Oxidative stress or the accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. The expression of HO-1 has cytoprotective effects in glutamate-induced oxidative cytotoxicity in HT22 cells. The induction of HO-1 is primarily regulated at the transcriptional level, and its induction by various inducers is related to the nuclear transcription factor-E2-related factor 2 (Nrf2). Nrf2 is a master regulator of the antioxidant response. NNMBS008, the water-insoluble fraction of the 70% EtOH extract of roots of Sophora flavescens, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS008 makes the nuclear accumulation of Nrf2 pathway. In conclusion, the waterinsoluble fraction of the 70% EtOH extract of roots of S. flavescens (NNMBS008) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 pathway in mouse hippocampal HT22 cells. These results suggest that these extracts could be the effective candidates for the treatment of ROS-related neurological diseases.
Objectives: Activated microglia cells play an important role in inflammatory responses in the central nervous system (CNS) which are involved in neurodegenerative diseases. We attempted to determine the anti-inflammatory effects of Cheongnoimyungshin-hwan (CNMSH) in microglia cells. Methods: We examined the effect of CNMSH on the inflammatory responses in BV2 microglia cells induced by lipopolysaccharide (LPS) and explored the mechanism underlying the action of CNMSH. Results: BV2 cells treated with LPS showed an up-regulation of nitric oxide (NO), prostaglandin $PGE_2(PGE_2)$ and interleukin $1{\beta}(IL-1{\beta})$ release, whereas CNMSH suppressed this up-regulation. CNMSH inhibited the induction of COX-2, iNOS and $IL-1{\beta}$ proteins in LPS-treated BV2 cells and blocked the LPS-induced phosphorylation and nuclear translocation of nuclear factor ${\kappa}B(NF-{\kappa}B$). Furthermore, CNMSH attenuated the LPS-induced phosphorylation of extracellular signal-regulated kinase and p38 mitogen activated protein kinase (MAPK), as well as the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, but did not inhibit the LPS-induced phosphorylation of c-Jun amino terminal kinase. Conclusions: These results suggest that the inhibitory effect of CNMSH on the LPS-induced production of inflammatory mediators and cytokines in BV2 cells is associated with the suppression of the $NF-{\kappa}B$ and PI3KAkt signaling pathways.
Kim, Seong-Il;Raffi Mikaelian;Kwak, Jin-Hwan;Kim, In-Chull;Lee, Chang-Ho
Biomolecules & Therapeutics
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v.3
no.4
/
pp.316-321
/
1995
All the pharmacological studies of LB17522 described here were carried out with high doses (fifteen to sixty times of the therapeutic dose) to determine an indication of potential side effects in clinical use in terms of the acute clinical signs, cardiovascular and central nervous system. LB10522 does not produce any observable clinical signs except for the symptoms such as moist eye, skin rash, slight salivation, vomitting, and slightly reduced activity. The effects of LB10522 on the hemodynamics and cardiac function of anesthetized beagle dogs are as follows; heart rates and mean arterial blood pressure had a tendency to increase mildly, which is a normal finding in anesthetized dogs. All the animals except for one showed relatively stable respiratory rates throughout the observation period. Each animal treated with LB10522 showed slight increase in the left cardiac work and left ventricular stroke work which are mainly related to corresponding increases in cardiac output. Femoral blood flow were shown to be increased in some animals treated with LB10522. The epileptogenic activities of various cephalosporins were assessed by a direct intracerebral injection of appropriate concentration of test articles. The CD$_{50}$ values (nmol) obtained from the analysis of the dose-response data are as follows; 78.2, 175.3, 156.3, and 53.5 for cefazolin, cephaloridine, ceftazidime, and LB 10522, respectively. LB10522 seems to be equipotent with cefazolin or to be three times more potent than cephaloridine and ceftazidime in causing adverse CNS stimulation. Taken into consideration all the information obtained, LB10522 is not supposed to induce much changes in the functions examined in these studies in man at therapeutic doses.s.
Since the wide spread application of hyperbaric oxygenation in clinical setting, the problems of oxygen toxicity have been attracting a deep interest from the researchers on hyperbaric medicine as a practical issue. Among extensive research trials, the study on the protective agents against oxygen toxicity occupied one of the most challenging field. As the mechanisms of oxygen toxicity, the role of the oxygen free radicals produced by peroxidation process are strongly accepted by the leading researchers on oxygen toxicity, the probable protective effects of antioxidant against oxygen toxicity are sustaining a sufficient rationale. In this study, the author attempted to evaluate the effect of vitamin E as a protective agent against oxygen toxicity through the observation of death rate, convulsion rate, time to convulsion, and macroscopic and microscopic pathological changes of experimental rats exposed to 100% oxygen at 5 ATA for 120 minutes. The findings observed are as follows: 1) The death rate, convulsion rate, time to convulsion, organ/body weight ratio and microscopic pathological findings were identified as reliable objective and quantitative indices for oxygen toxicity. 2) Vitamin E showed excellent protective effects against CNS and pulmonary oxygen toxicity as a strong antioxidant. The most effective dose seemed to be around 400 mg/kg 3) The results of this study are supporting the oxygen free radical hypothesis on oxygen toxicity.
Endogenous carbon monoxide (CO) shares with nitric oxide (NO) a role as a putative neural messenger in the brain. Both gases are believed to modulate CNS function via an increase in cytoplasmic cGMP concentrations secondary to the activation of soluble guanylate cyclase (sGC). Recently CO and NO were proposed as a possible mediator of febrile response in hypothalamus. NO has been reported to activate both the constitutive and inducible isoform of the cyclooxygenase (COX). Thus, we investigated whether CO arising from heme catabolism by heme oxygenate (HO) is involved in the febrile response via the activation of COX in the hypothalamus. $PGE_2$ which is a final mediator of febrile response released from primary cultured hypothalamic cells was taken as a marker of COX activity. $PGE_2$ concentration was measured with EIA kits. Exogenous CO (CO-saturated medium) and hemin (a substrate and potent inducer of HO) evoked an increase in $PGE_2$ release from hypothalamic cells, and these effects were blocked by methylene blue (an inhibitor of sGC). And membrane permeable cGMP analogue, dibutyryl-cGMP elicited significant increases in $PGE_2$release. These results suggest that there may be a functional link between HO and COX enzymatic activities. The gaseous product of hemin through the HO pathway, CO, might play a role through the modulation of the COX activity in the hypothalamus.
We have already known, neural progenitor cells exist not only in the developing brain, but in certain spots in adult CNS in mammals, so it will be of great value to find out some compounds which can interfere these cells proliferation ability. In this research, we observed that ginsenoside $Rg_1$ can not only enhance neural progenitors' proliferation ability in vitro, but increase neurogenesis in adult mouse dentate gyrus in vivo. Firstly, we set up neural progenitor cells' culture system from embryonic rats' hippocampus and prove their feature through immunocytochemistry. Then by using MTT assay, we found that when growing with ginsenoside $Rg_1(0.5\~2.5{\mu}mol/l)$, the progenitor cells' survival rate nearly doubled, furthermore, we proved that this increase was due to the increment of cell proliferation through $^3H-thimidine$ incorporation assay, hence, we drew the first conclusion: ginsenoside Rg1 has the ability to stimulate neural progenitor cells' proliferation in vitro; in order to observe this compound's effect in vivo, we devised the following experiment: after administering ginsenoside Rg1 (5, 10 mg/kg, once a day) intraperitoneally for two weeks, we examine the number of BrdU positive cells in the dentate gyrus of mice, and found that Rg1 could increase the number of proliferation cells significantly in vivo. From these studies, we are quite sure about Rg1's effects on the proliferation ability of neural progenitor cells both in vitro and in vivo, certain targets of the compound and its underlying mechanisms are in progress.
Objectives: Pastinaca sativa (parsnip), is a plant with nutritional and medicinal properties which has been used in all over the world and study about it is rare. In Persian Medicine parsnip is named as zardak and has many uses such as laxative, libido enhancer, kidney stone crusher and diuretic. Because the wide traditional usage of parsnip, in this review the composition and pharmacological properties of this plant are discussed. Methods: Some data base such as Cochrane, Scopus, PubMed were searched up to 2018 for studies about Pastinaca sativa. In this review study after consider to exclusion criteria, all of the English review and clinical trial were included. Results: Finally, 46 articles were selected for extraction data about the parsnip. Data extraction based on these studies the most important active ingredients of parsnip include coumarins, furanocoumarins, polyacetylenes, essential oils and flavonoids. Different studies determined that Pastinaca sativa has pharmacological effects in CNS, respiratory, gastrointestinal, liver, skin, cardiovascular and urogenital diseases. Conclusion: The most important active ingredients in Pastinaca sativa are furanocoumarins, flavonoids and polyacetylenes, and it has many pharmacological properties, including anti-inflammatory, antispasmodic, vasodilator, antifungal, antimicrobial and antidepressant. A main mentioned side effect of parsnip is phototoxicity that was usually reported in direct skin contact. However, family and Some properties and compounds of Pastinaca sativa and Daucus carota are similar but carrots are very popular nowadays. Due to abundant active components and few clinical studies of parsnip, more Studies are recommended to evaluate the effects of it.
Seon Ah Park;Thao Thi Phuong Nguyen;Soo Joung Park;Seong Kyu Han
The Korean Journal of Physiology and Pharmacology
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v.28
no.1
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pp.73-81
/
2024
The substantia gelatinosa (SG) within the trigeminal subnucleus caudalis (Vc) is recognized as a pivotal site of integrating and modulating afferent fibers carrying orofacial nociceptive information. Although naringenin (4',5,7-thrihydroxyflavanone), a natural bioflavonoid, has been proven to possess various biological effects in the central nervous system (CNS), the activity of naringenin at the orofacial nociceptive site has not been reported yet. In this study, we explored the influence of naringenin on GABA response in SG neurons of Vc using whole-cell patch-clamp technique. The application of GABA in a bath induced two forms of GABA responses: slow and fast. Naringenin enhanced both amplitude and area under curve (AUC) of GABA-mediated responses in 57% (12/21) of tested neurons while decreasing both parameters in 33% (7/21) of neurons. The enhancing or suppressing effect of naringenin on GABA response have been observed, with enhancement occurring when the GABA response was slow, and suppression when it was fast. Furthermore, both the enhancement of slower GABA responses and the suppression of faster GABA responses by naringenin were concentration dependent. Interestingly, the nature of GABA response was also found to be sex-dependent. A majority of SG neurons from juvenile female mice exhibited slower GABA responses, whereas those from juvenile males predominantly displayed faster GABA responses. Taken together, this study indicates that naringenin plays a partial role in modulating orofacial nociception and may hold promise as a therapeutic target for treating orofacial pain, with effects that vary according to sex.
Journal of the Korea Academia-Industrial cooperation Society
/
v.17
no.4
/
pp.74-84
/
2016
Open Source Software (OSS) is a new paradigm for software development. The system is based on the notion of giving software (including sources) away for free, and making money on services, customizing and maintenance. For these reasons, many software companies have considered adopting and using OSS in Software R&D. A variety of factors may influence the use of decision making of OSS. The objective of this study was to explore the significant factors affecting the use decision of OSS and the job performance of OSS usage in software R&D. A research model was suggested based on the TOE Framework and Information Systems Success Model. These findings show that technical benefits of OSS have significant effects on OSS use. The technical benefits of OSS, and organization context, in turn, have significant effects on the use of OSS. On the other hand, the technical risks of OSS and the environment context have no effects on OSS use. In addition, OSS use and user satisfaction have significant effects on the individual job performance. This research contributes towards advancing the theoretical understanding of the OSS Benefits and Performance in Software Development.
A prevalence study was carried out on 847 CMD patients who had visited the Department of Oral Medicine in Pusan National University from 1990 to 1993. To obtain the same type of information, all subjects were interviewed and examined clinically using a standardized examination form, The ratio of women to men was about 3:1 and all subjects were divided into acute and chronic groups on the basis of 6 months of duration. Diagnostic groups consisted of muscle disorder, joint disorder and muscle-joint disorder. As related to gender, duration and diagnosis subjective and objective symptoms in CMD were studied. The obtained results were as follows : 1. Muscle-joint disorder had the highest percent, followed by muscle disorder and joint disorder. 2. The most common reasons for CMD treatment were pain, joint noise and limited opening, while headache and neckache were relatively often reported as associated symptoms and dizziness, ringing in the ears also reported as secondary CNS excitatory effects. 3. Pain was more ofter seen in women, acute group and muscle-related disorder groups (p<0.05, p<0.01). Noise was significantly frequent in chronic group and joint-related groups (p<0.01). 4. Analysis of contributing factors presented that macrotrauma was found frequently in men (p<0.05), and that muscle-related groups were more related to stress than joint disorder grop (p<0.05). 5. Hard end feel was seen significantly often in joint-related disorder group (p<0.05). On the other hand, soft end feel was frequent in muscle disorder. 6. Reciprocal clicks and crepitation increased with chronicity. Subjects with joint-related disorder groups significantly often reported all kinds of noises (p<0.01). 7. Tender muscles and joints were more often reported in women and chronic group. Whereas muscle-related disorder groups revealed significantly more tender muscles (p<0.01). joint-related disorder groups presented significantly more tender joints (p<0.01).
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