Induction of apoptosis by 6-Methoxydihydrosanguinarine isolated from Hylomecon hylomeconoides

Hu-Quan Yin,Yong-Jin Lee,Hyun-Mi Kim,Young-Ho Kim,Byung-Hoon Lee 대한약학회 2004 大韓藥學會 總會 및 學術大會 Vol.2004 No.1

Temporal Changes in the Hepatic Fatty Liver in Mice Receiving Standard Lieber-DeCarli Diet

Hu-Quan Yin,Byung-Hoon Lee 한국독성학회 2008 Toxicological Research Vol.24 No.2

Chronic exposure to ethanol induces cumulative damage to the liver starting from fatty infiltration to cirrhosis depending on the dose and duration of exposure. The whole process leading to the development of alcoholic liver disease is very complex and the mechanisms involved are not fully understood. Among many experimental animal models, Lieber-DeCarli liquid diet provides moderate to severe pathophysiological outcome depending on the compositional changes. In the present study, we investigated the temporal changes in the early phase hepatic disease in rats fed with standard Lieber-DeCarli diet. Male Wistar rats were fed with Lieber-Decarli ethanol diet for 6 weeks and the liver samples were obtained after 2, 4 and 6 weeks. Mild fatty infiltration was observed in 2 weeks of feeding and it became evident in 4 and 6 week samples. The level of hepatic triglyceride showed a good agreement with the data obtained in the pathological analysis. Feeding mice with ethanol diet resulted in the maturation and translocation of SREBP-1 to nucleus in the liver. Western blot analysis of the pooled liver sample of control and ethanol fed animals showed a clear-cut time-dependent increase in the expression of nSREBP-1. These data provide important information for selecting proper time point in experimental intervention study in the field of drug development for alcoholic liver disease.

Temporal Changes in the Hepatic Fatty Liver in Mice Receiving Standard Lieber-DeCarli Diet

Yin, Hu-Quan,Lee, Byung-Hoon Korean Society of ToxicologyKorea Environmental Mu 2008 Toxicological Research Vol.25 No.3

Chronic exposure to ethanol induces cumulative damage to the liver starting from fatty infiltration to cirrhosis depending on the dose and duration of exposure. The whole process leading to the development of alcoholic liver disease is very complex and the mechanisms involved are not fully understood. Among many experimental animal models, Lieber-DeCarli liquid diet provides moderate to severe pathophysiological outcome depending on the compositional changes. In the present study, we investigated the temporal changes in the early phase hepatic disease in rats fed with standard Lieber-DeCarli diet. Male Wistar rats were fed with Lieber-Decarli ethanol diet for 6 weeks and the liver samples were obtained after 2, 4 and 6 weeks. Mild fatty infiltration was observed in 2 weeks of feeding and it became evident in 4 and 6 week samples. The level of hepatic triglyceride showed a good agreement with the data obtained in the pathological analysis. Feeding mice with ethanol diet resulted in the maturation and translocation of SREBP-1 to nucleus in the liver. Western blot analysis of the pooled liver sample of control and ethanol fed animals showed a clear-cut time-dependent increase in the expression of nSREBP-1. These data provide important information for selecting proper time point in experimental intervention study in the field of drug development for alcoholic liver disease.

Induction of the Anticarcinogenic Marker Enzyme, Quinone Reductase, by Dalbergiae Lignum

Yin, Hu-Quan,Lee, Bang-Wool,Kim, Youn-Chul,Sohn, Dong-Hwan,Lee, Byung-Hoon The Pharmaceutical Society of Korea 2004 Archives of Pharmacal Research Vol.27 No.9

The effect of an extract of Dalbergiae Lignum and four components that were isolated from the extract on the anticarcinogenic phase II marker enzyme, quinone reductase (QR), was investi-gated. Of the solvent extracts of Dalbergiae Lignum, the CH$_2$CI$_2$ fraction was the most potent in inducing QR activity, with a CD value (the concentration required to double the QR activity) of 29.5 $\mu$/mL. The CH$_2$CI$_2$ extract was further separated into six compounds, four of which were identified as 4-methoxydalbergione, latifolin, 4',6-dihydroxy-7-methoxyflavanone, and obtusafu-ran. Obtusafuran [CD = 1.1 $\mu$M; chemopreventive index (CI) = 101.9] and latifolin (CD = 1.7 $\mu$M; CI = 154.6) displayed potent QR inducing activity and high chemopreventive indices. Lati-folin and 4-methoxydalbergione were identified as strong DPPH-scavengers with half-maximal free radical scavenging concentrations of 15.9 and 17.2 $\mu$M, respectively.

Effects of Tanshinone IIA on the Hepatotoxicity and Gene Expression Involved in Alcoholic Liver Disease

Yin, Hu-Quan,Kim, Youn-Su,Choi, You-Jin,Kim, Youn-Chul,Sohn, Dong-Hwan,Ryu, Shi-Yong,Lee, Byung-Hoon 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.5

Tanshinone IIA is one of the most abundant constituents of the root of Salvia miltiorrhiza BUNGE which exerts antioxidant and anti-inflammatory actions in many experimental disease models. In the present study, we demonstrated that the standardized fraction of S. miltiorrhiza (Sm-SF) was able to protect RAW 264.7 cells from ethanol- and lipopolysaccharide (LPS)- induced production of superoxide radical, activation of NADPH oxidase and subsequently death of the cells. Among four main components of Sm-SF, tanshinone IIA was the most potent in protecting cells from LPS-and ethanol-induced cytotoxicity. LPS or ethanol induced the expression of CD14, iNOS, and SCD1 and decreased RXR-$\alpha$, which was completely reversed by tanshinone IIA. In H4IIEC3 cells, $10\;{\mu}M$ tanshinone IIA effectively blocked ethanolinduced fat accumulation as evidenced by Nile Red binding assay. These results indicate that tanshinone IIA may have potential to inhibit alcoholic liver disease by reducing LPS- and ethanol-induced Kupffer cell sensitization, inhibiting synthesis of reactive oxygen/nitrogen species, inhibiting fatty acid synthesis and stimulating fatty acid oxidation.

Effects of Tanshinone IIA on the Hepatotoxicity and Gene Expression Involved in Alcoholic Liver Disease

Hu-Quan Yin,Youn-Su Kim,You-Jin Choi,김윤철,손동환,Shi-Yong Ryu,이병훈 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.5

Tanshinone IIA is one of the most abundant constituents of the root of Salvia miltiorrhiza BUNGE which exerts antioxidant and anti-inflammatory actions in many experimental disease models. In the present study, we demonstrated that the standardized fraction of S. miltiorrhiza (Sm-SF) was able to protect RAW 264.7 cells from ethanol- and lipopolysaccharide (LPS)- induced production of superoxide radical, activation of NADPH oxidase and subsequently death of the cells. Among four main components of Sm-SF, tanshinone IIA was the most potent in protecting cells from LPS-and ethanol-induced cytotoxicity. LPS or ethanol induced the expression of CD14, iNOS, and SCD1 and decreased RXR-α, which was completely reversed by tanshinone IIA. In H4IIEC3 cells, 10 μM tanshinone IIA effectively blocked ethanolinduced fat accumulation as evidenced by Nile Red binding assay. These results indicate that tanshinone IIA may have potential to inhibit alcoholic liver disease by reducing LPS- and ethanol- induced Kupffer cell sensitization, inhibiting synthesis of reactive oxygen/nitrogen species, inhibiting fatty acid synthesis and stimulating fatty acid oxidation.

Role of the Fas/Fas Ligand Death Receptor Pathway in Ginseng Saponin Metabolite-Induced Apoptosis in HepG2 Cells

오선희,Hu-Quan Yin,Byung-Hoon Lee 대한약학회 2004 Archives of Pharmacal Research Vol.27 No.4

Gene Expression Analysis of So Called Asian Dust Extracts in Human Acute Myeloid Leukemia Cells

You-Jin Choi,Hu-Quan Yin,Eun-Jung Park,Kwangsik Park,Dae-Seon Kim,Byung-Hoon Lee 한국독성학회 2010 Toxicological Research Vol.26 No.1

As the frequency and the intensity of so called Asian dust (AD) events have increased, public concerns about the adverse health effects has spiked sharply over the last two decades. Despite the recent reports on the correlation between AD events and the risk for cardiovascular and respiratory disease, the nature of the toxicity and the degree of the risk are yet largely unknown. In the present study, we investigated the effects of the dichloromethane extract of AD (AD-X) and that of urban dust (NAD-X) collected during a non-AD period on gene expression in HL-60 cells using Illumina Sentrix HumanRef-8 Expression BeadChips. Global changes in gene expression were analyzed after 24 h of incubation with 50 or 100 ㎍/㎖ AD-X and NAD-X. By one-way analysis of variance (p < 0.05) and Benjamini-Hochberg multiple testing correction for false discovery rate of the results, 573 and 297 genes were identified as AD-X- and NAD-X-responsive, respectively. The genes were classified into three groups by Venn diagram analysis of their expression profile, i.e., 290 AD-X-specific, 14 NAD-X-specific, and 283 overlapping genes. Quantitative realtime PCR confirmed the changes in the expression levels of the selected genes. The expression patterns of five genes, namely SORL1, RABEPK, DDIT4, AZU1, and NUDT1 differed significantly between the two groups. Following rigorous validation process, these genes may provide information in developing biomarker for AD exposure.

Apoptosis Inducing Effects of 6-Methoxydihydrosanguinarine in HT29 Colon Carcinoma Cells

Yong-Jin Lee,Hu-Quan Yin,Young-Ho Kim,Guang-Yong Li,Byung-Hoon Lee 대한약학회 2004 Archives of Pharmacal Research Vol.27 No.12

6-Methoxydihydrosanguinarine (6ME), a benzophenanthridine alkaloid derived from the methanol extracts of Hylomecon hylomeconoides, showed a dose-dependent effect at 1-10 μM on causing apoptotic cell death in HT29 colon carcinoma cells (IC50 = 5.0 ± 0.2 μM). Treatment of HT-29 cells with 6ME resulted in the formation of internucleosomal DNA fragmentation. Treatment of the cells with 6ME caused activation of caspase-3, -8 and 9 protease and subsequent proteolytic cleavage of poly(ADP-ribose)polymerase. 6ME increased the expression of p53 and Bax and decreased the expression of Bid. These results indicate that p53 and proapoptotic Bcl-2 family proteins might participate in the antiproliferative activity of 6ME in HT29 cells.

Gene Expression Analysis of So Called Asian Dust Extracts in Human Acute Myeloid Leukemia Cells

Choi, You-Jin,Yin, Hu-Quan,Park, Eun-Jung,Park, Kwang-Sik,Kim, Dae-Seon,Lee, Byung-Hoon Korean Society of ToxicologyKorea Environmental Mu 2010 Toxicological Research Vol.27 No.1

As the frequency and the intensity of so called Asian dust (AD) events have increased, public concerns about the adverse health effects has spiked sharply over the last two decades. Despite the recent reports on the correlation between AD events and the risk for cardiovascular and respiratory disease, the nature of the toxicity and the degree of the risk are yet largely unknown. In the present study, we investigated the effects of the dichloromethane extract of AD (AD-X) and that of urban dust (NAD-X) collected during a non-AD period on gene expression in HL-60 cells using Illumina Sentrix HumanRef-8 Expression BeadChips. Global changes in gene expression were analyzed after 24 h of incubation with 50 or 100 ${\mu}g$/ml AD-X and NAD-X. By one-way analysis of variance (p < 0.05) and Benjamini-Hochberg multiple testing correction for false discovery rate of the results, 573 and 297 genes were identified as AD-X- and NAD-X-responsive, respectively. The genes were classified into three groups by Venn diagram analysis of their expression profile, i.e., 290 AD-X-specific, 14 NAD-X-specific, and 283 overlapping genes. Quantitative realtime PCR confirmed the changes in the expression levels of the selected genes. The expression patterns of five genes, namely SORL1, RABEPK, DDIT4, AZU1, and NUDT1 differed significantly between the two groups. Following rigorous validation process, these genes may provide information in developing biomarker for AD exposure.