Suppression of peroxisome proliferator-activated receptor gamma-coactivator-1alpha normalizes the glucolipotoxicity-induced decreased BETA2/NeuroD gene transcription and improved glucose tolerance in diabetic rats.

Kim, Ji-Won,You, Young-Hye,Ham, Dong-Sik,Cho, Jae-Hyoung,Ko, Seung-Hyun,Song, Ki-Ho,Son, Ho-Young,Suh-Kim, Haeyoung,Lee, In-Kyu,Yoon, Kun-Ho Association for the Study of Internal Secretions 2009 Endocrinology Vol.150 No.9

<P>Peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1alpha) is significantly elevated in the islets of animal models of diabetes. However, the molecular mechanism has not been clarified. We investigated whether the suppression of PGC-1alpha expression protects against beta-cell dysfunction in vivo and determined the mechanism of action of PGC-1alpha in beta-cells. The studies were performed in glucolipotixicity-induced primary rat islets and INS-1 cells. In vitro and in vivo approaches using adenoviruses were used to evaluate the role of PGC-1alpha in glucolipotoxicity-associated beta-cell dysfunction. The expression of PGC-1alpha in cultured beta-cells increased gradually with glucolipotoxicity. The overexpression of PGC-1alpha also suppressed the expression of the insulin and beta-cell E-box transcription factor (BETA2/NeuroD) genes, which was reversed by PGC-1alpha small interfering RNA (siRNA). BETA2/NeuroD, p300-enhanced BETA2/NeuroD, and insulin transcriptional activities were significantly suppressed by Ad-PGC-1alpha but were rescued by Ad-siPGC-1alpha. PGC-1alpha binding at the glucocorticoid receptor site on the BETA2/NeuroD promoter increased in the presence of PGC-1alpha. Ad-siPGC-1alpha injection through the celiac arteries of 90% pancreatectomized diabetic rats improved their glucose tolerance and maintained their fasting insulin levels. The suppression of PGC-1alpha expression protects the glucolipotoxicity-induced beta-cell dysfunction in vivo and in vitro. A better understanding of the functions of molecules such as PGC-1alpha, which play key roles in intracellular fuel regulation, could herald a new era of the treatment of patients with type 2 diabetes mellitus by providing protection from glucolipotoxicity, which is an important cause of the development and progression of the disease.</P>

Urtica thunbergiana의 생리활성 : The Effects of the Antivities in the Streptozotocin-induced Hyperglycimic Rats Streptozotocin 유발 고혈당 흰쥐에 대한 항당뇨 효과

함인혜,김일혁 중앙대학교 약학연구소 1990 약학 논총 Vol.4 No.-

To elucidate the effects of Urtica thunbergiana on streptozotocin-induced hyperglycemia, U. thunbergiana extracts were administered before and after injection of streptozotocin (45mg / kg, i.p.), and blood glucose, serum triglyceride and serum cholesterol levles were determined at 4 days after streptozotocin injection. The results were as following; 1. The blood glucose levels of streptozotocin-induced hyperglycemic rats were significantly decreased by the administrations by all of the various fractions of U. thrnbergiana and methanol extracts of herb parts were showed dose-dependently. 2. The serum total cholesterol levels were decreased by the administrations by all of the various fractions of U. thunbergiana and methanol extracts and butanol extracts of herb parts were showed dose-dependently. 3. The serum triglyceride levels decreased significantly all of the various fractions of U. thunbergiana.

왕가시오가피나무 잎의 성분

박유선,함인혜,황완균 중앙대학교 약학연구소 1997 약학 논총 Vol.11 No.-

Constituents from the leaves of Acanthopanax senticosus var. Koreanus(Araliaceae), a plant origin of Acanthopanax senticosi Cortex which has been used as tonic, stress-relaxing agent, antidiabetes, antirheumatic, etc. in Korean folk medicine were isolated. The methanolic extracts of dried leaves of Acanthopanax senticosus var. Koreanus was suspended in ether to remove fatty substances. The aqueous fraction was further seperated by Amberlite XAD-2 column employing gradient solvent systems(H_2O, 20, 40, 60, 100% MeOH). By successive column chromatography using sephadex LH-20, ODS and polasil gel. Compound Ⅰ and Cpmpound Ⅱ, were isolated from the 40% MeOH fraction. Chemical structures of Compound Ⅰ and Ⅱ were identified as chiisanoside, and quercetin-3-β-D-galactopyranoside respectively on the basis of physico-chemical and spectral data of IR, FAB-MS, ^1H-NMR, ^13C-NMR, ^1H-^1H COSY, ^13C-^1H COSY and HMBC(^1H-Derected Multiple-bonded Heteronuclear quantum Coherence spectrum).

Antioxidative Compounds from Quercus salicina Blume Stem

Jung-il Kim,Sungun Kim,Kyoung-tae Lee,In-hye Ham1,Ho-hyun Kim,Wan-Kyunn Whang 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.3

The chromatographic separation of MeOH extract from the Quercus salicina Blume Stem led to the isolation of five phenolic compounds. Using spectroscopic methods, the structures of these compounds were determined as D-threo-guaiacylglycerol 8-O- β-D-(6'-O-galloyl)glucopyranoside (1), 9-methoxy-D-threo-guaiacylglycerol 8-O- β-D-(6'-O-galloyl)glucopyranoside (2), 6"-O-galloyl salidroside (3), methyl gallate (4), quercetin (5). We measured radical scavenging activity with the DPPH method and the anti-lipid peroxidative efficacy on human LDL with TBARS assay, with the result that all these compounds exhibited the antioxidative activity.

Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target

HUR, HOON,XUAN, YI,KIM, YOUNG BAE,LEE, GWANG,SHIM, WOOYOUNG,YUN, JISOO,HAM, IN-HYE,HAN, SANG-UK D.A. Spandidos 2013 International journal of oncology Vol.42 No.1

<P>In contrast to mitochondria in healthy cells, which utilize oxidative phosphorylation, malignant cells undergo elevated glycolysis for energy production using glucose. The objectives of this study were to evaluate whether the expression of various molecules, including pyruvate dehydrogenase kinase-1 (PDK-1), is involved in the altered glucose metabolism associated with gastric cancer prognosis and to assess the role of a therapeutic agent in targeting glucose metabolism in gastric cancer. Immunohistochemistry was performed on gastric cancer tissues obtained from 152 patients who underwent curative resection to assess the expression of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), hexokinase-2 (HK-2) and PDK-1. In an <I>in vitro</I> analysis, the lactate production and glucose uptake levels, cellular viability and 5-fluorouracil (5-FU) responses were evaluated before and after treatment with dichloroacetate (DCA), a PDK-1 inhibitor, in the MKN45 and AGS gastric cancer cell lines and in the non-cancerous HEK293 cell line. GLUT-1 and PDK-1 expression was significantly associated with tumor progression, although only PDK-1 expression was an independent prognostic factor for patients who received 5-FU adjuvant treatment. There was no significant difference in cell viability between the HEK293 and gastric cancer cell lines following DCA treatment. However, DCA treatment reduced lactate production and increased responsiveness to 5-FU in MKN45 cells, which expressed high levels of PDK-1 in comparison to the other cell lines. Thus, PDK-1 may serve as a biomarker of poor prognosis in patients with gastric cancer. In addition, PDK-1 inhibitors such as DCA may be considered an additional treatment option for patients with PDK-1-expressing gastric cancers.</P>

Inhibition of Discoidin Domain Receptor 1 Prevents Stroma-Induced Peritoneal Metastasis in Gastric Carcinoma

Jin, Hyejin,Ham, In-Hye,Oh, Hye Jeong,Bae, Cheong A,Lee, Dakeun,Kim, Young-Bae,Son, Sang-Yong,Chwae, Yong-Joon,Han, Sang-Uk,Brekken, Rolf A.,Hur, Hoon American Association for Cancer Research 2018 Molecular Cancer Research Vol.16 No.10

<P>Discoidin domain receptor 1 (DDR1) is activated by fibrillar (triple-helical) collagens and collagen IV, which are major components of tumor stroma; thus, DDR1 might be a critical mediator of communication between cancer cells and stroma. The aim of this study was to investigate the effect of DDR1 inhibition on stroma-induced peritoneal metastasis in gastric carcinoma. We analyzed by immunohistochemistry the correlation between DDR1 expression and the pattern of recurrence in gastric carcinoma tissues from a previously characterized and established gastric carcinoma patient cohort. We also cocultured human gastric carcinoma cell lines with gastric cancer–associated fibroblasts (CAF) and investigated DDR1 expression and activation. We evaluated CAF-induced tumorigenic properties of gastric carcinoma cell lines and the effect of a DDR1-specific inhibitor in organotypic cultures and in a peritoneal seeding xenograft animal model. The expression of DDR1 in gastric cancer tissues was positively associated with early recurrence (<I>P</I> = 0.043) and a high incidence of peritoneal recurrence (<I>P</I> = 0.036). We confirmed that coculturing with CAFs elevated DDR1 protein expression in gastric carcinoma cell lines and enhanced gastric carcinoma cell line spheroid formation in organotypic cultures in a tumor cell DDR1-dependent manner. Coimplantation of CAFs with gastric carcinoma cells enhanced peritoneal tumor formation <I>in vivo</I>, an effect that was sensitive to pharmacologic inhibition of DDR1.</P><P><B>Implications:</B> This study highlights that CAF-induced elevation of DDR1 expression in gastric carcinoma cells enhances peritoneal tumorigenesis, and that inhibition of DDR1 is an attractive strategy for the treatment of gastric carcinoma peritoneal metastasis. <I>Mol Cancer Res; 16(10); 1590–600. ©2018 AACR</I>.</P>

Control effects of Frankliniella occidentalis by trap plant and natural enemy(Orius laevigatus) in Chrysanthemum Polyvinyl Houses

Yong Seok Choi,In Su Hwang,Jun Seok Lee,Eun Hye Ham,Deog Kee Park 한국응용곤충학회 2013 한국응용곤충학회 학술대회논문집 Vol.2013 No.10

F. occidentalis causes to decrease the yield of chrysanthemum flower economically because it is the major crop pest injuring the flower directly at flowering period in chrysanthemum artificial houses. The control of it with chemicals is very difficult because the resistance of it to chemicals is so high. F. occidentalis began to occur at early-May and increased rapidly mid-May after in standard chrysanthemum artificial houses, Yesan, Chungcheongnam-do. In case of a farm, the density of it increased continuously in spite of chemical control . The times of chemical control to depress the density of it was 6 or 7th for cultivation period of chrysanthemum. We put the flowering yellow pot-mum already (trap plant attracting F. occidentalis) in standard chrysanthemum PVC-houses and set the yellow sticky cards up at an interval of 5m from trap plant(TP). The more yellow sticky trap near to trap plant, the more F. occidentalis was attracted to yellow sticky trap. TP was more attractive to adult F. occidentalis up to distances of 10m. The numbers of it attracted to yellow sticky traps at different distance from TP was not different significantly when standard chrysanthemum bloomed. We put the TP in standard chrysanthumum PVC-house at an distance of 20m and released the natural enemies (Orius laevigatus) on TP at 3 times, an interval of 7 days. And then we set yellow sticky traps up at an distance of 5m from TP and compared the plot with TP+natural enemy(NE) to the plot without them. The density of F. occidentalis was rather lower at TP+NE plot than the plot without at the formative period of flower bud of standard chrysanthemum. Therefore, The yellow flowering chrysanthemum possesses great value of TP attracting F. occidentalis in chrysanthumum PVC-house up to flowering period of cultivating chrysanthemum, and if it is used with natural enemy and chemicals simultaneously, farmers can minimize the quantity of chemicals used.

국내 종대황 (種大黃)의 기원과 분류

Ae Kyung Kim,Han Na Choi,Bum Jung Kim,In Hye Ham,So Min Lee,Cheol Min Jo,Kyung Jin Lee,Ho Young Choi 한국약용작물학회 2017 한국약용작물학술대회 발표집 Vol.2017 No.05

Background : Undulatum Rhubarb, commonly produced in domestic, is rhizome of Rheum undulatum L. that belongs to the family Polygonaceae. It also can be used as a substitute of R. palmatum L., R. tanguticum Maximowicz ex Balf., and R. officinale Baillon which completely depend on import system. However, there should be clear clarification among Undulatum Rhubarb and Rhubarb, because Undulatum Rhubarb contains rhaponticin as marker compound that is not indicated at Rhubarb. Some of the recently imported Undulatum Rhubarbs have been found to be Rhubarb. Also, it is known that only Undulatum Rhubarb is cultivated at domestic environment. But some plant origins of Rhubarb are grown in Korea, too. Further study are needed to clarify clear origin between Undulatum Rhubarb and Rhubarb. Thus, we collected some domestically cultivated samples and identified them. Methods and Reseults : Rheum undulatum L., Rhubarb, Rheum tanguticum Maximowicz ex Balf. which were cultivated in Gangwondo Agricultural Research and Extension Services in Cheorwon were collected and anayzed the DNA sequences. We also compared DNA sequences in Rhubarb collected from England and R. rhabarbarum L., R. undulatum L., and R. franzenbachii on NCBI. As a result, two kinds of rhubarb cultivated in the test plantation were identified as R. rhabarbarum and R. officinale. In addition, R. undulatum (plant origin of Undulatum Rhubarb) was identified as Rhubarb (Rheum rhabarbarum) in England with 99 - 100% identical in nuclear ITS gene region. Conclusion : R. undulatum, plant origin of Undulatum Rhubarb, is reported as synonym of R. rhabarbarum, R. franzenbachii. Rheum speices which are cultivated as tester in Gangwondo Agricultural Research and Extension Services in Cheorwon are estimated as R. undulatum and R. officinale. Therefore, not only Undulatum Rhubarb but Rhubarb could be grown in Korea.

소화기 질환 동물모델에서 평위산(平胃散)의 염증 완화 효과

정세영 ( Seyoung Jung ),정성은 ( Sung Eun Jung ),김지혜 ( Ji Hye Kim ),함성호 ( Seong Ho Ham ),양웅모 ( Woong Mo Yang ),권보인 ( Bo-in Kwon ) 대한본초학회 2020 大韓本草學會誌 Vol.35 No.2

Objectives : Pyeongwi-san is widely used in Korean medicine for acute indigestion or gastrodynia. As a therapeutic agent for digestive diseases of modern people, in order to confirm the mechanism of Pyeongwi-san on digestive tract disease and the difference of therapeutic efficacy between its formulation, a comparative efficacy test was conducted on digestive tract disease animal model. Methods : For LPS enteritis animal model, male SD rats were intraorally treated with different formulation types of Pyeongwi-san, and then intraperitoneally administered LPS one hour later to induce enteritis. After 5 hours, blood was collected and TNFα, IL-1β, IL-6 and PGE2 were confirmed by ELISA. For acute gastritis animal model, male SD rats were intraorally treated with different formulation types of Pyeongwi-san according to the prescribed concentration, and then intraorally administered 60% ethanol and 150 mM HCl one hour later to induce acute gastritis. After 5 hours, blood was collected and TNFα ,IL-6 were confirmed by ELISA. Results : In the LPS-administered enteritis animal model, Pyeongwi-san decreased TNFα, IL-1β, PGE2 and especially IL-6. Pyeongwi-san also decreased IL-6 in acute gastritis animal model. In addition, there was no significant difference in efficacy between the two formulations when compared with inflammatory markers. Conclusions : The efficacy of Pyeongwi-san was confirmed in the inflammatory markers related to digestive inflammatory diseases, and the efficay between two formulations of Pyeongwi-san was relatively similar. Further studies are needed to investigate the new applicability of Pyeongwi-san on different inflammatory diseases that have similar inflammation markers identified in this experiment.

생약의 표준화에 관한연구(Ⅳ) : 후박, 창출 및 백출의 표준화에 관한 연구 Studies on the standardization of Magnoliae cortex, Atractylodes rhizoma and Atractylodes rhizoma white

조정희,강신복,김혜수,김영림,오미현,강인호,박성수,심영훈,지선경,함일권,하광원,김영중,박만기 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-

후박』창출 및 백출은 건위제로서 널리 사용되는생약이고,대한악전 7개정에서 모두 기원식물과 이화학적인 실험항목이 겔정됨으로서 윤통생딱의 품질확보가요청되고 있다. 이에 본 연구에서는각각 생약의 국내유통품 30여종, 일본약국방품, 중국유통품을 확보하여 꽉인, 함량 및 순도시험을 실시하여 이들 생약을 규격화하고자 하였다. 후박의 함량시험결과 magnelol의 경우 대부분 약전기준인 0-8% 미만이었으며,조선후박인 machilus thunbergii가 아직도 유통됨으로써 약효와 품질에 문제점을 가지고 있었다. 백출의 확인 및 순도시험에서 국내유통품 30종 묘두 적합하였고, 창출의 확인 및 순도시험을 실시한 결과 국내 창출유통품 32종중 11종롸 일본약전품 2종만 창출로 판명되었다. 후박을 함유하는 엑스레제의 경우 처방에 따라 magnolol은 2.t~23.3%, honokiol은 2.6~26-8%코 나타났으턱, 백출함유제제에서는 atractylenolide 111는 46.S~76.3%, atractylon은 12.2~17.2%를 창출함유제제에서는 atractylen III만이 5.7~20.1%를 나타내었다. 춘박, 창출 및 백출의 운통품에 대해서 중금속과 잔류농약둥의 유해물질을 분석한 결고 일부에 잔류농약이 검출되었지만 현 기준께는 적합하였다. 대부분의 생약이 거의 수입되어 국내 유통되므로안전성 및 품질관리 차원에서 꾸준한 연구검토가 이루어져야될 것으로 사료된다. This study was carried out for the standardization and quality control of Magnoliae Cortex, Atractylodes Rhizoma and Atractylodes Rhizoma White. The contents of magnolol in Magnoliae Cortex are not more than 0.,8% criterion established in KP. Machilus thunbergci is still circulated as Magnoliae Cortex instead of Magnolia species. So there has been some problems in efficiency and quality control. The contents of atractylenolide ]f were 0.04―0.45% for Atractylodes Rhizoma White and they were all suitable for identification and purity test. In the case of Atractylodes Rhizoma, only 11 samples were suitable for identification and purity test in 32 species circulated in Korea. This method was used in determination of each component in crude drug preparations containing Magnoliae Cortex, Atractylodes Rhizoma and Atractylodes Rhizoma White. The availability of magnolol in the decoction process was 2.1―23.3%, that of honokiol was 2.6―26.8%. The availability of atractylenolide If in the decoction process was 46.5―76.3% for Atractylodes Rhizoma White and 5.7―20.0% for Atractylodes Rhizoma, that of atractylon was 12.217.2% for Atractylodes Rhizoma White. We also analysed pesticide residue and heavy metal for the circulated crude drug and found that all of them were safe.