• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1584-1592
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• 2006

Houttuynia cordata Thunb, well known as 'E-Sung-Cho' in Korea, is traditional medicinal plant generally used in Oriental medicine therapy. We previously reported that the water extract of H. cordata inhibited cell proliferation and induced apoptosis in human breast carcinoma cells. In the present study, we investigated the biochemical mechanisms of anti-proliferative effects by the methanol extract of H. cordata (MEHC) in human lung carcinoma A549 cells. It was found that MEHC could inhibit the cell growth in a dose-dependent manner, which was associated with morphological change and apoptotic cell death as determined by formation of apoptotic bodies, DNA fragmentation and increased populations of apoptotic-sub G1 phase cells. Apoptosis of A549 cells by MEHC was also connected with a down-regulation of anti-apoptotic Bcl-2 and inhibitor of apoptosis proteins (IAPs) expression. MEHC treatment induced the proteolytic activation of caspase-3, caspase-8 and caspase-9, and a concomitant inhibition of poly(ADP-ribose) polymerase (PARP), ${\beta}$-catenin and phospholipase (PLC)-${\gamma}$1 protein expression. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of H. cordata.

• Parasites, Hosts and Diseases
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• v.50 no.1
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• pp.1-6
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• 2012

$Toxoplasma$ $gondii$ penetrates all kinds of nucleated eukaryotic cells but modulates host cells differently for its intracellular survival. In a previous study, we found out that serine protease inhibitors B3 and B4 (SERPIN B3/B4 because of their very high homology) were significantly induced in THP-1-derived macrophages infected with $T.$ $gondii$ through activation of STAT6. In this study, to evaluate the effects of the induced SERPIN B3/B4 on the apoptosis of $T.$ $gondii$-infected THP-1 cells, we designed and tested various small interfering (si-) RNAs of SERPIN B3 or B4 in staurosporine-induced apoptosis of THP-1 cells. Anti-apoptotic characteristics of THP-1 cells after infection with $T.$ $gondii$ disappeared when SERPIN B3/B4 were knock-downed with gene specific si-RNAs transfected into THP-1 cells as detected by the cleaved caspase 3, poly-ADP ribose polymerase and DNA fragmentation. This anti-apoptotic effect was confirmed in SERPIN B3/B4 overexpressed HeLa cells. We also investigated whether inhibition of STAT6 affects the function of SERPIN B3/B4, and vice versa. Inhibition of SERPIN B3/B4 did not influence STAT6 expression but SERPIN B3/B4 expression was inhibited by STAT6 si-RNA transfection, which confirmed that SERPIN B3/B4 was induced under the control of STAT6 activation. These results suggest that $T.$ $gondii$ induces SERPIN B3/B4 expression via STAT6 activation to inhibit the apoptosis of infected THP-1 cells for longer survival of the intracellular parasites themselves.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.942-949
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• 2010

Morus alba L., a kind of Oriental medicinal herbs, has been traditionally used to treat pulmonary asthma and congestion. According to recent studies, extracts of M. alba L. have showed anti-inflammatory, anti-oxidant, anti-tumor and hypoglycemic effects. However, the molecular mechanisms on how it acts as a death-inducer in cancer cells have not been fully understood. In this study, we investigated the cell death effects of methylene chloride extracts of M. alba L. (MEMA) in A549 human lung carcinoma cells. It was shown that MEMA induced the apoptotic cell death proved by increased sub-G1 phase cell population, apoptotic body formation and chromatin condensation. MEMA treatment induced the expression of death receptor-related proteins such as death receptor (DR) 4, DR5, Fas and FasL, which further triggered the activation of caspase-8 and the cleavage of Bid in a concentration-dependent manner. However, MEMA reduced anti-apoptotic Bcl-2 and Bcl-xL expression which contributed to the loss of mitochondrial membrane potential (MMP), and the activations of caspase-9 and caspase-3. Meanwhile, the morphological study indicated a characteristic finding of autophagy, such as the formation of autophagosomes in MEMA-treated cells. Furthermore, markers of autophagy, namely, the increased MDC-positive cells, conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II and increased beclin-1 accumulation, were observed. Taken together, these findings demonstrated that MEMA triggered both autophagy and apoptosis in A549 cancer cells. They might suggest that M. alba L. could be a prospective clinical application to treat human lung cancers.

• Bulletin of the Korean Chemical Society
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• v.30 no.4
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• pp.897-901
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• 2009

Heme oxygenase-1 (HO-1) is an anti-inflammatory and anti-apoptotic protein and has been applied to various gene therapy researches. However, constitutive expression of HO-1 may induce deleterious side effects. In this research, hypoxia inducible HO-1 expression plasmid, pEpo-SV-HO-1, was constructed with the erythropoietin (epo) enhancer and simian virus 40 (SV40) promoter to avoid these unwanted side effects. Dexamethasone conjugated polyethylenimine (PEI-Dexa) was used as a gene carrier. It was previously reported that dexamethasone protected cardiomyocytes from apoptosis under hypoxia. In this research, PEI-Dexa reduced the caspase-3 level in hypoxic H9C2 cardiomyocytes as a derivative of dexamethasone, suggesting that PEI-Dexa is an anti-apoptotic reagent as well as a gene carrier. pEpo-SV-HO-1 was transfected to H9C2 cardiomyocytes using PEI-Dexa and the cells were incubated under normoxia or hypoxia. HO-1 expression was induced in the pEpo-SV-HO-1 transfected cells under hypoxia. In addition, cell viability under hypoxia was higher in the pEpo-SV-HO-1 transfected cells than the pEpo-SV-Luc transfected cells. Also, caspase-3 level was reduced in the pEpo-SV-HO-1 transfected cells under hypoxia. In addition to the anti-apoptotic effect of PEI-Dexa, hypoxia inducible HO-1 expression by pEpo-SVHO- 1 may be helpful to protect cardiomyocytes under hypoxia. Therefore, pEpo-SV-HO-1/PEI-Dexa complex may be useful for ischemic heart disease gene therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.1
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• pp.51-55
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• 2004

Sopungsungi-won has been used as a traditional medicine for diabetes and it has been proved to be a potential remedy for type 2 diabetes mellitus. We previously reported that water extract of Sopungsungi-won exhibits anti-diabetic effects both in vivo and in vitro experiments. In the present study, we have chosen to examined anti-apoptotic effect of Rheum undulatum, which is the main component of Sopungsungi-won, on pancreatic ${\beta}-cells$, HIT-T15, against hydrogen peroxide $(H_2O_2)$. oxidative stress. To investigate the anti-apoptotic effect of Rheum undulatum water extract (RUWE) against $H_2O_2-induced$ apoptosis in pancreatic ${\beta}-cell$ line of hamster, HIT-T15, MTT assay, DAPI staining, TUNEL assay, RT-PCR and caspase-3 enzyme assay were performed. The morphological analysis demonstrated that cells treated with $H_2O_2$ exhibited classical apoptotic features, while such changes was reduced in cells pre-treated with RUWE. In addition, RUWE pre-treated cells prior to $H_2O_2$ treatment induced increase of levels of bcl-2 expression and decrease of caspase-3 enzyme activity compared to cells treated with $H_2O_2$ only. These results provide the possibility of usage of RU in patients with progressively deteriorated diabetes.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.183-187
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• 2016

Rhizomes of Boesenbergia pandurata (Roxb.) Schlecht have been reported to contain active compounds with anticancer properties. This research was carried out to examine anti-proliferative and apoptotic induction against HeLa and Vero cells-line. Dried powder of B. pandurata rhizomes was extracted by a maceration method using 90% ethanol. Cytotoxic assays to determine $IC_{50}$ and anti-proliferative effects were carried out by MTT methods. Observation of apoptosis was achieved with double staining using acridine orange and ethidium bromide. The results showed that ethanolic extract of B. pandurata was more cytotoxic against HeLa cells ($IC_{50}$ of $60{\mu}g/mL$) than Vero cells ($IC_{50}$ of $125{\mu}g/mL$). The extract had higher anti-proliferative activity as well as apoptotic induction in HeLa than Vero cells. Therefore, it was concluded that the ethanolic extract of B. pandurata had anti-proliferative as well as apoptosis induction activity dependent on the cell type.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.235-248
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• 2018

Ursolic acid (UA) is a natural triterpene compound found in various fruits and vegetables. There is a growing interest in UA because of its beneficial effects, which include anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-carcinogenic effects. It exerts these effects in various tissues and organs: by suppressing nuclear factor-kappa B signaling in cancer cells, improving insulin signaling in adipose tissues, reducing the expression of markers of cardiac damage in the heart, decreasing inflammation and increasing the level of anti-oxidants in the brain, reducing apoptotic signaling and the level of oxidants in the liver, and reducing atrophy and increasing the expression levels of adenosine monophosphate-activated protein kinase and irisin in skeletal muscles. Moreover, UA can be used as an alternative medicine for the treatment and prevention of cancer, obesity/diabetes, cardiovascular disease, brain disease, liver disease, and muscle wasting (sarcopenia). In this review, we have summarized recent data on the beneficial effects and possible uses of UA in health and disease managements.

• International Journal of Oral Biology
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• v.43 no.2
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• pp.61-68
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• 2018

Codium fragile (Suringar) Hariot is an edible green seaweed that belong to the Codiaceae family and has been used in Oriental medicine for the treatment of enterobiasis, dropsy, and dysuria. Methanol extract of codium fragile has anti-oxidant, anti-inflammatory and anti-cancer properties, although the anti-cancer effect on oral cancer has not yet been reported. In this study, we investigated the anti-cancer activity and the mechanism of cell death by methanol extracts of Codium fragile (MeCF) on human FaDu hypopharyngeal squamous carcinoma cells. Our data showed that MeCF inhibits cell viability in a dose-dependent manner, and markedly induced apoptosis, as determined by the MTT assay, Live/Dead assay, and DAPI stain. In addition, MeCF induced the proteolytic cleavage of procaspase -3, -7, -9 and poly(ADP-ribose) polymerase(PARP), and upregulated or downregulated the expression of mitochondrial-apoptosis factor, Bax(pro-apoptotic factor), and Bcl-2(anti-apoptotic factor). Futhermore, MeCF induced a cell cycle arrest at the G1/S phase through suppressing the expression of the cell cycle cascade proteins, p21, CDK4, CyclinD1, and phospho-Rb. Taken together, these results indicated that MeCF inhibits cell growth, and this inhibition is mediated by caspase- and mitochondrial-dependent apoptotic pathways through cell cycle arrest at the G1/S phase in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, methanol extracts of Codium fragile can be provided as a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

• Korean Journal of Acupuncture
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• v.25 no.1
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• pp.229-246
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• 2008

Objectives : Acupoints of LR1(Dadun)${\cdot}$HT9(Shaochong), KI10(Yingu)${\cdot}$HT3(Shaohai) are used as controlling the diseases from heart problems. Especially, when they are used, tonification or sedation techniques method is taken as a controlling the medication for an early stroke in the Korean medicine. So the aim of this study is to investigate the anti-apoptotic and neuroprotective effects of Acupuncture techniques of tonification or sedation at LR1${\cdot}$HT9, KI10${\cdot}$HT3 on the focal ischemia induced by intraluminal filament insertion in rats. Materials and Methods : The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The animals were divided into five groups (n=7 in each group) : Control group, no therapy group after ischemia induced; AT-1; acupuncture therapy group at LR1${\cdot}$HT9, KI10${\cdot}$HT3 after ischemia-induced. AT-2; acupuncture therapy at right LR1, HT9(forward direction), KI10${\cdot}$HT3(opposite direction) inserting to the direction of route of the each meridian. AT3; acupuncture therapy at right LR1, HT9(twirling forward with the thumb of right hand 9 times), KI10${\cdot}$HT3(twirling forward with the forefinger of right hand 6 times) AT-4; acupuncture therapy at right LR1, HT9(forward direction, twirling forward with the thumb of right hand 9 times), KI10${\cdot}$HT3(opposite direction, twirling forward with the forefinger of right hand 6 times) inserting to the direction of route of the each meridian. The anti-apoptotic and neuroprotective effects of Acupuncture techniques of tonification or sedation at LR1, HT9, KI10${\cdot}$HT3 were observed by Bax, Bcl-2, mGluR5, Cytochrome c, Cresyl violet and ChAT-stain. Results : The intensity of Bax and Bax/Bcl-2 ratio were increased in ACU-2 and ACU-4 group but decreased in ACU-3 group. The intensity of mGluR5 was increased in ACU-1, ACU-2, ACU-3 and ACU-4 group. The intensity of cytochrome c was decreased in ACU-3 and ACU-4 group. The density of neurons stained by Cresyl violet and ChAT were increased in ACU-1, ACU-3 and ACU-4 group. Conclusions : Our study suggests that acupuncture therapy of tonification at LR1, HT9 by twirling forward with the thumb of right hand 9times, sedation at KI10${\cdot}$HT3 by twirling forward with the forefinger of right hand 6 times after perpendicularly inserting needle shows anti-apoptotic and neuroprotective effects on cholinergic neuron in focal cerebral ischemia of the stroke in rats.

• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.81-98
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• 2006

Objectives : Acupuncture using a tonification or sedation techniques method is used as a controlling the medication for an early stroke in the Korean medicine. LR3 has indicatons of headache, vertigo, facial paralysis, apoplexy, epiepsy as the source acupoint of a liver meridian. So this study is aims to investigate the anti-apoptotic and neuroprotective effects of acupuncture on the focal ischemia induced by intraluminal filament insertion in rats. Methods : The focal ischemia was induced by intraluminal filament insertion into middle cerebral artery. The animals were divided into seven groups (n=8 in each group) : Normal, intactness group; Conrol group, no therapy group after being ischemia induced; MA-l, acupuncture perpendicularly without Tonification or Sedation techniques at LR3 after being ischemia induced; MA-2, acupuncture obliquely towards the knee at LR3 after being ischemia induced; MA-3, acupuncture obliquely towards the toe at LR3 after being ischemia induced; MA-4, acupuncture obliquely towards the knee and rotate 9 times in a clockwise direction at LR3 after being ischemia induced; MA-5, acupuncture obliquely towards the toe and rotate 6 times in a counterclockwise direction at LR3 after being ischemia induced. The anti-apoptotic and neuroprotective effects of Acupuncture techniques of tonification or sedation at LR3 are observed by mGluR5, Bax, Cresyl violet, ChAT-stain and NGF. Results : The intensity of mGluR5 and the density of ChAT was increased in MA-1 group. The intensity of Bax was decreased in MA-3, MA-4 group. The density of neurons stained by Cresyl violet and ChAT was increased in MA-2, MA-3, MA-4, MA-5 group. The density of neurons stained by NGF was only increased in MA-4 group. Conclusions : Our study suggests that acupuncture perpendicularly without Tonification or Sedation techniques and obliquely towards the knee and rotate 9 times in a clockwise direction(Tonifying technique) at LR3 after being ischemia induced at LR3 shows anti-apoptotic and neuroprotective effects on cholinergic neuron in focal cerebral ischemia of the stroke in rats.