• 생약학회지
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• 제48권4호
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• pp.304-313
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• 2017

These days, as the average span of population's life increases, the number patients of dementia also increases. But Research on Korean medicine is stilled limited. The research evaluates the effect of the extract from Cornus officinalis S.et Z on cognitive impairment induced by scopolamine in mice. The mice were randomly divided into five groups of ten mice. The normal group was treated with only 0.9% saline. The control group was treated with scopolamine (5 mg/kg, i.p.). The positive control group was treated with tacrin. The C100, 200 group was treated with C. officinalis extracts 100, 200 mg/kg. Memory-related behaviors were evaluated using a morris water maze and a passive avoidance test. Protein levels of BDNF, p-CREB (ser133), immunohistochemistry staining, and cholinergic activities were measured in brain tissue. The effects of C. officinalis extract significantly increased acetylcholine concentration and decreased acetylcholinesterase activity. The C. officinalis extract affected memory formation. Also, to confirm expression of protein BDNF, p-CREB (ser133) in the hippocampus, the researchers observed that immunohistochemistry and western blot increased in C. officinalis extract. These results suggest that C. officinalis provides a significant neuroprotective effect against scopolamine-induced cholinergic system and cognitive impairment.

• Animal cells and systems
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• 제13권4호
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• pp.357-362
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• 2009

Hesperidin, the most abundant polyphenolic compound found in citrus fruits, has been known to possess neuroprotective, sedative, and anticonvulsive effects on the nervous system. In a recent electrophysiological study, it was reported that hesperidin induced biphasic change in population spike amplitude in hippocampal CA1 neurons in response to both single spike stimuli and theta-burst stimulation depending on its concentration. However, the precise mechanism by which hesperidin acts on neuronal functions has not been fully elucidated. Here, using whole-cell patch-clamp recording, we revealed that hesperidin did not affect excitatory synaptic activities such as basal synaptic transmission and theta-burst LTP. Moreover, in a current injection experiment, spike number, resting membrane potential and action potential threshold also remained unchanged. Taken together, these results indicate that the effects of hesperidin on the neuronal functions such as spiking activity might not be attributable to either modification of excitatory synaptic transmissions or changes in membrane excitability in hippocampal CA1 neuron.

• 약학회지
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• 제46권3호
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• pp.185-191
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• 2002

Alzheimer's disease (AD) involves neuronal degeneration with impaired cholinergic transmission, particularly in areas of the brain associated with learning and memory. Several cholinesterase inhibitors are widely prescribed to ameliorate the cognitive deficits in AD patients. In an attempt to examine if tacrine and donepezil, two well-known cholinesterase inhibitors, exhibit additional pharmacological actions in primary cultured rat cortical cells, we investigated the effects on neuronal injuries induced by glutamate or N-methyl-D-aspartate (NMDA), $\beta$-amyloid fragment ( $A_{{beta}25-35)}$), and various oxidative insults. Both tacrine and donepezil did not significantly inhibit the excitotoxic neuronal damage induced by glutamate. However, tacrine inhibited the toxicity induced by NMDA in a concentration-dependent fashion. In addition, tacrine significantly inhibited the $A_{{beta}25-35)}$-induced neuronal injury at the concentration of 50 $\mu$M. In contrast, donepezil did not reduce the NMDA- nor $A_{{beta}25-35)}$-induced neuronal injury. Tacrine and donepezil had no effects on oxidative neuronal injuries in cultures nor on lipid peroxidation in vitro. These results suggest that, in addition to its anticholinesterase activity, the neuroprotective effects by tacrine against the NMDA- and $A_{{beta}25-35)$-induced toxicity may be beneficial for the treatment of AD. In contrast, the potent and selective inhibition of central acetylcholinesterase appears to be the major action mechanism of donepezil.

• 약학회지
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• 제47권6호
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• pp.369-375
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• 2003

Xiaoshuan Zaizao Wan (XZW) has been used in China to improve hemiplegia, deviation of eye and mouth, and dysphasia due to cerebral thrombosis. To characterize pharmacological actions of XZW, we evaluated its effects on neuronal cell damage induced in primary cultured rat cortical cells by various oxidative insults, glutamate or N-methyl-D-aspartate (NMDA), and $\beta$-amyloid fragment ($A_{\beta(25-35)}$). XZW was found to inhibit the oxidative neuronal damage induced by $H_2O_2$, xanthine/xanthine oxidase, or $Fe^{2+}$/ascorbic acid. It also attenuated the excitotoxic damage induced by glutamate or NMDA. The NMDA-induced neurotoxicity was more effectively inhibited than the glutamate-induced toxicity. In addition, we found that XZW protected neurons against the $A_{\beta(25-35)}$-induced toxicity. Moreover; XZW exhibited dramatic inhibition of lipid peroxidation in rat brain homogenates and mild 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. Taken together; these results demonstrate that XZW exerts neuroprotective effects against oxidative, excitotoxic, or $A_{\beta(25-35)}$-induced neuronal damage. These findings may provide pharmacological basis for its clinical usage treating the sequelae caused by cerebral thrombosis. Furthermore, XZW may exert beneficial effects on Alzheimer's disease and other oxidative stress-related neurodegenerative disorders.

• 대한약침학회지
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• 제23권2호
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• pp.79-87
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• 2020

Objectives: Ginsenosides found in ginseng, and the hydrolysates derived from their conversion, exhibit diverse pharmacological characteristics [1]. These have been shown to include anti-cancer, anti-angiogenic, and anti-metastatic effects, as well as being able to provide hepatic and neuroprotective effects, immunomodulation, vasodilation, promotion of insulin secretion, and antioxidant activity. Therefore, the purpose of this study was to examine how quickly the ginsenosides decompose and what kinds of degradation products are created under physicochemical processing conditions that don't involve toxic chemicals or other treatments that may be harmful. Methods: The formation of ginsenoside-Rg2 and ginsenoside-Rg3 was examined. These demonstrated diverse pharmacological effects. Results: We also investigated physicochemical factors affecting their conversion. The heating temperatures and times yielding the highest concentration of ginsenosides (-Rb1, -Rb2, -Rc, -Rd, -Rf, -Rg1, and -Re) were examined. Additionally, the heating temperatures and rates of conversion of these ginsenosides into new 'ginseng saponins', were examined. Conclusion: In conclusion, obtained provide us with effective technology to control the concentration of both ginsenosides and the downstream converted saponins (ginsenoside-Rg2, Rg3, Rg5, and Rk1 etc.), as well as identifying the processing conditions which enable an enrichment in concentration of these compounds.

• Nutritional Sciences
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• 제9권4호
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• pp.240-247
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• 2006

In this study we investigated the neuroprotective, antioxidative, and hypocholestrolemic effects of dietary soy protein and soy isoflavone in a rat focal brain ischemia model. Weaning Sprague-Dawley rats were fed a 20% casein-based diet (CA), 20% soy protein-based diet (SP), or 0.2% soy isoflavones-supplemented diet (ISO) for 6 weeks. The cortical infarction volume of the ISO group was significantly lower than that of the SP group. The thiobarbituric acid reactive substances (TBARS) were considerably lower in the ISO group than the CA group. Glutatbione peroxidase activities of the SP group were notably higher than those of the CA group. Acetylcholinesterase (AchE) activities of the SP group were significantly decreased compared to the CA group. LDL cholesterol levels and LDL/HDL ratios of the ISO group were lower than those of the CA and SP groups. Our results collectively suggest that soy isoflavones may contribute to neuroprotection by reducing the TBARS and serum LDL/HDL ratio, whereas soy protein may be associated with the regulation of cognitive functions by modulating AchE activity.

• Journal of Cancer Prevention
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• 제21권3호
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• pp.135-143
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• 2016

Background: Fraxetin (7,8-dihydroxy-6-methoxy coumarin), a coumarin derivative, has been reported to possess antioxidative, anti-inflammatory and neuroprotective effects. A number of recent observations suggest that the induction of heme oxygenase-1 (HO-1) inhibits inflammation and tumorigenesis. In the present study, we determined the effect of fraxetin on HO-1 expression in HaCaT human keratinocytes and investigated its underlying molecular mechanisms. Methods: Reverse transcriptase-PCR and Western blot analysis were performed to detect HO-1 mRNA and protein expression, respectively. Cell viability was measured by the MTS test. The induction of intracellular reactive oxygen species (ROS) by fraxetin was evaluated by 2′,7′-dichlorofluorescin diacetate staining. Results: Fraxetin upregulated mRNA and protein expression of HO-1. Incubation with fraxetin induced the localization of nuclear factor-erythroid-2-related factor-2 (Nrf2) in the nucleus and increased the antioxidant response element-reporter gene activity. Fraxetin also induced the phosphorylation of Akt and AMP-activated protein kinase $(AMPK){\alpha}$ and diminished the expression of phosphatase and tensin homolog, a negative regulator of Akt. Pharmacological inhibition of Akt and $AMPK{\alpha}$ abrogated fraxetin-induced expression of HO-1 and nuclear localization of Nrf2. Furthermore, fraxetin generated ROS in a concentration-dependent manner. Conclusions: Fraxetin induces HO-1 expression through activation of Akt/Nrf2 or $AMPK{\alpha}/Nrf2$ pathway in HaCaT cells.

• 한국식생활문화학회지
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• 제36권6호
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• pp.633-639
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• 2021

Raphanus sativus var. hortensis f. raphanistroides Makino (Korean wild radish [WR]) are root vegetables belonging to the Brassicaceae family. These radish species mostly grow in sea areas in Asia, where they have been traditionally used as a medicinal food to treat various diseases. To investigate the effect of WR on neuronal cell death in SH-SY5Y cells, beta-amyloid was used to develop the cell death model. WR attenuated neuronal cell death in SH-SY5Y and regulated the mitogen-activated protein kinase (MAPK) signaling. WR extract also inhibited acetylcholinesterase inhibitor activity. Additionally, the WR treatment group ameliorated the behavior of the memory-impaired mice in a scopolamine-induced mouse model. In the behavior test, WR treated mice showed shorter escape latency and swimming distance and improved the platform-crossing number and the swimming time within the target quadrant. Furthermore, WR prevented histological loss of neurons in hippocampal CA1 regions induced by scopolamine. This study shows that WR can prevent memory impairment which may be a crucial way for the prevention and treatment of memory dysfunction and neuronal cell death.

• 한국식생활문화학회지
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• 제35권6호
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• pp.605-612
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• 2020

In this study, 11 plant extracts from Bangladesh were used to evaluate the total phenolic and flavonoid content, in vitro antioxidant activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzthiazolin-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assay. Also, the inhibitory effect of nitric oxide (NO) production in RAW 264.7 macrophage cell line and the neuroprotective effect on H2O2-induced PC12 cells were tested. Our results revealed that Piper betle L. showed the highest total phenolic content (162.2 mg GAE/g extract) among the 11 plants from Bangladesh. Most plants showed strong radical scavenging effects and ferric reducing antioxidant power. Besides, Piper betle L. protected PC12 neuronal cells against H2O2 related oxidative stress in LPS-induced PC12 cells. Regarding the anti-inflammatory effect, Piper betle L. significantly inhibited NO accumulation in LPS-induced RAW 264.7 cells. Our results provide evidence that Piper betle L. could be useful for the development of functional health foods.

• Journal of Applied Biological Chemistry
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• 제65권1호
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• pp.23-31
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• 2022

Oxidative stress and neuroinflammation play important roles in the pathogenesis of Alzheimer's disease (AD). This study investigated the protective effects of paeoniflorin (PF) against neuronal oxidative stress and neuroinflammation in lipopolysaccharide (LPS)-induced mice. The brains of LPS-injected control group showed significantly increased neuroinflammation by activating the nuclear factor kappa B (NF-κB) pathway and increasing inflammatory mediators. However, administration of PF significantly attenuated oxidative stress by inhibiting lipid peroxidation, nitric oxide levels, and reactive oxygen species production in the brain; PF at doses of 5 and 10 mg/kg/day downregulated the expression of NF-κB pathway-related proteins and significantly decreased inflammatory mediators including inducible nitric oxide synthase and cyclooxygenase-2. Moreover, the levels of brain-derived neurotrophic factor and its receptor, tropomycin receptor kinase B, were significantly increased in PF-treated mice. Furthermore, acetylcholinesterase activity and the ration of B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X were significantly reduced by PF in the brains of LPS-induced mice, resulting in the inhibition of cholinergic dysfunction and neuronal apoptosis. Thus, we can conclude that administration of PF to mice prevents the development of LPS-induced AD pathology through the inhibition of neuronal oxidative stress and neuroinflammation, suggesting that PF has a therapeutic potential for AD.