• Journal of Korean Neurosurgical Society
• /
• v.59 no.3
• /
• pp.259-268
• /
• 2016

Objective : Accumulation of advanced glycation end-products (AGE) and mitochondrial glycation is importantly implicated in the pathological changes of the brain associated with diabetic complications, Alzheimer disease, and aging. The present study was undertaken to determine whether sildenafil, a type 5 phosphodiesterase type (PDE-5) inhibitor, has beneficial effect on neuronal cells challenged with AGE-induced oxidative stress to preserve their mitochondrial functional integrity. Methods : HT-22 hippocampal neuronal cells were exposed to AGE and changes in the mitochondrial functional parameters were determined. Pretreatment of cells with sildenafil effectively ameliorated these AGE-induced deterioration of mitochondrial functional integrity. Results : AGE-treated cells lost their mitochondrial functional integrity which was estimated by their MTT reduction ability and intracellular ATP concentration. These cells exhibited stimulated generation of reactive oxygen species (ROS), disruption of mitochondrial membrane potential, induction of mitochondrial permeability transition, and release of the cytochrome C, activation of the caspase-3 accompanied by apoptosis. Western blot analyses and qRT-PCR demonstrated that sildenafil increased the expression level of the heme oxygenase-1 (HO-1). CoPP and bilirubin, an inducer of HO-1 and a metabolic product of HO-1, respectively, provided a similar protective effects. On the contrary, the HO-1 inhibitor ZnPP IX blocked the effect of sildenafil. Transfection with HO-1 siRNA significantly reduced the protective effect of sildenafil on the loss of MTT reduction ability and MPT induction in AGE-treated cells. Conclusion : Taken together, our results suggested that sildenafil provides beneficial effect to protect the HT-22 hippocampal neuronal cells against AGE-induced deterioration of mitochondrial integrity, and upregulation of HO-1 is involved in the underlying mechanism.

• The Korean Journal of Physiology and Pharmacology
• /
• v.17 no.4
• /
• pp.331-338
• /
• 2013

AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, is activated in response to cellular stress when intracellular levels of AMP increase. We investigated the neuroprotective effects of AMPK against scopolamine-induced memory impairment in vivo and glutamate-induced cytotoxicity in vitro. An adenovirus expressing AMPK wild type alpha subunit (WT) or a dominant negative form (DN) was injected into the hippocampus of rats using a stereotaxic apparatus. The AMPK WT-injected rats showed significant reversal of the scopolamine induced cognitive deficit as evaluated by escape latency in the Morris water maze. In addition, they showed enhanced acetylcholinesterase (AChE)-reactive neurons in the hippocampus, implying increased cholinergic activity in response to AMPK. We also studied the cellular mechanism by which AMPK protects against glutamate-induced cell death in primary cultured rat hippocampal neurons. We further demonstrated that AMPK WT-infected cells increased cell viability and reduced Annexin V positive hippocampal neurons. Western blot analysis indicated that AMPK WT-infected cells reduced the expression of Bax and had no effects on Bcl-2, which resulted in a decreased Bax/Bcl-2 ratio. These data suggest that AMPK is a useful cognitive impairment treatment target, and that its beneficial effects are mediated via the protective capacity of hippocampal neurons.

• Nutritional Sciences
• /
• v.9 no.1
• /
• pp.9-13
• /
• 2006

The differential effects of various fatty acids such as n-3 and n-6 types or degrees of unsaturation on the CYP2E1 induction and the production of lipid peroxidation (LPO) were investigated. The CYP2E1-transduced human hepatoma HepG2 cells (E47) were cultured in RPMI 1640 media containing different concentrations of various fatty acids up to 48 h incubation compared to 04 cells and CYP2E1-null cells. Treated fatty acids were linoleic acid (LA:n-6, C18:2), arachidonic acid (AA:n-6, C20:4) and docosahexaenoic acid (DHA:n-3, C22:6). The cell survival rate was decreased corresponding to the degree of unsaturation (LA>AA $\cong$DHA) and to LPO production in E47 and 04 cells. The four or five unsaturation degree of fatty acids, AA and DHA, caused time- and dose-dependent cell death in E47 cells but not as much as in C34 (without CYP2E1), suggesting an important role of CYP2E1 in the DHA mediated damage. In the levels of lipid peroxides (LPO), AA also elevated LPO by 3- and 5- fold compared to DHA or LA treated E47 cells. However, AA did not increase LPO until 48 h incubation in C34 cells. In conclusion, the polyunsaturated fatty acids induced CYP2E1 induction might be changed by the elevated levels of lipid peroxide (LPO) and oxidative stress through the connection of CYP2E1 and degrees of unsaturated fatty acids.

• Korean Journal of Medicinal Crop Science
• /
• v.15 no.5
• /
• pp.352-356
• /
• 2007

The present study was investigated the anti-oxidative effects of aloe vera ingestion on brain and kidney in aged rats by monitoring several oxidative-related parameters. Male specific pathogen-free Fischer 344 rats were randomly divided into four groups of five rat each: Group A was fed test chow without aloe supplementation; Group B was fed a diet containing a 1% freeze-dried aloe filet; Group C was fed a diet containing a 1% charcoal-processed, freeze-dried aloe filet; and Group D was fed a diet containing a charcoal-processed, freeze-dried, whole leaf aloe in drinking water. Analyses of tissues were done at 4 months and 16 months of age. Results showed that a long-term intake of aloe, regardless of the preparation used, enhanced antioxidant defenses against lipid peroxidation, as indicated by reduced phosphatidylcholine hydroperoxide levels in both brain and kidney. The additional benefit of aloe intake on the anti-oxidative action was evidenced by enhanced superoxide dismutase and catalase activity in all aloe-ingested groups. Another beneficial effect of aloe shown in this study, although not an anti-oxidative parameter, was its cholesterol-lowering effect as detected in brain and kidney with significant decreases at age16 months of aloe-fed rats. Based on these findings, we conclude that a long-term dietary aloe supplementation modulated the anti-oxidative defense systems and cholesterol level.

• Tuberculosis and Respiratory Diseases
• /
• v.71 no.2
• /
• pp.97-105
• /
• 2011

Background: It was hypothesized that the immunomodulating effects of moxifloxacin contribute to ameliorate oleic acid (OA)-induced acute lung injury (ALI) by suppression of cytosolic phospholipase A2 (cPLA2). This was based on observations from experiments on rats associated with neutrophilic respiratory burst, cPLA2 activity, and expressions of cPLA2, $TNF{\alpha}$, and COX-II in the lung. Methods: ALI was induced by intravenous injection of OA in male Sprague-Dawley rats. Five hours after OA injection, protein content in bronchoalveolar lavage (BAL), lung myeloperoxidase (MPO) activity, and numbers of BAL neutrophils were measured. As an index of oxidative stress-induced lung injury, the content of malondialdehyde (MDA) in lung tissues was also determined. Lung histology, immunohistochemistry and determination of activity of cPLA2 in lung tissues were carried out. In addition, Western blotting of $TNF{\alpha}$ and COX-II in lung tissues was performed. Results: The accumulation of neutrophils in the lungs was observed after OA injection. BAL protein was increased along with neutrophilic infiltration and migration by OA. Moxifloxacin decreased all of these parameters of ALI and ameliorated ALI histologically. The increased malondialdehyde (MDA) in the lung by OA was also decreased by moxifloxacin. Moxifloxacin not only suppressed cPLA2 expression in the lungs and neutrophils but also decreased cPLA2 activity in lung tissues of rats given OA. The enhanced expressions of $TNF{\alpha}$ and COX-2 in the lung tissues of rats given OA were also suppressed by moxifloxacin. Conclusion: Moxifloxacin inhibited cPLA2 and down-regulated $TNF{\alpha}$ and COX-2 in the lungs of rats given OA, which resulted in the attenuation of inflammatory lung injury.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.23 no.4
• /
• pp.853-859
• /
• 2009

Nardostachys chinensis has been used widely as a traditional medicine for the treatment of diverse diseases. The dried plant was extracted with 85% methanol extract (NC). We investigated the antioxidant properties of NC on the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical, superoxide anion and nitric oxide radical scavenging capacity under in vitro assays. NC showed potent antioxidant activity, compared to ascorbic acid. In macrophages, nitric oxide is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions in inflammation. In the present study, it was also investigated that the inhibition effects on NO and the mechanism of down-regulation of immune response by NC in IFN-IFN-$\gamma$/LPS-stimulated mouse (C57BL/6) peritoneal macrophages. Extracts of NC suppressed NO production and the expression of iNOS and COX-2. The present results indicate that NC has an antioxidant and anti-inflammatory properties and therefore may be beneficial in diseases which related to oxidative stress-mediated chronic inflammatory disorders.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.34 no.2
• /
• pp.81-87
• /
• 2020

Cognitive impairment is symptoms of dementia, a degenerative brain disease that is drawing attention in a rapidly aging society. This study was conducted to investigate the improvement of cognitive function of Leonurus japonicus on scopolamine-induced memory impairment in mice and the effect and mechanism of memory recovery. In vivo studies were conducted on mice orally pretreated with L. japonicus in doses of 50, 100 and 200 mg/kg (p.o.) and scopolamine (1 mg/kg, i.p.) were injected 30 min before the behavioral task. Antioxidant activity was assessed by 2,2-diphenyl-1-picryl hydrazyl (DPPH) assay and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, and acetylcholinesterase (AChE) inhibition activity evaluated by Ellman's method. In behavior studies showed that L. japonicus has an improved the memory of scopolamine-treated mice in Y-maze, passive avoidance and Morris water maze test. In addition, L. japonicus was also exerted free radical scavenging activity and inhibited acetyl cholinesterase activity. These results suggest that L. japonicus improves short-term and long-term memory in scopolamine-induced memory decline model and prevents scopolamine-induced memory impairments through in reduced oxidative stress and acetyl cholinesterase inhibition effect. Thus, L. japonicus is related to functional medicinal materials for prevention and treatment of human dementia patients.

• Journal of Life Science
• /
• v.21 no.8
• /
• pp.1100-1108
• /
• 2011

The immunomodulating effects of moxifloxacin seem to be effective in downregulating inflammatory reactions. This presumed effect was tested in endotoxin (ETX)-induced acute lung injury (ALI) in rats. After moxifloxacin treatment (10 mg/kg) of ETX-given rats, lung myeloperoxidase (MPO) activity, bronchoalveolar-lavage (BAL) protein, and the number of neutrophils in the BAL cells were measured. Light and electron microscopic structures were also examined. Electron microscopic $CeCl_3$ histochemistry for the detection of hydrogen peroxide in the lungs and immunohistochemistry of cytosolic phospholipase A2 (cPLA2) in the lung tissues and BAL cells were performed. To examine the expression of TNF${\alpha}$ in the lungs, western blotting was carried out with the lung tissues. ETX had accumulated neutrophils in the lungs, which was followed by lung leak. Oxidative stress occurred, and increased expression of cPLA2 in the lung tissues and BAL cells was observed in the ETX-given rats. Simultaneously, the expression of TNF${\alpha}$ was enhanced by ETX. Moxifloxacin, however, decreased all these parameters, indicating that ALI may have been ameliorated. Moxifloxacin appears to ameliorate ETX-induced ALI partially through the suppression of cPLA2 in the lungs of rats.

• Food Science and Biotechnology
• /
• v.15 no.2
• /
• pp.270-276
• /
• 2006

We evaluated the effects of extracts of Tsunokaori tangor peel on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in RAW 264.7 cells. The ethyl acetate fraction of Tsunokaori tangor peel (EA-TTP) markedly inhibited the production of NO and $PGE_2$ in LPS-stimulated RAW 264.7 cells. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins were down-regulated in a dose-dependent manner. Additionally, EA-TTP decreased the expression iNOS mRNA but not COX-2 mRNA. To determine the upstream signaling mechanism for the down-regulation of LPS-induced iNOS expression, we investigated the effect of EA-TTP on the degradation and re-synthesis of $I{\kappa}B{\alpha}$. EA-TTP dose-dependently delayed $I{\kappa}B{\alpha}$ degradation and increased $I{\kappa}B{\alpha}$ re-appearance following degradation, suggesting this as the mechanism by which EA-TTP suppressed iNOS gene expression. The EA-TTP also dose-dependently reduced the expression of the cellular stress-response protein heme oxygenase-1, and inhibited the LPS-induced sustained activation of extracellar signal-regulated kinase (ERK).

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.15
• /
• pp.6527-6534
• /
• 2015

Background: In Japan, in comparison with the rest of the world the death rate of lung cancer is low although the smoking rate is relatively high. This is the so-called "Japanese smoking paradox". A healthy diet is proposed to attenuate the risk without quitting smoking. We here examined the relationships between smoking status (SS) and the consumption of food and nutrient in Japan. Materials and Methods: Totals of 5,587 men and 2,718 women were divided into three (non-smokers, smokers and heavy smokers) and two (non-smokers and smokers) groups, respectively, according to pack-year, which represents the amount of smoking over a long period. Food and nutrient consumption was estimated with a validated food frequency questionnaire. Using general linear models, food and nutrient consumption was estimated for each group in men and women, separately. Results: In men, SS was positively related to consumption of rice, 3 alcoholic beverages, carbohydrate, alcohol and other 8 foods/nutrients (p< 0.05 for all) and negatively to those of protein animal, fat, fatty acids, dietary fiber, isoflavones and 36 other foods/nutrients (p<0.05 for all). In women, SS was positively associated with intake of 13 foods/nutrients, while being negatively associated with those of rice, energy, dietary fiber, and 14 other foods/nutrients (p<0.05 for all). Conclusions: Our results support lower intake of vegetables and fruits rich in antioxidants, which are thought as preventive factors for many diseases, in smokers.