• Journal of Sasang Constitutional Medicine
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• v.12 no.2
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• pp.162-170
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• 2000

Purpose : Studies on the Regulatory Effect of Cytokine Production in Taumin Patients with Cerebral Infarction by Cheongsimyeonjatang Method : ELISA(enzyme-linked immuno-sorbent assay) Result : Chungsimyeunjatang(CYT) is a prescription for the cerebral infarction (CI) patients of Taeumin according to Sasang constitution philosophy. Taeumin patients with CI were treated with CYT during the acute stage. Clinical signs of CI disappeared markedly in about two to four weeks after oral administration of CYT in all patients. The mean interleukin (IL)-2 plasma levels were slightly lower in the patients with CI than in the normal groups, whereas the mean IL-4, IL-6 and IgE levels were significantly higher in the patients. There were no significant differences in $interferon-{\gamma}$ $(IFN-{\gamma})$ levels between the groups. Serum $IFN-{\gamma}$ and IL-2 levels derived from T helper (Th)1 cells were elevated significantly in the patients with CI by CYT administration. Significant reduced plasma levels of IL-4 and IL-6 derived from Th2 cells and IgE were observed in the patients treated with CYT. During the period of CYT administration, there were no other adverse effects. The data indicate that CYT has a good CI treatment effect, and that its action may be due to regulation of cytokine Production.

• Journal of Sasang Constitutional Medicine
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• v.12 no.2
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• pp.153-161
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• 2000

1. Purpose This studies the regulatory effect of cytokine production in Soyangin patients with cerebral infarction by Yangkyuksanhwatang. 2 Method ELISA 3. Result & Conclusion Yangkyuksanhwatang(YST) is a prescription for the cerebral infarction (CI) patients of Soyangin according to Sasang constitution philosophy. Soyangin patients with CI were treated with YST during the acute stage. Clinical signs of CI disappeared markedly in about 2 to 4 weeks after oral administration of YST in all patients. The mean interleukin (IL)-2 plasma levels were slightly lower in the patients with CI than in the normal groups, whereas the mean IL-4, IL-6 and IgE levels were significantly higher in the patients. There were no significant differences in interferon- ${\gamma}$ (IFN- ${\gamma}$ ) levels between the groups. Serum IFN- ${\gamma}$ and IL-2 levels derived from T helper (Th)1 cells were elevated significantly in the patients with CI by YST administration. Significant reduced plasma levels of IL-4 and IL-6 derived from Th2 cells and IgE were observed in the patients treated with YST. During the period of YST administration, there were no other adverse effects. The data indicate that YST has a good CI treatment effect, and that its action may be due to regulation of cytokine production.

• The Journal of Internal Korean Medicine
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• v.22 no.2
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• pp.127-134
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• 2001

The purpose of this investigation is to evaluate the effects of Samwha-tang(三化湯) Extracts on reversible forebrain ischemia experimentally induced from the occlusion of middle cerebral artery. The volume of cerebral ischemia, the volume of cerebral edema, and the change of pyramidal neuron of the CA1 area in hippocampus through light microscopy were investigated. we obtained the following results. The volume of the control group, which had ischemic damage was 21%, and the volume of the sample group, which had ischemic damage, was 16%. The ratio of the volume of the right/left hemisphere was 117.2 in the control group, and 108.8 in the sample group. Also, the light microscopy revealed that the pyramidal cells of CA1 area in hippocampus had many damages like changes into discontinuous and unsystematic forms. But, in the sample group, the cells were less damaged compared with the control group.

• Journal of Korean Neurosurgical Society
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• v.37 no.1
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• pp.54-58
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• 2005

Objective: The purpose of this study is to determine the time evolution and distribution of cerebral apoptosis using the middle cerebral artery occlusion model in rats. Methods: A total of twenty four male rats - with 2, 3, 4, 6, 8, 12, 24 and 48 hours of middle cerebral artery occlusion respectively - were studied. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling(TUNEL) method was used for the observation of the apoptotic cells. The apoptotic ratio was calculated and the distribution of apoptosis was inspected in the pyriform cortex, basal ganglia and middle cerebral artery territory cortex. The rats were divided into three groups(Group I : $2{\sim}4$ hours of occlusion, Group II : $6{\sim}$12 hours of occlusion, Group III : $24{\sim}48$ hours of occlusion). Results: In this study, the proportion of apoptosis increased with the duration of middle cerebral artery occlusion and reached a maximum after about 12 hours of middle cerebral artery occlusion. The mean values of the apoptotic ratio were $30.7{\pm}11.3%$ in group I, $60.8{\pm}2.6%$ in group II and $48.7{\pm}0.7%$ in group III. The distribution of apoptosis differed in the pyriform cortex, basal ganglia and middle cerebral artery territory cortex according to the duration of time of the middle cerebral artery occlusion. Conclusion: In the middle cerebral artery occlusion model of the rats, apoptosis is found to increase according to the occlusion time, reaching a peak after 6 hours, and the distribution of apoptosis changed from the pyriform cortex to the basal ganglia and middle cerebral artery territory cortex.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.1
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• pp.192-198
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• 2009

Banhabaikchulcheunma-tang (BBCT), a prescription composed of thirteen herbal mixtures, has been widely used in the treatment of brain disorders in Oriental Medicine. However, the mechanisms by which the formula affects on the production of pro-inflammatory cytokines in cerebral infarction (CI) patients remain unknown yet. The levels of secretory protein of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-a, interlukin (IL)-1b, and IL-6, were significantly increased in lipopolysaccharide (LPS)-stimulated THP-1 differentiated macrophage-like (THP-1/M) cells and Peripheral blood mononuclear cells (PBMCs) from CI patients. However, pretreatment with BBCT significantly inhibited the secretion of pro-inflammatory cytokines, including TNF-a, IL-1b, and IL-6, in THP-1/M cells and PBMCs from CI patients with stimulus. Thus, these data indicate that BBCT may be beneficial in the cessation of inflammatory processes of cerebral infarction through suppression on the production of pro-inflammatory cytokines.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3219-3226
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• 2014

Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2. ${\beta}$-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.2
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• pp.145-153
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• 2018

The subgranular zone (SGZ) of hippocampal dentate gyrus (HDG) is a primary site of adult neurogenesis. Toll-like receptors (TLRs), are involved in neural system development of Drosophila and innate immune response of mammals. TLR2 is expressed abundantly in neurogenic niches such as adult mammalian hippocampus. It regulates adult hippocampal neurogenesis. However, the role of TLR2 in adult neurogenesis is not well studied in global or focal cerebral ischemia. Therefore, this study aimed to investigate the role of TLR2 in adult neurogenesis after photochemically induced cerebral ischemia. At 7 days after photothrombotic ischemic injury, the number of bromodeoxyuridine (BrdU)-positive cells was increased in both TLR2 knock-out (KO) mice and wild-type (WT) mice. However, the increment rate of BrdU-positive cells was lower in TLR2 KO mice compared to that in WT mice. The number of doublecortin (DCX) and neuronal nuclei (NeuN)-positive cells in HDG was decreased after photothrombotic ischemia in TLR2 KO mice compared to that in WT mice. The survival rate of cells in HDG was decreased in TLR2 KO mice compared to that in WT mice. In contrast, the number of cleaved-caspase 3 (apoptotic marker) and the number of GFAP (glia marker)/BrdU double-positive cells in TLR2 KO mice were higher than that in WT mice. These results suggest that TLR2 can promote adult neurogenesis from neural stem cell of hippocampal dentate gyrus through increasing proliferation, differentiation, and survival from neural stem cells after ischemic injury of the brain.

• The Korea Journal of Herbology
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• v.27 no.2
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• pp.77-83
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• 2012

Objectives : This work was designed to investigate the effect of The root of Achyranthes japonica Nakai (AJN) water extract on serum deprivation reperfusion-induced apoptosis in PC-12 cells and transient middle cerebral artery occlusion (tMCAO)-induced ischemic brains of rats. Methods : Apoptosis in PC12 cells was induced by serum deprivation and reperfusion. The cells were treated with AJN water extract at doses of 0.5 and 1.0 mg/ml for 24 hr after inducing the apoptosis. Cell viability was determined by WST-1 assay. The expression of caspase-3 protein was determined by Western blot. Ischemic brains were prepared from tMCAO-induced ischemic rats after oral administration with AJN at dose of 50 and 100 mg/kg, and then brain infarction was measured by TTC staining. Results : AJN significantly increased the cell viability in apoptocic-induced PC-12 cells, and also decreased the expression of caspase-3 protein. Furthermore, the administration of AJN significantly inhibited tMCAO-induced brain infarction in rats. Conclusions : Our results suggest that AJN extract has a neuroprotective property via suppressing the apoptosis in PC12 cells and the infarction of ischemic brains.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.829-836
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• 2003

Seogakjihwang-tang (SJT) was widely used to treat patients suffering from cerebral infarction. But scientific investigation has been carried out very little. The aim of the present study is to investigate the effect of SJT on the production of various cytokines in the patients with cerebral infarction (CI). We investigated interleukin (IL)-4, IL-10 and transforming growth factor (TGF)-1 in the sera of 27 patients with cerebral infarction under consciousness disorders and 10 normal controls using an originally devised sensitive sandwich enzyme-linked immunosorbent assay (ELISA). We found that plasma levels of IL-4 were slightly elevated in patients with cerebral infarction, whereas plasma levels of IL-10 (P<0.001) and TGF-1 were reduced. Peripheral blood mononuclear cells (PBMC) obtained from the patient with CI were cultured for 24 h in the presence or absence of lipopolysaccharide (LPS) or phytohaemagglutinin (PHA). The amount of IL-4, IL-10 and TGF-1, in culture supernatant, was significantly increased in the LPS or PHA treated cells compared to unstimulated cells (P<0.05), We also show that increased cytokines IL-4, and IL-10 level was significantly inhibited by SJT in a dose-dependent manner. Maximal inhibition rate of IL-4 and IL-10 production by SJT was 45.63.3% and 614.7% for LPS-stimulated cell and 27.31.2% and 83.62% for PHA-stimulated cells, respectively (P<0.05). On the other hand, SJT significantly increased the LPS or PHA-induced TGF-1 production (P<0.05). These data suggest that SJT has a regulatory effect on the cytokines production, which might explain its beneficial effect in the treatment of CI.

• The Korean Journal of Pain
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• v.21 no.2
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• pp.119-125
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• 2008

Background: Cerebral blood vessels are innervated by sympathetic nerves from the superior cervical ganglia (SCG), and these nerves may influence the cerebral blood flow. The purpose of the present study was to evaluate the neuroprotective effect of superior cervical sympathetic ganglion block in rats that were subjected to focal cerebral ischemia/reperfusion injury. Methods: Eighty male Sprague-Dawley rats (270-320 g) were randomly assigned to one of two groups (the ropivacaine group and a control group). In all the animals, brain injury was induced by middle cerebral artery (MCA) reperfusion that followed MCA occlusion for 2 hours. The animals of the ropivacaine group received $30{\mu}l$ of 0.75% ropivacaine, and their SCG. Neurologic score was assessed at 1, 3, 7 and 14 days after brain injury. Brain tissue samples were then collected. The infarct ratio was measured by 2.3.5-triphenyltetrazolium chloride staining. The terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeled (TUNEL) reactive cells and the cells showing caspase-3 activity were counted as markers of apoptosis at the caudoputamen and frontoparietal cortex. Results: The death rate, the neurologic score and the infarction ratio were significantly less in the ropivacaine group 24 hr after ischemia/reperfusion injury. The number of TUNEL positive cells in the ropivacaine group was significantly lower than those values of the control group in the frontoparietal cortex at 3 days after injury, but the caspase-3 activity was higher in the ropivacaine group than that in the control group at 1 day after injury. Conclusions: The study data indicated that a superior cervical sympathetic ganglion block may reduce the neuronal injury caused by focal cerebral ischemia/reperfusion, but it may not prevent the delayed damage.