• Proceedings of the PSK Conference
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• 2003.10b
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• pp.95.1-95.1
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• 2003

Sopungsungi-won has been used as a traditional medicine for diabetes and it has been proved evidently as a potential remedy for type 2 diabetes mellitus. Both in vivo and in vitro experiments with water extract of Sopungsungi-won have been reported to exhibit anti-diabetic effects in our previous studies. In the present study, we have chosen Rheum undulatum (RU), which is the main component of Sopungsungi-won, to examine its anti-apoptotic effect on pancreatic b-cells, HIT-T15, against oxidative stress induced by hydrogen peroxide (H$_2$O$_2$). (omitted)

• Journal of Acupuncture Research
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• v.31 no.2
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• pp.75-85
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• 2014

Objectives : We investigated whether bee venom(BV) inhibit cell growth through enhancement of death receptor expressions in the human cervix cancer C33A cells. Methods : BV($1{\sim}5{\mu}g/ml$) inhibited the growth of cervix cancer C33A cells by the induction of apoptotic cell death in a dose dependent manner. Results : Consistent with apoptotic cell death, expression of Fas, death receptor(DR) 3, 4, 5 and 6 was increased concentration dependently in the cells. Moreover, Fas, DR3 and DR6 revealed more sensitivity to BV. Thus, We reconfirmed whether they actually play a critical role in anti-proliferation of cervix cancer C33A cells. Consecutively, expression of DR downstream pro-apoptotic proteins including caspase-8, -3, -9 was upregulated and Bax was concomitantly overwhelmed the expression of Bcl-2. NF-${\kappa}B$ were also inhibited by treatment with BV in C33A cells. Conclusions : These results suggest that BV could exert anti-tumor effect through induction of apoptotic cell death in human cervix cancer C33A cells via enhancement of death receptor expression, and that BV could be a promising agent for preventing and treating cervix cancer.

• Biomolecules & Therapeutics
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• v.19 no.4
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• pp.445-450
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• 2011

Preciously, we demonstrated that a novel NHE-1 inhibitor, KR-33028 attenuated cortical neuronal apoptosis induced by glutamate. In the present study, we investigated the signaling mechanism of neuroprotective effect of KR-33028 against glutamate-induced neuronal apoptosis, especially focusing on mitochondrial death pathway. Our data showed that glutamate induces a biphasic rise in mitochondrial $Ca^{2+}$ and that KR-33028 significantly prevents the second phase increase, but not the first phase increase in mitochondrial $Ca^{2+}$. Furthermore, KR-33028 restored the ${\Delta}{\Psi}_m$ dissipation and cytochrome c release into cytoplasm induced by glutamate in a concentration-dependent manner. The inhibition of mitochondrial $Ca^{2+}$ overload by ruthenium red also inhibited glutamate-induced apoptotic cell death, mitochondrial membrane potential, ${\Delta}{\Psi}_m$ dissipation and cytochrome c release. These data suggest that inhibition of mitochondrial $Ca^{2+}$ overload is likely to be attributable to anti-apoptotic effect of KR-33028. Taken together, our results suggest that anti-apoptotic effects of NHE-1 inhibitor, KR-33028 may be mediated through maintenance of mitochondrial function.

• Journal of Nutrition and Health
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• v.48 no.5
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• pp.451-456
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• 2015

Purpose: Neuronal apoptotic events induced by aging and hypoxic/ischemic conditions is an important risk factor in neurodegenerative diseases such as ischemia stroke and Alzheimer's disease. The peel of Citrus sunki Hort. ex Tanaka has long been used as a traditional medicine, based on multiple biological activities including anti-oxidant, anti-inflammation, and anti-obesity. In the current study, we examined the actions of fermented C. sunki peel extract against cobalt chloride ($CoCl_2$)-mediated hypoxic death in human neuroblastoma SH-SY5Y cells. Methods: Cell viability was measured by trypan blue exclusion. Expression of apoptosis related proteins and release of cytochrome c were detected by western blot. Production of intracellular reactive oxygen species (ROS) and apoptotic morphology were examined using 2',7'-dichlorofluorescin diacetate (DCF-DA) and 4',6-diamidino-2-phenylindole (DAPI) staining. Results: Exposure to $CoCl_2$, a well-known mimetic agent of hypoxic/ischemic condition, resulted in neuronal cell death via caspase-3 dependent pathway. Extract of fermented C. sunki peel significantly rescued the $CoCl_2$-induced neuronal toxicity with the cell viability and appearance of apoptotic morphology. Cytoprotection with fermented C. sunki peel extract was associated with a decrease in activities of caspase-3 and cleavage of poly (ADP ribose) polymerase (PARP). In addition, increase in the intracellular ROS and release of cytochrome c from mitochondria to the cytosol were inhibited by treatment with extract of fermented C. sunki peel. Conclusion: Based on these data, fermented C. sunki peel extract might have a protective effect against $CoCl_2$-induced neuronal injury partly through generation of ROS and effectors involved in mitochondrial mediated apoptosis.

• Journal of Acupuncture Research
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• v.24 no.2
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• pp.125-140
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• 2007

Objectives: This study was performed to investigate the effects of acupuncture therapy(AT, AT-9), electro-acupuncture therapy(EAT) and low level laser acupuncture therapy(LAT) at LRJ on the focal ischemia-induced by intraluminal filament insertion in rats. Methods : In the present syudy, the focal ischemia was induced by Intraluminal filament insertion into left middle cerebral artery. The subjects were divided into five groups after focal brain ischemia. (n=15, in each group) : Control with no treatment, AT with acupuncture at $LR_3$, AT-9 with acupuncture at $LR_3$ and rotating 9 times in a clockwise direction, EAT with electro-acupuncture at $LR_3$ and LAT with invasive laser acupuncture at $LR_3$. Anti-apoptotic and neuroprotective effects of acupuncture were observed by mGluR5 mRNA, Bax mRNA, Bcl-2 mRNA, Cytochrome C protein, Cresyl violet-stain and Choline acetyltransferase (ChAT)-stain in the hippocampus. Results: 1. In LAT, mGluR5, Cresyl violet-stain and ChAT-stain were increased. 2. In LAT, Cytochrome C protein was decreased. 3. In AT-9, Bax, Cytochrome C protein and the Bax/Bcl-2 ratio were decreased. 4. In AT-9, Bcl-2, Cresyl violet-stain and ChAT-stain were increased. 5. In EAT, Bcl-2 and Cresyl violet-stain were increased. Conclusions: These results suggests that LAT and AT-9 show anti-apoptotic and neuro-protective effects and that LAT and AT-9 may be useful for managing stroke by focal brain ischemia.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.105-115
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• 2006

Fucoidan has been shown to exhibit a host of biological activities, including anti-coagulant, anti-thrombotic, anti-tumourigenic, anti-inflammatory, anti-viral, anti-complementary and neuroprotective effects. In the present study, we attempted to determine the effects of Fucoidan on both apoptosis and cell proliferation in the hippocampal CA1 region and the dentate gyrus of gerbils after the induction of transient global ischemia. This experiment involved the use of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay as well as immunohistochemisty for caspase-3 and 5-bromo-2'-deoxyuridine (BrdU). The monosaccharide composition of the purified Fucoidan which had been extracted from Laminaria religiosa was utilized in this study. The present study clearly induces that apoptotic cell death and cell proliferation in the gerbil's hippocampal regions increased significantly following the induction of transient global ischemia and the results of this study also indicate that Fucoidan exerted a suppressive effect on this observed ischemia-induced increase in apoptosis within the CA1 and dentate gyrus, and also suppressed cell proliferation in the dentate gyrus.

• The Journal of Internal Korean Medicine
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• v.35 no.2
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• pp.184-194
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• 2014

Objectives : This study was designed to investigate the effect on lipoapoptosis of Alisma orientale extract against free fatty acid-induced cellular injury. Methods : HepG2 cells were used in an vitro model. HepG2 cells were treated with free fatty acids to generate a cellular model of nonalcoholic fatty liver disease (NAFLD). Using this cellular model, the anti-apoptotic effect and reducing steatosis of Alisma orientale extract against free fatty acid-induced cellular injury was evaluated by measuring steatosis and apoptosis. Results : Alisma orientale extract significantly attenuated free fatty acid-induced intracellular steatosis. Alisma orientale extract inhibited free fatty acid-mediated activation of pJNK, PUMA, BAX, caspase-3, and -9, and apoptotic kinases that are correlated with NAFLD. Alisma orientale extract also promoted Bcl-2, a anti-apoptotic protein. Conclusions : From the above, the Alisma orientale extract decreased the hepatocyte steatosis and showed the hepatocelluar protective effect by the regulation of apoptosis-related protein. It proposes the possibility of Alisma orientale extract to the treatment of nonalcoholic fatty liver disease in clinics.

• Journal of Embryo Transfer
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• v.30 no.1
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• pp.23-31
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• 2015

Catalpol, an iridoid glucoside, isolated from the root of Rehmannia glutinosa Libosch. It possesses a broad range of biological and pharmacological activity including anti-tumor, anti-inflammation and anti-oxidant by acting as a free radical scavenger. Therefore, in this study, the effects of catalpol on blastocyst development, expression levels of reactive oxygen species (ROS) and apoptotic index were investigated in porcine embryos. After in vitro maturation and fertilization, porcine embryos were cultured for 6 days in porcine zygote medium 3 (PZM-3) supplemented with catalpol (0, 100, 200 and $400{\mu}M$, respectively). Blastocyst development not significantly improved in the catalpol treated group when compared with control group. Otherwise, the intracelluar levels of ROS were decreased and the numbers of apoptotic nuclei were reduced in the catalpol ($100{\mu}M$) treated porcine blastocysts (P<0.05). On the other hand, blastocyst development was significantly improved in the catalpol ($100{\mu}M$) treated group when compared with the untreated catalpol group under $H_2O_2$ ($200{\mu}M$) induced oxidative stress (P<0.05). Otherwise, the intracellular levels of ROS in catalpol ($100{\mu}M$) treated group were significantly decreased in the untreated catalpol group under $H_2O_2$ ($200{\mu}M$) induced oxidative stress (P<0.05). Furthermore, the total cell numbers of blastocysts were significantly increased (P<0.05) in the catalpol ($100{\mu}M$) treated group under $H_2O_2$ ($200{\mu}M$) induced oxidative stress, whereas numbers of apoptoic nuclei were significantly reduced (P<0.05). In conclusion, our results indicate that treatment of catalpol may have important implications for improving developmental competence and preimplantation quality of porcine embryos through its anti-oxidant and anti-apoptotic effect.

• BMB Reports
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• v.35 no.3
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• pp.267-272
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• 2002

TNF-$\alpha$ elicits various responses including apoptosis, proliferation, and differentiation according to cell type. In neuronal PC12 cells, TNF-$\alpha$ induces moderate apoptosis while lipopolysarccaharide or trophic factor deprivation can potentiate apoptosis that is induced by TNF-$\alpha$. TNF-$\alpha$ initiates various signal transduction pathways leading to the activation of the caspase family, NF-${\kappa}B$, Jun N-terminal kinase, and p38 MAPK via the death domain that contains the TNF-$\alpha$ receptor. Inhibition of translation using cycloheximide greatly enhanced the apoptotic effect of TNF-$\alpha$. This implies that the induction of anti-apoptotic genes for survival by TNF-$\alpha$ may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic genes for survival by TNF-$\alpha$ may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic Bcl-2 family member, was highly expressed in response to TNF-$\alpha$. In this study, we examined the anti-apoptotic role of p38 MAPK that is activated by TNF-$\alpha$ in neuronal PC12 cells. The phosphorylation of p38 MAPK in response to TNF-$\alpha$ slowly increased and lasted several hours in the PC12 cell and DRG neuron. This specific inhibitor of p38 MAPK, SB202190, significantly enhanced the apoptosis that was induced by TNF-$\alpha$ in PC12 cells. This indicates that the activation of p38 MAPK could protect PC12 cells from apoptosis since there is no known role of p38 MAPK in resoonse to TNF-$\alpha$ in neuron. This discovery could be evidence for the neuroprotective role of the p38 MAPK.

• Journal of Life Science
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• v.26 no.10
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• pp.1130-1136
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• 2016

The purpose of this study was to investigate the anti-proliferative and apoptotic effects of acid extract of Gracilaria verrucosa (AEG) on RC-58T/h/SA#4 primary human prostate cancer cells. AEG significantly decreased the cell viability of prostate cancer cells in a dose-dependent manner. AEG also showed relatively low cytotoxicity on normal cell (RWPE-1). The morphology of prostate cancer cells treated with AEG was distorted to shrunken cell masses. In addition, it was revealed that AEG induced cell death as evidenced by increased formation of apoptotic body and nuclear condensation. Furthermore, AEG clearly modulated the down regulation of Bcl-2 (anti-apoptotic)/Bax (pro-apoptotic) family and activated caspase-3 as an effector caspase in a dose-dependent manner. AEG inhibited cell proliferation induced by environmental hormones as a bisphenol A in a dose-dependent manner. These results indicate that AEG act as anti-proliferative effects as a potential therapeutic agent on primary human prostate cancer cells.