• 사상체질의학회지
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• 제16권1호
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• pp.120-129
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• 2004

Yangkyuk-Sanhwa-Tang(YST) has been widely used as a formula for the Soyangin cerebral infarction (CI) patients according to Sasang constitutional philosophy. Brain cells produce cytokines and chemokines during the inflammatory process after stroke both in animal models and in patients. Previously, regulation of serum cytokine levels by YSThas been observed in individuals at the acute stage of CI disease, but there have not been other scientific investigations on YST. The author investigated the effect of YST on theproduction of various cytokines using peripheral blood mononuclear cells (PBMCs)from the Soyangin (CI) patients, and Soyangin normal group. The cytokine production was analyzed using enzyme-linked immunosorbent assay (ELISA). The amount of interleukin (IL)-1, IL-1, IL-6, IL-8, and tumor necrosis factor (TNF)- in culture supernatant significantly increased in the LPS-treated cells compared with unstimulated-cells (P < 0.05). However, in LPS-stimulated PBMCs, cytokines level in CI patients group was higher than that of normal group. YST (1 mg/ml) significantly inhibited IL-1, IL-1, and IL-8 production in PBMCs stimulated with LPS (about 85% for IL-1, 87% for IL-1, and 53% for IL-8, P < 0.05), but did not significantly inhibit IL-6 and TNF- production in the CI patients group. We also show that YST significantly increased LPS-induced IL-1, IL-6, and TNF- production in the normal group. Thesedata suggest that YST has a regulatoryeffect on the cytokine production, which might explain its beneficial effect in the treatment of CI.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.627-633
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• 2015

Background: To study the effect of parecoxib, a novel cyclooxygenase-2 selective inhibitor, on the radiation response of colorectal cancer (CRC) cells and its underlying mechanisms. Materials and Methods: Both in vitro colony formation and apoptosis assays as well as in vivo mouse xenograft experiments were used to explore the radiosensitizing effects of parecoxib in human HCT116 and HT29 CRC cells. Results: Parecoxib sensitized CRC cells to radiation in vitro with a sensitivity enhancement ratio of 1.32 for HCT116 cells and 1.15 for HT29 cells at a surviving fraction of 0.37. This effect was partially attributable to enhanced apoptosis induction by parecoxib combined with radiation, as illustrated using an in vitro apoptosis assays. Parecoxib augmented the tumor response of HCT116 xenografts to radiation, achieving growth delay more than 20 days and an enhancement factor of 1.53. In accordance with the in vitro results, parecoxib combined with radiation resulted in less proliferation and more apoptosis in tumors than radiation alone. Radiation monotherapy decreased microvessel density (MVD) and microvessel intensity (MVI), but increased the hypoxia level in xenografts. Parecoxib did not affect MVD, but it increased MVI and attenuated hypoxia. Conclusions: Parecoxib can effectively enhance radiation sensitivity in CRC cells through direct effects on tumor cells and indirect effects on tumor vasculature.

• IMMUNE NETWORK
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• 제3권4호
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• pp.310-319
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• 2003

Inflammatory mediators has been recognized as an important role in the pathogenesis of rheumatoid arthritis (RA). IL-17 is increasingly recognized as an important regulator of immune and inflammatory responses, including induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence of the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. However, the signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in the regulation of IL-17 production in RA. PBMC were separated from RA (n=24) patients, and stimulated with various agents (anti CD3, anti CD28, PHA, ConA, IL-15). IL-17 levels were determined by sandwich ELISA and RT-PCR. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody, PHA, IL-15 or MCP-1 (P<0.05). ConA also strongly induced IL-17 production (P<0.001), whereas TNF-alpha, IL-1beta, IL-18 or TGF-beta did not. IL-17 was detected in the PBMC of patients with osteoarthritis (OA) but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K-Akt pathway and activation of the PI3K-Akt pathway resulted in a pronounced augmentation of nuclear factor kappaB ($NF-{\kappa}B$). IL-17 production by activated PBMC in RA is completely or partially blocked in the presence of $NF-{\kappa}B$ inhibitor PDTC and PI3K-Akt inhibitor, wortmannin and LY294002, respectively. Whereas the inhibition of AP-1 and extracellular signal-regulated kinase (ERK)1/2 did not affect IL-17 production. These results provide new insight into that PI3K/Akt and $NF-{\kappa}B$ dependent signal transduction pathway could be involved in the overproduction of key inflammatory cytokine, IL-17 in rheumatoid arthritis.

• Advances in Traditional Medicine
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• 제8권4호
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• pp.430-439
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• 2008

Chungpaesagan-tang (CPSGT) is most frequently used to treat ischemic brain injury in tradition Korean medicine. Clinically, cerebral ischemia is likely to be accompanied by preexisting or complicating disease. However, animal models used to examine the effects of herbal medicines on cerebral ischemia have not given this issue sufficient consideration. The present study was undertaken to determine the effects of CPSGT on focal cerebral ischemia in normal and SHR rats subjected to transient middle cerebral artery occlusion (MCAO). Animals were divided into four groups: Normal (Sprague-Dawley) rats subjected to MACO (the NC+MCAO group), normal rats subjected to MCAO and then administered CPSGT (NC + MCAO + CP), SHR rats subjected to MCAO (SHR + MCAO), and SHR rats subjected to MCAO and then administered CPSGT (SHR + MCAO + CP). MCAO was performed using the intraluminal method. CPSGT was administrated orally twice (1 and 4 h) after MCAO. All animals were sacrificed at 24 h postoperatively. Brain tissues were stained with hematoxylin & eosin, to examine the effect of CPSGT on ischemic brain tissues. In addition, changes in TNF-$\alpha$ expression in ischemic areas were examined by immunostaining. CPSGT was found to significantly reduce infarction areas in normal and SHR rats and infarction volumes in SHR rats. Similarly, CPGST markedly increased neuron numbers and sizes in all treated groups, except cell sizes in SHRs. Furthermore, CPSGT reduced TNF-$\alpha$ expression in MCAO administered SHR rats. The findings of the present study suggest that CPSGT effectively ameliorates neuron damage caused by MACO-induced cerebral ischemia, and that it has a significant neuroprotective effect after cerebral ischemia in SHR.

• Clinical and Experimental Pediatrics
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• 제53권10호
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• pp.898-908
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• 2010

Purpose: The neuroprotective effects of erythropoietin (EPO) have been recently shown in many animal models of brain injury, including hypoxic-ischemic (HI) encephalopathy, trauma, and excitotoxicity; however, limited data are available for such effects during the neonatal periods. Therefore, we investigated whether recombinant human EPO (rHuEPO) can protect against perinatal HI brain injury via an antiapoptotic mechanism. Methods: The left carotid artery was ligated in 7-day-old Sprague-Dawley (SD) rat pups ($in$ $vivo$ model). The animals were divided into 6 groups: normoxia control (NC), normoxia sham-operated (NS), hypoxia only (H), hypoxia+vehicle (HV), hypoxia+rHuEPO before a hypoxic insult (HE-B), and hypoxia+rHuEPO after a hypoxic insult (HE-A). Embryonic cortical neuronal cell culture of SD rats at 18 days gestation ($in$ $vitro$ model) was performed. The cultured cells were divided into 5 groups: normoxia (N), hypoxia (H), and 1, 10, and 100 IU/mL rHuEPO-treated groups. Results: In the $in$ $vivo$ model, Bcl-2 expressions in the H and HV groups were lower than those in the NC and NS groups, whereas those in the HE-A and HE-B groups were greater than those of the H and HV groups. The expressions of Bax and caspase-3 and the ratio of Bax/Bcl-2 were in contrast to those of Bcl-2. In the $in$ $vitro$ model, the patterns of Bcl-2, Bax, and caspase-3 expression and Bax/Bcl-2 ratio were similar to the results obtained in the in vivo model. Conclusion: rHuEPO exerts neuroprotective effect against perinatal HI brain injury via an antiapoptotic mechanism.

• 대한한방내과학회지
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• 제25권3호
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• pp.461-472
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• 2004

Objectives : For the screening of neuroprotective effects of medicinal herbs, the complex system of animal models suffer some disadvantages in controlling critical parameters such as blood pressure and body temperature. Additionally, application of drugs to the appropriate brain area sometimes is difficult, due to poor permeability though the blood brain barrier, and so potential protective effects might be masked. Methods : Organotypic hippocampal slice culture (OHSC) method has the advantages of being relatively easy to prepare and of maintaining the general structure, including tissue integrity and the connections between cells. Drugs can easily be applied and neuronal damage can easily be quantified by using tissues and culture media. This study demonstrates neuroprotective effects of Puerariae radix (葛根, PR), Salviae miltiorrhizae radix (丹蔘, SR), Rhei rhizoma (大黃, RR), and Bupleuri radix (柴胡, BR). These were screenedand compared to MK-801, antagonist of NMDA receptors, by using OHSC of 1 week-old Sprague-Dawley rats. Oxygen/glucose deprivation (OGD) were conducted in an anaerobic chamber $(85%\;N_2,\;10%\;CO_2\;and\;5%\;H_2)$ in a deoxygenated glucose-free medium for 60 minutes. Water extracts of each herbs were treated to culture media with $5\;{\mu}g/ml$ for 48 hours. Results : Neuronal cell death in the cultures was monitored by densitometric measurements of the cellular uptake of propidium iodide (PI). PI fluorescence images were obtained at 48 hours after the OGD and medicinal herb treatment. Also TUNEL-positive cells in the CAI and DG regions and LDH concentrations in culture media were measured at 48 hours after the OGD. According to measured data, MK-801, PR, SR and BR demonstrated significant neuroprotective effect against excessive neuronal cell death and apoptosis induced by the OGD insult. Especially, PR revealed similar neuroprotective effect to MK-801 and RR demonstrated weak neuroprotective effect. Conclusions : These results suggest that OHSC can be a suitable method for screening of neuroprotective effects of medicinal herbs. (This work was supported by the research program of Dongguk University and Grant 01-PJ9-PG1-01CO03-0003 from Ministry of Health & Welfare.)

• 동의신경정신과학회지
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• 제23권1호
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• pp.93-114
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• 2012

Objective : This study aimed to review the performance of traditional herbal prescriptions for treating dementia and present a strategy for research on dementia therapy utilizing herbal medicine. Methods : A definition was made to clarify the technology regarding the development of herbal prescriptions for treating dementia. The queries were compounded based on the initial keywords provided by experts in the field, then applied to the Web of Science database search engines from January 1986 to September 2011 to search related scientific articles. Before performing the analysis, papers were extracted from the initial search reviewed by experts and 80 articles were selected. Then, the selected papers were analyzed in terms of publish year, country, and type of herbal prescriptions. Furthermore, the research performance evaluation for treating dementia by herbal prescriptions was also created in terms of country and organization based on forward citation analysis. In addition to, for the evaluation regarding research quality, we classified and reviewed papers into two types: clinical studies and experimental studies. Results : According to the quantitative information analysis of 80 articles, the number of papers has increased by 21.9% per the yearly mean from 1995, and Japan had the largest portion within this research field. There were 34 kinds of traditional herbal prescriptions, among them Ukgansan had the highest number of studies followed by Jodeungsan, Dangkisoosan and so on. In addition, quality index as calculated by cites per paper is higher than average in Switzerland, Turkey and Japan. In the view of the evaluation on quality there were 12 clinical studies, 8 RCT reported that herbal prescriptions had efficacy at cognition, behavioral & psychological symptoms (BPSD) and activity of daily life (ADL) in various type of dementia. In experimental studies most of the studies were performed using animal models. The studies using Ukgansan were aimed at improving BPSD. The papers studied with Jodeungsan and Dangkisoosan targeted vascular dementia. Conclusions : In this study, research to develop traditional herbal prescriptions for treating dementia has the potential to improve symptoms since herbal medicines work as both multi-function and multi-target in dementia with multiple pathological or neurotoxic pathways. Therefore, the results of the research should be used in order to establish strategies to develop technology for treating dementia with traditional herbal prescriptions in the future.

• 동의신경정신과학회지
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• 제21권2호
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• pp.125-140
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• 2010

Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.

• 동의생리병리학회지
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• 제23권2호
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• pp.325-330
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• 2009

In Korea, medical diagnostic equipments and biochemical examination can not be used in order for diagnosing sub-healthy state or ante-disease state in oriental medicine clinic. So morphic analogical method used in oriental medicine can be a good tool as a disease-predictable signs in order to enable preventive diagnosis and therapy. Therefore the four geometrical subjects; Essence, Pneuma, Spirit, Blood(四科;精氣紳血) and the four taxonomical species; Pisces, Quadruped, Aves, Carapaces(四類;魚走鳥甲) are chosen as morphic models in this paper. The differences of two classifying methods with four subjects and four species were as follows. The diagnostic category was meta-medical and synthetic against medical specific. The diagnostic object was body in contrast with face. They were able to be applicant in psychology and classification of characteristics against diagnostics and therapeutics directly in oriental medicine. The theoretical basis was basic diagrams of four unit-fluids of body and morphological analogy with four animal species respectively. And the therapeutic aims were systemic pathogenesis following five phase theory against congestion and deficiency of Essence, Pneuma, Spirit, Blood. The four subjects and four species are mixed each other practically in clinic. But it should be used limitedly because of the above reasons described and must divide the principal and secondary factors and follow the pathology of principal shape factor. In order to improve the diagnostic value of ante-disease state, the discriminable standards, measurement methods, limit of interrelating interpretation and the criteria of abnormal disproportion were needed to be defined more clearly in advance.

• Journal of Ginseng Research
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• 제40권2호
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• pp.185-195
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• 2016

Background: To investigate the effect of pectinase-treated Panax ginseng (GINST) in cellular and male subfertility animal models. Methods: Hydrogen peroxide ($H_2O_2$)-induced mouse spermatocyte GC-2spd cells were used as an in vitro model. Cell viability was measured using MTT assay. For the in vivo study, GINST (200 mg/kg) mixed with a regular pellet diet was administered orally for 4 mo, and the changes in the mRNA and protein expression level of antioxidative and spermatogenic genes in young and aged control rats were compared using real-time reverse transcription polymerase chain reaction and western blotting. Results: GINST treatment ($50{\mu}g/mL$, $100{\mu}g/mL$, and $200{\mu}g/mL$) significantly (p < 0.05) inhibited the $H_2O_2$-induced ($200{\mu}M$) cytotoxicity in GC-2spd cells. Furthermore, GINST ($50{\mu}g/mL$ and $100{\mu}g/mL$) significantly (p < 0.05) ameliorated the $H_2O_2$-induced decrease in the expression level of antioxidant enzymes (peroxiredoxin 3 and 4, glutathione S-transferase m5, and glutathione peroxidase 4), spermatogenesis-related protein such as inhibin-${\alpha}$, and specific sex hormone receptors (androgen receptor, luteinizing hormone receptor, and follicle-stimulating hormone receptor) in GC-2spd cells. Similarly, the altered expression level of the above mentioned genes and of spermatogenesis-related nectin-2 and cAMP response element-binding protein in aged rat testes was ameliorated with GINST (200 mg/kg) treatment. Taken together, GINST attenuated $H_2O_2$-induced oxidative stress in GC-2 cells and modulated the expression of antioxidant-related genes and of spermatogenic-related proteins and sex hormone receptors in aged rats. Conclusion: GINST may be a potential natural agent for the protection against or treatment of oxidative stress-induced male subfertility and aging-induced male subfertility.