia. Results showed that motor function of rats with right proximal middle cerebral artery occlusion was significantly improved following treatment with Fujian tablet, 9 g crude drug/kg. Anterograde tracing revealed significantly increased biotinylated dextran amine expression in the denervated (left) side of the cervical cord (C4-6) following Fujian tablet treatment, and significantly decreased Nogo-A mRNA expression was detected in the denervated side of the cervical cord (C4-6) using in situ hybridization. Pearson’s correlation analysis showed a negative correlation between biotinylated dextran amine and Nogo-A mRNA expression (r = -0.943, P < 0.01). Results demonstrated that Fujian tablet can promote corticospinal tract plasticity possibly through the inhibitory effect on Nogo-A mRNA expression in the cervical spinal cord, thereby improving motor dysfunction.     

Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia

Resveratrol possesses beneficial biological effects,which include anti-oxidant,anti-inflammatory and anti-carcinogenic properties.Recently,resveratrol has been shown to exhibit neuroprotective effects in models of Parkinson’s disease,cerebral ischemia and Alzheimer’s disease.However,its effects on vascular dementia remain unclear.The present study established a rat model of vascular dementia using permanent bilateral common carotid artery occlusion.At 8-12 weeks after model induction,rats were intragastrically administered 25 mg/kg resveratrol daily.Our results found that resveratrol shortened the escape latency and escape distances in the Morris water maze,and prolonged the time spent percentage and swimming distance percentage in the target quadrant during the probe test,indicating that resveratrol improved learning and memory ability in vascular dementia rats.Further experiments found that resveratrol decreased malonyldialdehyde levels,and increased superoxide dismutase activity and glutathione levels in the hippocampus and cerebral cortex of vascular dementia rats.These results confirmed that the neuroprotective effects of resveratrol on vascular dementia were associated with its anti-oxidant properties.     

肢体缺血后处理对糖尿病大鼠脑缺血再灌注损伤线粒体结构和功能的影响

目的探讨肢体缺血后处理(I-PostC)诱导的远隔器官I-PostC(RPostC)对糖尿病大鼠局灶性脑缺血再灌注(I/R)损伤线粒体结构和功能的影响。方法链脲佐菌素空腹腹腔注射制作糖尿病大鼠模型,线栓法闭塞大脑中动脉(MCAO)制作局灶性I/R大鼠模型。造模成功的40只雄性SD大鼠分为4组:空白对照组、假手术组、I/R组,RPostC组,每组10只。I/R6h后取脑组织行HE染色观察,测定线粒体丙二醛(MDA)含量、超氧化物歧化酶(SOD)、Na+/K+-ATP酶、Ca2+-ATP酶和谷胱甘肽过氧化物酶(GSH-Px)活性,观察线粒体超微结构的改变。结果I/R组线粒体MDA含量[(4.99±1.25)nmol/mgprot]较空白对照组和假手术组明显升高(均P<0.01),SOD[(72.52±13.07)U/mg]、Na+/K+-ATP酶[(3.17±0.34)μmolPi/(mg.h)]、Ca2+-ATP酶[(1.56±0.23)μmolPi/(mg.h)]和GSH-Px活性[(22.66±5.29)U/mg)]明显降低(均P<0.01);与I/R组比较,RPostC组MDA含量[(3.58±0.91)...     

Protective effects of kidney-tonifying Chinese herbal preparation on substantia nigra neurons in a mouse model of Parkinson’s disease

The Chinese herbs Herba Epimedii, Fructus Ligustri Lucidi and Rhizoma Polygonati were injected into Parkinson’s disease mice established via intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride. The selective monoamine oxidase B inhibitor selegiline was used as a positive control drug. After successive administration for 4 weeks, Herba Epimedii could downregulate the expression of caspase-3 and increase the brain-derived neurotrophic factor level, as well as increase tyrosine hydroxylase activity in the substantia nigra of Parkinson’s disease mouse models. Rhizoma Polygonati could downregulate the expression of caspase-3 and FasL, and increase neural growth factor and brain-derived neurotrophic factor levels. Fructus Ligustri Lucidi could downregulate caspase-3 expression. Rhizoma Polygonati and Fructus Ligustri Lucidi did not produce obvious effects on tyrosine hydroxylase activity. Herba Epimedii and Fructus Ligustri Lucidi yielded similar effects on apoptosis-promoting factors to those elicited by selegiline. Herba Epimedii and Rhizoma Polygonati significantly increased the levels of neurotrophic factors compared with selegiline. Herba Epimedii significantly increased tyrosine hydroxylase activity compared with selegiline. It is indicated that the kidney-tonifying Chinese herbal preparation can downregulate the expression of apoptosis-promoting factors, increase neurotrophic factors levels in the substantia nigra and striatum, as well as increase tyrosine hydroxylase activity in the substantia nigra of Parkinson’s disease mouse models, thereby exerting a stronger or similar neuroprotective effects compared with selegiline.     

An optimal dose of tea polyphenols protects against global cerebral ischemia/reperfusion injury

Previous studies addressing the protection of tea polyphenols against cerebral ischemia/ reperfusion injury often use focal cerebral ischemia models, and the optimal dose is not unified. In this experiment, a cerebral ischemia/reperfusion injury rat model was established using a modified four-vessel occlusion method. Rats were treated with different doses of tea polyphenols (25, 50, 100, 150, 200 mg/kg) via intraperitoneal injection. Results showed that after 2, 6, 12, 24, 48 and 72 hours of reperfusion, peroxide dismutase activity and total antioxidant capacity in brain tissue gradually increased, while malondialdehyde content gradually decreased after tea polyphenol intervention. Tea polyphenols at 200 mg/kg resulted in the most apparent changes. Terminal deoxynucleotidyl transferase-mediated nick end labeling and flow cytometry showed that 200 mg/kg tea polyphenols significantly reduced the number and percentage of apoptotic cells in the hippocampal CA1 region of rats after cerebral ischemia/reperfusion injury. The open field test and elevated plus maze experiments showed that tea polyphenols at 200 mg/kg strengthened exploratory behavior and reduced anxiety of cerebral ischemia/reperfusion injured rats. Experimental findings indicate that tea polyphenols protected rats against cerebral ischemia/ reperfusion injury and 200 mg/kg is regarded as the optimal dose.