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Inhibitory Effects of Extracts from Traditional Herbal Drugs on 5-Hydroxytryptophan-Induced Diarrhea in Mice (생쥐에서 5-Hydroxytryptophan에 의한 설사에 대한 각종 전통 생약 추출물의 억제 효과)

  • Yoo, Jae-Sun;Jung, Jun-Sub;Lee, Tae-Hee;Son, Kun-Ho;Suh, Hong-Won;Song, Dong-Keun;Kim, Yung-Hi
    • Korean Journal of Pharmacognosy
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    • v.26 no.4
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    • pp.355-359
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    • 1995
  • To find serotonin(5-hydroxytryptamine, 5-HT)-antagonizing activities in traditional herbal drugs, crude extracts from 66 kinds of traditional herbal drugs were randomly screened for inhibitory effects on 5-hydroxytryptophan(HTP)-induced diarrhea in mice. Intraperitoneal injection of 5-HTP(2.5 mg/kg) induced diarrhea in 92% of mice, when observed from 10 to 15 min after injection. Crude extracts(2 g/kg) from 66 kinds of traditional herbal drugs were orally pretreated for 1 h before 5-HTP injection. Of the 66 herbal drugs screened, Ephedrae Herba(麻黃), Cimicifugae Rhizoma(升麻), Anisi stellati Fructus(八角茴香), Aurantii Fructus(枳實), Polygalae Radix(遠志) showed the most potent inhibiting activities against 5-HTP(2.5 mg/kg)-induced diarrhea in mice. There are at least 3 possible mechanisms that would be responsible for the inhibitory effect of crude extracts on 5-HTP-induced diarrhea; 1) crude extract-induced inhibition of the activity of aromatic aminoacid decarboxylase catalyzing the conversion of 5-HTP to 5-HT, 2) crude extract-induced blockade of 5-HT receptor(s) in the gastrointestinal tract responsible for 5-HTP-induced diarrhea, 3) crude extract-induced inhibition of gastrointestinal activity, irrespective of 5-HT system. The exact mechanisms and molecules, responsible for the inhibitory effect of crude extracts on 5-HTP-induced diarrhea remain to be clarified.

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Induction of Apoptosis in HT-29 Human Colorectal Cancer by Aloin (인간 대장암 세포 HT-29에서 Aloin에 의한 Apoptosis 유도)

  • Yoo, Eun-Seon;Woo, Joong-Seok;Kim, Sung-Hyun;Lee, Jae-Han;Han, So-Hee;Jung, Soo-Hyun;Park, Young-Seok;Kim, Byeong-Soo;Kim, Sang-Ki;Park, Byung-Kwon;Jung, Ji-Youn
    • Journal of Food Hygiene and Safety
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    • v.34 no.5
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    • pp.495-501
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    • 2019
  • Aloin [1,8-Dihydroxy-10-(${\beta}$-D-glucopyranosyl)-3-(hydroxymethyl)-9(10H)-anthracenone], is a natural anthraquinone from aloe. It has been shown to have antioxidant and anticancer effects in various types of human cancer cells, but the anticancer effects of aloin in human colorectal cancer cells HT-29 have not been elucidated. In this study, possible mechanisms by which aloin exerts its apoptotic action in cultured human colorectal cancer HT-29 cells were investigated. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows that treatment with aloin (0, 100, 200, 300 and $400{\mu}M$) reduced cell viability in a concentration-dependent manner in HT-29 and showed no effects on cell proliferation in A375SM and AGS cells. In addition, it was confirmed that apoptotic body was significantly increased as shown by 4',6-diamidino-2-phenylindole (DAPI) staining, and increased apoptosis rate by flow cytometry in HT-29 cells treated with aloin (0, 200 and $400{\mu}M$). We confirmed by western blotting that aloin activated Bax (pro-apoptotic), cleaved-poly (ADP-ribose) polymerase (PARP) and caspase-3, -8 and Bcl-2 (anti-apoptotic) were not changed compared with the control. Aloin induced up-regulation of phospho-p38 and down-regulation of phospho-extracellular signal-regulated kinase (ERK)1/2. Therefore, aloin suppressed the growth inhibitory effects by the induction of apoptosis in human colorectal cancer cells and has potential as a cancer preventive medicine.

Acupuncture Effects of Fatty Mice Induced by High Fat Diet (침 자극이 고지방식이로 유발된 비만 백서에 미치는 영향)

  • Woo, Chang-Hoon;Lee, Yong-Eun;Roh, Sung-Soo;Kim, Jae-Soo
    • Journal of Korean Medicine Rehabilitation
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    • v.24 no.3
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    • pp.1-9
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    • 2014
  • Objectives The aim of this study was to investigate the effects of acupuncture on weight loss, food intake, lipid metabolism, adipogenesis. Methods Four week-old C57BL/6J mice acclimatized to the laboratory environment for 1 week were allocated into four groups of 6~8 mice each: normal diet group, high fat diet group, high fat diet group and treated with acupuncture at HT7, high fat diet group and treated with acupuncture at ST36 for 90days. High fat diet group was used to control group. Results 1) Body weight, food intake of the ST36, HT7 groups decreased compared with those of control group. ST36 group was more effective with body weight decrease, and HT7 group was more effective with food intake decrease. 2) NEFA, TG, TC, ALT, AST of the ST36, HT7 groups decreased compared with those of control group. ST36 group was more effective. 3) The expression of SREP-1c, SREBP-2 of the ST36 group decreased compared with those of control group. These decreased rates were statistically significant. SREBP-2 of the HT7 group decreased significantly compared to the control group. 4) LXR, FAS, SCD of the ST36 group decreased significantly compared with control group. 5) p-ACC, HMGCR of the ST36 group decreased significantly compared with those of control group. HMGCR of the HT7 group decreased significantly compared with control group. Conclusions These results suggest that ST36, HT7 acupuncture may be used prevent or treat the obesity induced by high fat diet.

Postoperative Complications after Preoperative Chemoradiotherapy Combined with Hyperthermia in Locally Advanced Rectal Cancer (국소 진행성 직장암의 수술전 동시 화학방사선치료와 온열치료병합시 수술후 부작용)

  • Yea, Ji Woon
    • Progress in Medical Physics
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    • v.25 no.2
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    • pp.89-94
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    • 2014
  • We investigated whether regional hyperthermia (HT) increased post-surgical complications in patients with locally advanced rectal cancer treated with preoperative concurrent chemoradiotherapy (CCRT). Between 1996 and 2007, 205 patients treated with preoperative CCRT and curative surgery were evaluable for the analysis of acute and late toxicities. A total dose of 39.6 Gy or 45 Gy was delivered concurrently with one or two cycles of chemotherapy (5-fluorouracil, leucovorin). Eighty-eight patients received regional HT twice a week using an 8-MHz radiofrequency capacitive heating device. Surgery was performed 4~6 weeks after the completion of preoperative CCRT. The median age was 59 years (range, 18~83) and the median follow-up period was 61months (range, 2~191). The 5-year overall survival and complication-free survival rate of all patients was 77.4% and 73.7%, respectively. Early leakage, delayed leakage, anastomotic stricture, fistula, and small bowel obstruction occurred in 1.0%, 2.9%, 1.5%, 5.9%, and 17.1%, respectively. HT did not increase all kinds of complications. The 5-year complication-free survival rate was 71.8% in the non-HT group and 76.3% in the HT group (p=0.293). Regional HT did not increase postoperative complications in patients with locally advanced rectal cancer treated with preoperative CCRT followed by curative surgery.

Growth Acceleration and Acclimatization of In Vitro Plantlets derived from Apical Meristem of Sweet Potato (고구마의 경정조직 유래 기내 소식물체의 생장촉진과 순화)

  • ;;Shiro Higashi
    • Korean Journal of Plant Tissue Culture
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    • v.26 no.2
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    • pp.115-119
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    • 1999
  • The single node cuttings of sweet potato (cv. Mokpo #29) plantlets maintained in vitro were cultured with (MF+) or without membrane filter (MF-) under photomixotrophic (PM), hetrotrophic (HT) and autotrophic (AT) conditions. Shoot length was the greatest (11.9cm) in 3$0^{\circ}C$ (HT) treatment and it was the shortest (3.4 cm) in $25^{\circ}C$ (PM) treatment. Nodal explants cultured in 3$0^{\circ}C$ treatment looked more vigorous than those of $25^{\circ}C$ in appearance, and node number was the greatest (10.5 per plantlet) among the treatments. But plantlets grew in 3$0^{\circ}C$ (HT) treatment were observed all overgrown. The size in leaf area was about 2 times greater and shoot length was about 2 times shorter in PM than in HT condition. Percent dry matter of shoots was 5.9% (HT) and 7.4% (PM) in $25^{\circ}C$ treatment and 6.1% (HT) and 7.4% (PM) in 3$0^{\circ}C$ treatment. Plantlets cultured in the MF+ treatments were less succulent than those cultured in the MF- treatment. Vitrified plantlets were examinated 14.8% (both $25^{\circ}C$ and 3$0^{\circ}C$) in PM condition and 22.2% ($25^{\circ}C$) and 31.5% (3$0^{\circ}C$) in HT condition. Sucrose was necessary for the survival of in vitro plantlets. In the sucrose-free medium, explants cultured in the MF- had turned yellow and were dead after 30 days of culture. But explants cultured in the MF+ were alive and produced plantlets with shoot and root (AT). On the other hand, the survival of explants on the MS basal medium (sucrose-free and hormone-free) depended entirely upon the MF attachment.

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Effect of Snake Venom Toxin on Inhibition of Colorectal Cancer HT29 Cells Growth via Death Receptors Mediated Apoptosis

  • Shim, Yoon Seop;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.31 no.2
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    • pp.87-98
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    • 2014
  • Objectives : We investigated whether snake venom toxin(SVT) from Vipera lebetina turanica sensitizes HT29 human epithelial colorectal cancer cells to tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) induced apoptosis in cancer cells. Methods : Cell viability assay was used to assess the inhibitory effect of TRAIL on cell growth of HT29 human colorectal cancer cells. And 6-diamidino-2-phenylindole(DAPI), terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay(TUNEL) staining assay were used to evaluate cell-apoptosis. Western blot analysis were conducted to observe apoptosis related proteins and death receptor. To assess whether the synergized inhibitory effect of SVT and TRAIL on reactive oxygen species(ROS) generation was reversed by strong anti-oxidative agent. Results : SVT with TRAIL inhibited HT29 cell growth different from TRAIL alone. Consistent with cell growth inhibition, the expression of TRAIL receptors; Expression of death receptor(DR)4 and DR5 was significantly increased and intrinsic pro-apoptotic cleaved caspase-3, -9 was subsequently increased together with increase of Bax/Bcl-2 ratio and extrinsic pro-apototic caspase-8 was also activated. In addition, the expression of anti-apoptotic survival proteins, a marker of TRAIL resistance(eg, cFLIP, survivin, X-linked inhibitor of apoptosis protein(XIAP) and Bcl-2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the ROS scavenger N-acetylcysteine abolished the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the intrinsic pro-apoptotic caspase-3 and-9. Conclusion : The collective results suggest that SVT facilitates TRAIL-induced apoptosis in $HT_{29}$ human epithelial colorectal cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 and consecutive induction of bilateral apoptosis via regulating apoptosis related proteins.

Effects of Resveratrol and trans-3,5,4'-Trimethoxystilbene on Glutamate-Induced Cytotoxicity, Heme Oxygenase-1, and Sirtuin 1 in HT22 Neuronal Cells

  • Kim, Dae-Won;Kim, Young-Mi;Kang, Sung-Don;Han, Young-Min;Pae, Hyun-Ock
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.306-312
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    • 2012
  • Resveratrol (trans-3,5,4'-trihydroxystilbene) has received considerable attention recently for the potential neuroprotective effects in neurodegenerative disorders where heme oxygenase-1 (HO-1) and sirtuin 1 (SIRT1) represent promising therapeutic targets. Resveratrol has been known to increase HO-1 expression and SIRT1 activity. In this study, the effects of resveratrol and trans-3,5,4'-trimethoxystilbene (TMS), a resveratrol derivative, on cytotoxicity caused by glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation have been investigated by using murine hippocampal HT22 cells, which have been widely used as an in vitro model for investigating glutamate-induced neurotoxicity. Resveratrol protected HT22 neuronal cells from glutamate-induced cytotoxicity and increased HO-1 expression as well as SIRT1 activity in a concentration-dependent manner. Cytoprotection afforded by resveratrol was partially reversed by the specific inhibition of HO-1 expression by HO-1 small interfering RNA and the nonspecific blockage of HO-1 activity by tin protoporphyrin IX, but not by SIRT1 inhibitors. Surprisingly, TMS, a resveratrol derivative with methoxyl groups in lieu of the hydroxyl groups, and trans-stilbene, a non-hydroxylated analog, failed to protect HT22 cells from glutamate-induced cytotoxicity and to increase HO-1 expression and SIRT1 activity. Taken together, our findings suggest that the cytoprotective effect of resveratrol was at least in part associated with HO-1 expression but not with SIRT1 activation and, importantly, that the presence of hydroxyl groups on the benzene rings of resveratrol appears to be necessary for cytoprotection against glutamate-induced oxidative stress, HO-1 expression, and SIRT1 activation in HT22 neuronal cells.

Influence of Hold Time and Stress Ratio on Cyclic Creep Properties Under Controlled Tension Loading Cycles of Grade 91 Steel

  • Kim, Woo-Gon;Park, Jae-Young;Ekaputra, I Made Wicaksana;Kim, Seon-Jin;Jang, Jinsung
    • Nuclear Engineering and Technology
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    • v.49 no.3
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    • pp.581-591
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    • 2017
  • Influences of hold time and stress ratio on cyclic creep properties of Grade 91 steel were systemically investigated using a wide range of cyclic creep tests, which were performed with hold times (HTs) of 1 minute, 3 minutes, 5 minutes, 10 minutes, 20 minutes, and 30 minutes and stress ratios (R) of 0.5, 0.8, 0.85, 0.90, and 0.95 under tension loading cycles at $600^{\circ}C$. Under the influence of HT, the rupture time increased to HT = 5 minutes at R = 0.90 and R = 0.95, but there was no influence at R = 0.50, 0.80, and 0.85. The creep rate was constant regardless of an increase in the HT, except for the case of HT = 5 minutes at R = 0.90 and R = 0.95. Under the influence of stress ratio, the rupture time increased with an increase in the stress ratio, but the creep rate decreased. The cyclic creep led to a reduction in the rupture time and an acceleration in the creep rate compared with the case of monotonic creep. Cyclic creep was found to depend dominantly on the stress ratio rather than on the HT. Fracture surfaces displayed transgranular fractures resulting from microvoid coalescence, and the amount of microvoids increased with an increase in the stress ratio. Enhanced coarsening of the precipitates in the cyclic creep test specimens was found under all conditions.

A Study on the Mechanisms by Which the Aqueous Extract of Inonotus obliquus Induces Apoptosis and Inhibits Proliferation in HT-29 Human Colon Cancer Cells (차가버섯 물추출물의 대장암세포 증식억제 및 Apoptosis 유도기전 연구)

  • Kim, Eun-Ji;Lee, Yong-Jin;Shim, Hyun-Kyung;YoonPark, Jung-Han
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.5
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    • pp.516-523
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    • 2006
  • The mushroom Inonotus obliquue (IO) has been traditionally used for the treatment of gastrointestinal cancer in Russia, Poland, and most of Baltic countries. To explore the possibility that IO has chemoprevention effects, we examined whether or not the aqueous extract of IO inhibits HT-29 cell growth and investigated tile mechanism for this effect. Cells were incubated in the presence of increasing concentrations of the aqueous extract of IO. The extract substantially inhibited the viable HT-29 cell number in a dose-dependent manner and inhibited 5-bromo-2'-deoxyuridine incorporation into DNA of HT-29 cells. Annexin-V staining followed by flow cytometry revealed that the extract induced apoptosis of HT-29 cells in a dose-dependent manner. Western blot analysis of total cell lysates revealed that the extract induced cleavage of caspase-8, -9 and -3 and poly (ADP-ribose) polymerase, but did not affect the protein levels of Bax and Bcl-2. In addition, the extract dose-dependently increased the activity of caspase-8, -9 and -3. We have demonstrated that the aqueous extract of IO inhibits cell proliferation and induces apoptosis in HT-29 cells, which may be mediated by its ability to activate the caspase pathway.

Pharmacophore Hypothesis for Atypical Antipsychotics

  • Sekhar, Kondapalli Venkata Gowri Chandra;Vyas, Devambhatla Ravi Kumar;Nagesh, Hunsur Nagendra;Rao, Vajja Sambasiva
    • Bulletin of the Korean Chemical Society
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    • v.33 no.9
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    • pp.2930-2936
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    • 2012
  • A three-dimensional pharmacophore hypothesis was developed for atypical antipsychotics in order to map common structural features of highly active compounds by using HipHop in CATALYST program. The pharmacophore hypotheses were generated using 12 compounds as training set and validated using 11 compounds as test set. The most predictive hypothesis (Hypo1) comprises five features viz. two hydrophobic regions, two hydrogen bond acceptor lipid and one aromatic ring. In the absence of information like crystallized structure of 5-$HT_{2A}$ receptor and binding mode of antipsychotics with 5-$HT_{2A}$ receptor, this hypothesis will serve as a potentially valuable tool in the design of novel atypical antipsychotics acting primarily at 5-$HT_{2A}$ and $D_2$ receptors.