• Journal of Ginseng Research
• /
• v.46 no.4
• /
• pp.515-525
• /
• 2022

Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca²⁺]_i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca²⁺]_i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

• The Korea Journal of Herbology
• /
• v.32 no.1
• /
• pp.25-31
• /
• 2017

Objectives : Mori Radicis Cortex (MRC), the root epidermis of Morus alba L., has been traditionally used to treat lung-related diseases in Korean Medicine. The common of MRC is Mulberry bark Morus bark, and it's pharmaceutical properties and taste are known as sweet and cold, and it promotes urination and reduce edema by reducing heat from the lungs and soothe asthma. In the present study, anti-apoptotic mechanism of MRC in middle cerebral artery occlusion (MCAO) model in mice. Methods : Two-hundred grams of MRC was extracted with methanol at room temperature for 5 days, and this was repeated one time. After filtration, the methanol was removed using vacuum evaporator, then stored at $-20^{\circ}C$ until use. C57BL/6 male mice were housed in an environment with controlled humidity, temperature, and light cycle. In order to determine beneficial effects of MRC on ischemia induced brain damage, infarct volume, neurological deficit scores, activities of several apoptosis-related proteins such as caspase-8, -9, Bcl-xL in MCAO-induced brains of mice were analyzed. Mice in MRC-treated groups were orally administered 30, 100, or 300 mg/kg of body weight for three consecutive days before commencing the MCAO procedure. Results : Pre-treatment of MRC significantly reduced infarct volume in MCAO subjected mice applied with 300 mg/kg of MRC methanol extract, and MRC effectively inhibited Bcl-xL reduction and caspase-9 activation caused by MCAO-induced brain damage. Conclusions : MRC showed neuro-protective effects by regulating apoptosis-related protein signals, and it can be a potential candidate for the therapy of ischemia-induced brain damage.

• Journal of agriculture & life science
• /
• v.46 no.6
• /
• pp.137-146
• /
• 2012

This study investigated whether ferulic acid modulates the heme oxygenase (HO)-1 and HO-2 expression in middle cerebral artery occlusion (MCAO)-induced brain injury. Rats (Sprague-Dawley, male) were treated with vehicle or ferulic acid (100 mg/kg, i.v.) before MCAO, and cerebral cortex tissues were collected 24 h after MCAO. This study clearly confirmed the protective effects of ferulic acid during MCAO-induced damage using hematoxylin and eosin staining. MCAO induces nuclear chromatin condensations and necrotic changes with scalloped shrunken form. However, ferulic acid prevented MCAO-induced histopathological changes. HO-1 and HO-2 expression levels were measured using reverse-transcription PCR and Western blot analyses. HO-1 levels were decreased in vehicle-treated animals after MCAO, whereas this decrease in HO-1 levels was attenuated by ferulic acid treatment. However, the level of HO-2 was consistently maintained in the cerebral cortex of vehicle- and ferulic acid-treated animals after MCAO. These results demonstrated that ferulic acid regulates HO-1 expression in ischemic brain injury, while ferulic acid do not modulate HO-2 expression in MACO. In conclusion, these findings suggest that ferulic acid exerts a neuroprotective effect by preventing the MCAO-induced decrease of HO-1 expression.

• Journal of Chest Surgery
• /
• v.30 no.8
• /
• pp.752-759
• /
• 1997

Profound hypothermia protects . cerebral function during total circulatory arrest(TCA) in the surgical treatment of a variety of cardiac and aortic diseases. Despite its importance, there is no ideal technique to monitor the brain injury from ischemia. Since 1994, we have developed compressed spectral array(CSA) of electroencephalography(EEG) and monitored cerebral activity to reduce ischemic injury. The purposes of this study are to analyse the efficacy of CSA and to establish objective criteria to consistently identify the safe level of temperature and arrest time. We studied 6 patients with aortic dissection(AD, n=3) or aortic arch aneurysm(n=3, ruptured in 2). Body temperatures from rectum and esophagus and the EEG were monitored continuously during cooling and rewarming period. TCA with cerebral ischemia was performed in 3 patients and TCA with selective cerebral perfusion was performed in 3 patients. Total ischemic time was 30, 36 and 56 minutes respectively for TCA group and selective perfusion time was 41, 56 and 92 minutes respectively for selective perfusion group. The rectal temperatures for flat EEG were between 16.1 and 22. $1^{\circ}C$ (mean: 18.4 $\pm$ 2.0): the esophageal temperatures between 12.7 and $16.4^{\circ}C$ (mean $14.7\pm1.6).$ The temperatures at which EEG reappeared $5~15.4^{\circ}C$ for esophagus. There was no neurological defic t and no surgical mortality in this series. In summary, the electrical cerebral activity Teappeared within 23 minutes at the temperature less than $16^{\circ}C$ for rectum. It seemed that $15^{\circ}C$ of esophageal temperature was not safe for 20 minutes of TCA and continuous monitoring the EEG with CSA to identify the electrocerebral silence was useful.

• Herbal Formula Science
• /
• v.22 no.1
• /
• pp.13-32
• /
• 2014

Objectives : Until now the study of Cnidii Rhizoma, hemorrhage, brain waves, such as ischemic brain injury, analgesic, effect overcome of the stress from pregnancy melanin formation and inhibiting effects skin whitening have been published regarding this article. Cnidii Rhizoma demonstrates its different abilities depending on the characteristics. This paper reported that effect of Cnidii Rhizoma in Dongeuibogam blended prescriptions as main medicine. In addition, by analyzing data, we studied about utilizing of Cnidii Rhizoma. Methods : Cnidii Rhizoma in Dongeuibogam Prescriptions as the main ingredient was built with database of 202 prescriptions. Thus analyzed data was summarized in detail.(Table-1) If there is no difference in the title of the prescription but in other case the configuration information is different, formulations 1 and 2 were divided by the table. Results : The following results were reached through investigations on the prescriptions usikng Cnidii Rhizoma as a key component. 1. Prescriptions taking Cnidii Rhizoma as a monarch drug are utilized for 40 therapeutic purposes. In particular, 12.3% of prescriptions appear in the chapter of head, and 10.8% of those appear in the chapter of women, and 9.4% of eye, 8.9% of child, 6.4% of wind disease respectively. 2. Prescriptions utilizing Cnidii Rhizoma as the main ingredient are used in the treatment of headache, dizziness and pregnancy hemorrhage fetal movement, premature birth and they are also used for treating 131 different types of disease. 3. The dosage of Cnidii Rhizoma in formulas is from 2pun(about 0.75g) to 5don(nearly 18.75g), however 1don(nearly 3.75g) has been taken the most for clinical application. 4. We find out that according to herbs or prescriptions, Cnidii Rhizoma has a variety of functions such as ascending & descending of energy. Samultang is the most useful base prescription which used the Cnidii Rhizoma as the main component. Conclusion : These results suggest that, Cnidii Rhizoma once-amount use (don nearly 3.75g) 4g in head, gynecology, ophthalmology, pediatrics and paralysis disease associated with oriental medicine resource development can be considered to be widely used These results suggest that Cnidii Rhizoma was used most with 1 don(4g) and can be widely used for the resource development to the disease such as brain, gynecology, ophthalmologhy, pediatrics and wind-associated symptoms.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.22 no.4
• /
• pp.993-999
• /
• 2008

Ischemic brain injury such as cerebral infarction is characterized by acute local inflammatory response mediated by cytokines. The mechanism of cytokines involved in cerebral infarction progression are uncompletely revealed yet. We investigated to find out the relationship between single nucleotide polymorphism (SNP) of interleukin 4 receptor(IL4R) and Oriental Medicine therapy efficacy in patients with cerebral infarction for 2 weeks. Oriental Korean Medicine therapies (herbal medicine and acupuncture) were applied daily and motor functions of patients were assessed using the modified cerebral vascular accident (MCVA) scores. Genotyping for IL4R polymorphism was done by pyrosequencing analysis. In IL4R genotypes and the frequency of alleles, there was no significant difference between cerebral infarction patients (n=124) and controls group (n=175). And there was also no significant difference among good and bad responders in cerebral infarction patients. In this study the IL4R genotype might not be the risk factor or a good predictive genetic marker for good and bad responders in cerebral infarction patients in Korean. Further studies including different cytokine genes will be necessary for the exact genetic markers.

• Journal of International Academy of Physical Therapy Research
• /
• v.2 no.1
• /
• pp.193-200
• /
• 2011

This study is intended to examine the tDCS and Montoya stair task(MST) on sensorimotor recovery and glial scar expression in MCAo induced stroke model of rat. To achieve this goal, this study selected 80 SD rats of 8 weeks. The experiment groups were divided them into four groups, and assigned 20 rats to each group. Group I was a experimental control group; GroupII was a tDCS application group after MCAo; Group III was a MST application group after MCAo; Group IV was a tDCS and MST application group after MCAo. In each group, neurological function test measurement, motor behavior test, montoya stair task test, immunohistochemistric finding of GFAP expression finding were analyzed. In motor behavior test, the outcome of group I was significantly difference than the other group, especially from 14days. In montoya stair task test, the outcome of group I was significantly lower than the other group especially, group II were significantly different on 14days and group IV was most significantly difference than the other group. In immunohistochemistric finding, group II, III, IV were decrease GFAP expression on depend on time stream. These results throughout the MCAo due to focal ischemic brain injury rat model four weeks tDCS and MST was applied, when the neurobehavioural, upper extremity function and ability, histopathologic data suggest that sensorimotor function recovery and a positive influence on glial scar decrease and confirmed that.

• Clinical and Experimental Pediatrics
• /
• v.55 no.7
• /
• pp.238-248
• /
• 2012

Purpose: Hypoxic-ischemic encephalopathy is an important cause of neonatal mortality, as this brain injury disrupts normal mitochondrial respiratory activity. Carnitine plays an essential role in mitochondrial fatty acid transport and modulates excess acyl coenzyme A levels. In this study, we investigated whether treatment of primary cultures of rat cortical neurons with L-carnitine was able to prevent neurotoxicity resulting from oxygen-glucose deprivation (OGD). Methods: Cortical neurons were prepared from Sprague-Dawley rat embryos. L-Carnitine was applied to cultures just prior to OGD and subsequent reoxygenation. The numbers of cells that stained with acridine orange (AO) and propidium iodide (PI) were counted, and lactate dehydrogenase (LDH) activity and reactive oxygen species (ROS) levels were measured. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the terminal uridine deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were performed to evaluate the effect of L-carnitine (1 ${\mu}M$, 10 ${\mu}M$, and 100 ${\mu}M$) on OGD-induced neurotoxicity. Results: Treatment of primary cultures of rat cortical neurons with L-carnitine significantly reduced cell necrosis and prevented apoptosis after OGD. L-Carnitine application significantly reduced the number of cells that died, as assessed by the PI/AO ratio, and also reduced ROS release in the OGD groups treated with 10 ${\mu}M$ and 100 ${\mu}M$ of L-carnitine compared with the untreated OGD group (P<0.05). The application of L-carnitine at 100 ${\mu}M$ significantly decreased cytotoxicity, LDH release, and inhibited apoptosis compared to the untreated OGD group (P<0.05). Conclusion: L-Carnitine has neuroprotective benefits against OGD in rat primary cortical neurons in vitro.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.19 no.6
• /
• pp.1666-1672
• /
• 2005

Oriental medicinal drugs have a broad spectrum of clinical use for the cure of nervous system diseases including brain ischemic damages or neuropathies. Yet, specific drugs or drug components used in the oriental medicine in relation to none fiber regeneration are not known. In the present study, possible growth promoting effects of oriental medicinal drugs were investigated in the injured sciatic nerve system in the rat. By immunofluorescence staining, we found that Jahageo (JHG, Hominis placenta) increased Induction levels of axonal growth associated protein GAP-43 in the rat sciatic none. Small growth promoting activity was found in Golsebo (GSB, Drynariae rhizoma) and Baikhasuo (BHSO, Polygoni multiflori radix) drugs. JHG also increased cell cycle protein Cdc2 levels in the injured area of the sciatic nerves. Immunofluorescence staining indicated that induced Cdc2 protein was mostly localized in the Schwann cells in the injury area, implying that JHG activity might be related to increased Schwann cell proliferation during axonal regeneration. Moreover, levels of phospho-extracellular signal-regulated (ERK) pathway in the injured neNes were elevated by JHG treatment while levels of total ERK were unaltered. In vivo measurement of axonal regeneration using retrograde tracer showed that JHG, GSB and BHSO significantly enhanced Dil-labeled regenerating motor neurons compared with saline control. The present data suggest that oriental medicinal drugs such as JHG, GSB, and BHSO may be a useful target for developing specific drugs of axonal regeneration.

• Journal of Ginseng Research
• /
• v.43 no.2
• /
• pp.326-334
• /
• 2019

Background: The objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells. Methods: The neuroprotective effect of ginsenosides were evaluated by measuring cell viability. Protein expressions of mitogen-activated protein kinase (MAPK), Bcl2, Bax, and apoptosis-inducing factor (AIF) were determined by Western blot analysis. The occurrence of apoptotic and death cells was determined by flow cytometry. Cellular level of $Ca^{2+}$ and reactive oxygen species (ROS) levels were evaluated by image analysis using the fluorescent probes Fluor-3 and 2',7'-dichlorodihydrofluorescein diacetate, respectively. In vivo efficacy of neuroprotection was evaluated using the Mongolian gerbil of ischemic brain injury model. Result: Reduction of cell viability by glutamate (5 mM) was significantly suppressed by treatment with ginsenoside Rb2. Phosphorylation of MAPKs, Bax, and nuclear AIF was gradually increased by treatment with 5 mM of glutamate and decreased by co-treatment with Rb2. The occurrence of apoptotic cells was decreased by treatment with Rb2 ($25.7{\mu}M$). Cellular $Ca^{2+}$ and ROS levels were decreased in the presence of Rb2, and in vivo data indicated that Rb2 treatment (10 mg/kg) significantly diminished the number of degenerated neurons. Conclusion: Our results suggest that Rb2 possesses neuroprotective properties that suppress glutamate-induced neurotoxicity. The molecular mechanism of Rb2 is by suppressing the MAPKs activity and AIF translocation.