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Xijun Wang - One of the best experts on this subject based on the ideXlab platform.
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Insight into the metabolic mechanism of Scoparone on biomarkers for inhibiting Yanghuang syndrome
Scientific reports, 2016Co-Authors: Heng Fang, Aihua Zhang, Hui Sun, Liang Wang, Chang Liu, Xiaohang Zhou, Qi Song, Xijun WangAbstract:Scoparone (6,7-dimethoxycoumarin) is the representative ingredient of Yinchenhao (Artemisia capillaris Thunb.) which is a famous Chinese medicinal herb and shows favorable efficacy for all kinds of liver disease, specifically for the treatment of Yanghuang syndrome (YHS). The precise molecular mechanism concerning the action of Scoparone on YHS is yet to be fully elucidated. The aim of the present study was to determine the mechanism of Scoparone and evaluate its efficacy on metabolite levels. The differential expression of metabolites responsible for the pharmacological effects of Scoparone was characterized and the protection effect of Scoparone against this disease. Using multivariate statistical analysis, 33 biomarkers were identified using precise MS/MS and play an important role in the regulation of key metabolic pathways associated with liver disease. In addition, pathological results also showed consistent changes in the YHS model group and after treatment with Scoparone, both the metabolic profile and histopathology resembled that of normal level, which suggesting favorable efficacy over the observed time period. The present work indicated that a metabolomics platform provided a new insight into understanding the mechanisms of action of natural medicines such as Scoparone.
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Scoparone affects lipid metabolism in primary hepatocytes using lipidomics
Scientific reports, 2016Co-Authors: Aihua Zhang, Hui Sun, Shi Qiu, Tianlei Zhang, Yu Guan, Ying Han, Guangli Yan, Xijun WangAbstract:Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after Scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of Scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of Scoparone on lipid metabolism in hepatocytes. The most striking finding was that Scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in Scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by Scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics.
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Urinary metabolic profiling of rat models revealed protective function of Scoparone against alcohol induced hepatotoxicity
Scientific reports, 2014Co-Authors: Aihua Zhang, Hui Sun, Xijun WangAbstract:Alcohol-induced liver disease (ALD) is a leading cause of non-accident-related deaths in the world. Identification of an early specific signature of ALD would aid in therapeutic intervention. Scoparone is an important constituent of Yinchenhao, and displayed bright prospects in hepatoprotective effect. However, its precise molecular mechanism has not been well explored. The present study was designed to assess the effects and possible mechanisms of Scoparone against alcohol-induced liver injury. UPLC/ESI-Q-TOF/MS combined with pattern recognition approaches including PCA, and PLS-DA were integrated to get differentiating metabolites for the pathways and clarify mechanisms of disease, highlight insights into drug discovery. The results indicated four ions in the positive mode were characterized as potential differentiating metabolites which can be regulated by Scoparone treatment, and suggested that therapeutic effect of Scoparone could regulated the dysfunctions of citrate cycle, sphingolipid metabolism, taurine and hypotaurine.
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proteomics analysis of hepatoprotective effects for Scoparone using maldi tof tof mass spectrometry with bioinformatics
Omics A Journal of Integrative Biology, 2013Co-Authors: Aihua Zhang, Hui Sun, Wenjun Sun, Ye Yuan, Xijun WangAbstract:Abstract Scoparone is an active ingredient of Yinchenhao (Artemisia annua L.), a well-known Chinese medicinal plant, and has been utilized in prevention and therapy of liver damage. However, the molecular drug targets associated with the pharmacological effects of Scoparone are largely unknown. In the present article, we extend the previous research on Yinchenhao through a study of its active ingredient and thus the putative targets of Scoparone. We employed two-dimensional gel electrophoresis, and all proteins expressed were identified by MALDI-TOF/TOF MS and database research. Protein-interacting networks and pathways were also mapped and evaluated. The possible protein network associated with Scoparone was constructed, and contribution of these proteins to the protective effect of Scoparone against the carbon tetrachloride-induced acute liver injury in rats are discussed herein. Hepatoprotective effects of Scoparone on liver injury in rats were associated with regulated expression of six proteins which...
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Proteomics Analysis of Hepatoprotective Effects for Scoparone Using MALDI-TOF/TOF Mass Spectrometry with Bioinformatics
Omics : a journal of integrative biology, 2013Co-Authors: Aihua Zhang, Hui Sun, Wenjun Sun, Ye Yuan, Xijun WangAbstract:Abstract Scoparone is an active ingredient of Yinchenhao (Artemisia annua L.), a well-known Chinese medicinal plant, and has been utilized in prevention and therapy of liver damage. However, the molecular drug targets associated with the pharmacological effects of Scoparone are largely unknown. In the present article, we extend the previous research on Yinchenhao through a study of its active ingredient and thus the putative targets of Scoparone. We employed two-dimensional gel electrophoresis, and all proteins expressed were identified by MALDI-TOF/TOF MS and database research. Protein-interacting networks and pathways were also mapped and evaluated. The possible protein network associated with Scoparone was constructed, and contribution of these proteins to the protective effect of Scoparone against the carbon tetrachloride-induced acute liver injury in rats are discussed herein. Hepatoprotective effects of Scoparone on liver injury in rats were associated with regulated expression of six proteins which...
Aihua Zhang - One of the best experts on this subject based on the ideXlab platform.
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Insight into the metabolic mechanism of Scoparone on biomarkers for inhibiting Yanghuang syndrome
Scientific reports, 2016Co-Authors: Heng Fang, Aihua Zhang, Hui Sun, Liang Wang, Chang Liu, Xiaohang Zhou, Qi Song, Xijun WangAbstract:Scoparone (6,7-dimethoxycoumarin) is the representative ingredient of Yinchenhao (Artemisia capillaris Thunb.) which is a famous Chinese medicinal herb and shows favorable efficacy for all kinds of liver disease, specifically for the treatment of Yanghuang syndrome (YHS). The precise molecular mechanism concerning the action of Scoparone on YHS is yet to be fully elucidated. The aim of the present study was to determine the mechanism of Scoparone and evaluate its efficacy on metabolite levels. The differential expression of metabolites responsible for the pharmacological effects of Scoparone was characterized and the protection effect of Scoparone against this disease. Using multivariate statistical analysis, 33 biomarkers were identified using precise MS/MS and play an important role in the regulation of key metabolic pathways associated with liver disease. In addition, pathological results also showed consistent changes in the YHS model group and after treatment with Scoparone, both the metabolic profile and histopathology resembled that of normal level, which suggesting favorable efficacy over the observed time period. The present work indicated that a metabolomics platform provided a new insight into understanding the mechanisms of action of natural medicines such as Scoparone.
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Scoparone affects lipid metabolism in primary hepatocytes using lipidomics
Scientific reports, 2016Co-Authors: Aihua Zhang, Hui Sun, Shi Qiu, Tianlei Zhang, Yu Guan, Ying Han, Guangli Yan, Xijun WangAbstract:Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after Scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of Scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of Scoparone on lipid metabolism in hepatocytes. The most striking finding was that Scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in Scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by Scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics.
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Urinary metabolic profiling of rat models revealed protective function of Scoparone against alcohol induced hepatotoxicity
Scientific reports, 2014Co-Authors: Aihua Zhang, Hui Sun, Xijun WangAbstract:Alcohol-induced liver disease (ALD) is a leading cause of non-accident-related deaths in the world. Identification of an early specific signature of ALD would aid in therapeutic intervention. Scoparone is an important constituent of Yinchenhao, and displayed bright prospects in hepatoprotective effect. However, its precise molecular mechanism has not been well explored. The present study was designed to assess the effects and possible mechanisms of Scoparone against alcohol-induced liver injury. UPLC/ESI-Q-TOF/MS combined with pattern recognition approaches including PCA, and PLS-DA were integrated to get differentiating metabolites for the pathways and clarify mechanisms of disease, highlight insights into drug discovery. The results indicated four ions in the positive mode were characterized as potential differentiating metabolites which can be regulated by Scoparone treatment, and suggested that therapeutic effect of Scoparone could regulated the dysfunctions of citrate cycle, sphingolipid metabolism, taurine and hypotaurine.
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proteomics analysis of hepatoprotective effects for Scoparone using maldi tof tof mass spectrometry with bioinformatics
Omics A Journal of Integrative Biology, 2013Co-Authors: Aihua Zhang, Hui Sun, Wenjun Sun, Ye Yuan, Xijun WangAbstract:Abstract Scoparone is an active ingredient of Yinchenhao (Artemisia annua L.), a well-known Chinese medicinal plant, and has been utilized in prevention and therapy of liver damage. However, the molecular drug targets associated with the pharmacological effects of Scoparone are largely unknown. In the present article, we extend the previous research on Yinchenhao through a study of its active ingredient and thus the putative targets of Scoparone. We employed two-dimensional gel electrophoresis, and all proteins expressed were identified by MALDI-TOF/TOF MS and database research. Protein-interacting networks and pathways were also mapped and evaluated. The possible protein network associated with Scoparone was constructed, and contribution of these proteins to the protective effect of Scoparone against the carbon tetrachloride-induced acute liver injury in rats are discussed herein. Hepatoprotective effects of Scoparone on liver injury in rats were associated with regulated expression of six proteins which...
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Proteomics Analysis of Hepatoprotective Effects for Scoparone Using MALDI-TOF/TOF Mass Spectrometry with Bioinformatics
Omics : a journal of integrative biology, 2013Co-Authors: Aihua Zhang, Hui Sun, Wenjun Sun, Ye Yuan, Xijun WangAbstract:Abstract Scoparone is an active ingredient of Yinchenhao (Artemisia annua L.), a well-known Chinese medicinal plant, and has been utilized in prevention and therapy of liver damage. However, the molecular drug targets associated with the pharmacological effects of Scoparone are largely unknown. In the present article, we extend the previous research on Yinchenhao through a study of its active ingredient and thus the putative targets of Scoparone. We employed two-dimensional gel electrophoresis, and all proteins expressed were identified by MALDI-TOF/TOF MS and database research. Protein-interacting networks and pathways were also mapped and evaluated. The possible protein network associated with Scoparone was constructed, and contribution of these proteins to the protective effect of Scoparone against the carbon tetrachloride-induced acute liver injury in rats are discussed herein. Hepatoprotective effects of Scoparone on liver injury in rats were associated with regulated expression of six proteins which...
Hui Sun - One of the best experts on this subject based on the ideXlab platform.
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Insight into the metabolic mechanism of Scoparone on biomarkers for inhibiting Yanghuang syndrome
Scientific reports, 2016Co-Authors: Heng Fang, Aihua Zhang, Hui Sun, Liang Wang, Chang Liu, Xiaohang Zhou, Qi Song, Xijun WangAbstract:Scoparone (6,7-dimethoxycoumarin) is the representative ingredient of Yinchenhao (Artemisia capillaris Thunb.) which is a famous Chinese medicinal herb and shows favorable efficacy for all kinds of liver disease, specifically for the treatment of Yanghuang syndrome (YHS). The precise molecular mechanism concerning the action of Scoparone on YHS is yet to be fully elucidated. The aim of the present study was to determine the mechanism of Scoparone and evaluate its efficacy on metabolite levels. The differential expression of metabolites responsible for the pharmacological effects of Scoparone was characterized and the protection effect of Scoparone against this disease. Using multivariate statistical analysis, 33 biomarkers were identified using precise MS/MS and play an important role in the regulation of key metabolic pathways associated with liver disease. In addition, pathological results also showed consistent changes in the YHS model group and after treatment with Scoparone, both the metabolic profile and histopathology resembled that of normal level, which suggesting favorable efficacy over the observed time period. The present work indicated that a metabolomics platform provided a new insight into understanding the mechanisms of action of natural medicines such as Scoparone.
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Scoparone affects lipid metabolism in primary hepatocytes using lipidomics
Scientific reports, 2016Co-Authors: Aihua Zhang, Hui Sun, Shi Qiu, Tianlei Zhang, Yu Guan, Ying Han, Guangli Yan, Xijun WangAbstract:Lipidomics, which focuses on the global study of molecular lipids in biological systems, could provide valuable insights about disease mechanisms. In this study, we present a nontargeted lipidomics strategy to determine cellular lipid alterations after Scoparone exposure in primary hepatocytes. Lipid metabolic profiles were analyzed by high-performance liquid chromatography coupled with time-of-flight mass spectrometry, and a novel imaging TransOmics tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species. Chemometric and statistical analyses of the obtained lipid fingerprints revealed the global lipidomic alterations and tested the therapeutic effects of Scoparone. Identification of ten proposed lipids contributed to the better understanding of the effects of Scoparone on lipid metabolism in hepatocytes. The most striking finding was that Scoparone caused comprehensive lipid changes, as represented by significant changes of the identificated lipids. The levels of identified PG(19:1(9Z)/14:0), PE(17:1(9Z)/0:0), PE(19:1(9Z)/0:0) were found to be upregulated in ethanol-induced group, whereas the levels in Scoparone group were downregulated. Lipid metabolism in primary hepatocytes was changed significantly by Scoparone treatment. We believe that this novel approach could substantially broaden the applications of high mass resolution mass spectrometry for cellular lipidomics.
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Urinary metabolic profiling of rat models revealed protective function of Scoparone against alcohol induced hepatotoxicity
Scientific reports, 2014Co-Authors: Aihua Zhang, Hui Sun, Xijun WangAbstract:Alcohol-induced liver disease (ALD) is a leading cause of non-accident-related deaths in the world. Identification of an early specific signature of ALD would aid in therapeutic intervention. Scoparone is an important constituent of Yinchenhao, and displayed bright prospects in hepatoprotective effect. However, its precise molecular mechanism has not been well explored. The present study was designed to assess the effects and possible mechanisms of Scoparone against alcohol-induced liver injury. UPLC/ESI-Q-TOF/MS combined with pattern recognition approaches including PCA, and PLS-DA were integrated to get differentiating metabolites for the pathways and clarify mechanisms of disease, highlight insights into drug discovery. The results indicated four ions in the positive mode were characterized as potential differentiating metabolites which can be regulated by Scoparone treatment, and suggested that therapeutic effect of Scoparone could regulated the dysfunctions of citrate cycle, sphingolipid metabolism, taurine and hypotaurine.
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proteomics analysis of hepatoprotective effects for Scoparone using maldi tof tof mass spectrometry with bioinformatics
Omics A Journal of Integrative Biology, 2013Co-Authors: Aihua Zhang, Hui Sun, Wenjun Sun, Ye Yuan, Xijun WangAbstract:Abstract Scoparone is an active ingredient of Yinchenhao (Artemisia annua L.), a well-known Chinese medicinal plant, and has been utilized in prevention and therapy of liver damage. However, the molecular drug targets associated with the pharmacological effects of Scoparone are largely unknown. In the present article, we extend the previous research on Yinchenhao through a study of its active ingredient and thus the putative targets of Scoparone. We employed two-dimensional gel electrophoresis, and all proteins expressed were identified by MALDI-TOF/TOF MS and database research. Protein-interacting networks and pathways were also mapped and evaluated. The possible protein network associated with Scoparone was constructed, and contribution of these proteins to the protective effect of Scoparone against the carbon tetrachloride-induced acute liver injury in rats are discussed herein. Hepatoprotective effects of Scoparone on liver injury in rats were associated with regulated expression of six proteins which...
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Proteomics Analysis of Hepatoprotective Effects for Scoparone Using MALDI-TOF/TOF Mass Spectrometry with Bioinformatics
Omics : a journal of integrative biology, 2013Co-Authors: Aihua Zhang, Hui Sun, Wenjun Sun, Ye Yuan, Xijun WangAbstract:Abstract Scoparone is an active ingredient of Yinchenhao (Artemisia annua L.), a well-known Chinese medicinal plant, and has been utilized in prevention and therapy of liver damage. However, the molecular drug targets associated with the pharmacological effects of Scoparone are largely unknown. In the present article, we extend the previous research on Yinchenhao through a study of its active ingredient and thus the putative targets of Scoparone. We employed two-dimensional gel electrophoresis, and all proteins expressed were identified by MALDI-TOF/TOF MS and database research. Protein-interacting networks and pathways were also mapped and evaluated. The possible protein network associated with Scoparone was constructed, and contribution of these proteins to the protective effect of Scoparone against the carbon tetrachloride-induced acute liver injury in rats are discussed herein. Hepatoprotective effects of Scoparone on liver injury in rats were associated with regulated expression of six proteins which...
In-kyu Lee - One of the best experts on this subject based on the ideXlab platform.
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Scoparone interferes with STAT3-induced proliferation of vascular smooth muscle cells
Experimental & molecular medicine, 2015Co-Authors: Sungmi Park, Jeong Kook Kim, Seung Hee Choi, Jae-han Jeon, In-kyu LeeAbstract:Scoparone, which is a major constituent of Artemisia capillaries, has been identified as an anticoagulant, hypolipidemic, vasorelaxant, anti-oxidant and anti-inflammatory drug, and it is used for the traditional treatment of neonatal jaundice. Therefore, we hypothesized that Scoparone could suppress the proliferation of VSMCs by interfering with STAT3 signaling. We found that the proliferation of these cells was significantly attenuated by Scoparone in a dose-dependent manner. Scoparone markedly reduced the serum-stimulated accumulation of cells in the S phase and concomitantly increased the proportion of cells in the G0/G1 phase, which was consistent with the reduced expression of cyclin D1, phosphorylated Rb and survivin in the VSMCs. Cell adhesion markers, such as MCP-1 and ICAM-1, were significantly reduced by Scoparone. Interestingly, this compound attenuated the increase in cyclin D promoter activity by inhibiting the activities of both the WT and active forms of STAT3. Similarly, the expression of a cell proliferation marker induced by PDGF was decreased by Scoparone with no change in the phosphorylation of JAK2 or Src. On the basis of the immunofluorescence staining results, STAT3 proteins phosphorylated by PDGF were predominantly localized to the nucleus and were markedly reduced in the Scoparone-treated cells. In summary, Scoparone blocks the accumulation of STAT3 transported from the cytosol to the nucleus, leading to the suppression of VSMC proliferation through G1 phase arrest and the inhibition of Rb phosphorylation. This activity occurs independent of the form of STAT3 and upstream of kinases, such as Jak and Src, which are correlated with abnormal vascular remodeling due to the presence of an excess of growth factors following vascular injury. These data provide convincing evidence that Scoparone may be a new preventative agent for the treatment of cardiovascular diseases.
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Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity.
PloS one, 2013Co-Authors: Jeong Kook Kim, Joon Young Kim, Han Jong Kim, Keun-gyu Park, Robert A. Harris, Won-jea Cho, Jae Tae Lee, In-kyu LeeAbstract:Scoparone, a natural compound isolated from Artemisia capillaris, has been used in Chinese herbal medicine to treat neonatal jaundice. Signal transducer and activator of transcription 3 (STAT3) contributes to the growth and survival of many human tumors. This study was undertaken to investigate the anti-tumor activity of Scoparone against DU145 prostate cancer cells and to determine whether its effects are mediated by inhibition of STAT3 activity. Scoparone inhibited proliferation of DU145 cells via cell cycle arrest in G1 phase. Transient transfection assays showed that Scoparone repressed both constitutive and IL-6-induced transcriptional activity of STAT3. Western blot and quantitative real-time PCR analyses demonstrated that Scoparone suppressed the transcription of STAT3 target genes such as cyclin D1, c-Myc, survivin, Bcl-2, and Socs3. Consistent with this, Scoparone decreased phosphorylation and nuclear accumulation of STAT3, but did not reduce phosphorylation of janus kinase 2 (JAK2) or Src, the major upstream kinases responsible for STAT3 activation. Moreover, transcriptional activity of a constitutively active mutant of STAT3 (STAT3C) was inhibited by Scoparone, but not by AG490, a JAK2 inhibitor. Furthermore, Scoparone treatment suppressed anchorage-independent growth in soft agar and tumor growth of DU145 xenografts in nude mice, concomitant with a reduction in STAT3 phosphorylation. Computational modeling suggested that Scoparone might bind the SH2 domain of STAT3. Our findings suggest that Scoparone elicits an anti-tumor effect against DU145 prostate cancer cells in part through inhibition of STAT3 activity.
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Scoparone inhibits adipocyte differentiation through down-regulation of peroxisome proliferators-activated receptor γ in 3T3-L1 preadipocytes.
Food chemistry, 2013Co-Authors: Jung-ran Noh, Yong-hoon Kim, Jung Hwan Hwang, Gil-tae Gang, Seung-hoon Yeo, Kyoung-shim Kim, In-kyu Lee, Chul-ho LeeAbstract:This study was performed to investigate the effect of Scoparone on the differentiation of 3T3-L1 preadipocytes. Scoparone inhibited triglyceride (TG) accumulation in the mature adipocytes, evidenced by Oil-red O staining and intracellular quantification. Real time-PCR analysis showed that Scoparone significantly down-regulated the mRNA expression of key adipogenic transcription factors, PPARγ, C/EBPα, compared with mature adipocytes. Scoparone appeared to reduce mRNA expression of SREBP1c and FAS being related to the late stage of adipogenesis. Furthermore, aP2 and CD36/FAT, as adipocyte-specific genes, were decreased in mature adipocytes by Scoparone treatment. Moreover, Scoparone inhibited the up-regulated expression of PPARγ target genes by rosiglitazone to near that observed in cells treated with GW9662. The luciferase assay revealed that Scoparone negatively regulates the transcriptional activity of PPARγ. Chromatin immunoprecipitation assay also showed that participation of Scoparone in the regulation of PPARγ. Collectively, Scoparone has a PPARγ antagonic effect and suppresses differentiation through down-regulation of adipogenic genes by PPARγ inhibition in 3T3-L1 preadipocytes.
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Scoparone suppresses anchorage-independent growth invitro and xenograft tumor growth of DU145 cells in nude mice.
2013Co-Authors: Jeong Kook Kim, Joon Young Kim, Han Jong Kim, Keun-gyu Park, Robert A. Harris, Won-jea Cho, Jae Tae Lee, In-kyu LeeAbstract:A. Scoparone inhibits anchorage-independent growth of DU145 cells. DU145 cells were grown for 3 weeks in 0.25% agarose gel containing vehicle or Scoparone. The number of colonies lager than 2 mm in diameter was counted and data represent the means ± S.E.M. of three independent experiments, each performed in duplicate. *P
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Scoparone suppresses proliferation of DU145 prostate cancer cells by inducing G1-phase cell-cycle arrest.
2013Co-Authors: Jeong Kook Kim, Joon Young Kim, Han Jong Kim, Keun-gyu Park, Robert A. Harris, Won-jea Cho, Jae Tae Lee, In-kyu LeeAbstract:A and B. Scoparone inhibits proliferation of human cancer cell lines. Prostate cancer cells (DU145 and PC-3), RWPE-1 (an immortalized human prostate epithelial cell line), and breast cancer cells (MCF-7 and MDA-MB-231) were serum starved for 24 h. Cells were then incubated in growth medium supplemented with 10% FBS in the presence of vehicle (0.1% DMSO) or the indicated concentrations of Scoparone for 72 h, and cell proliferation was determined by WST-8 assay. Data are expressed as percentages of the vehicle control (defined as 100%) and represent the means ± S.E.M. of three independent experiments, each performed in triplicate. B. Scoparone induces cell-cycle arrest at G1 phase in DU145 cells. Serum-starved DU145 cells were stimulated with 10% FBS in the presence of vehicle or Scoparone (0.5 and 1 mmol/L) for 28 h, and then subjected to flow cytometric analysis of the cell cycle. Bar graph indicates the percentage of cells in G1 phase. The data are the means ± S.E.M. of three independent experiments, each performed in duplicate. *P
Shengliang Xin - One of the best experts on this subject based on the ideXlab platform.
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Scoparone improves hepatic inflammation and autophagy in mice with nonalcoholic steatohepatitis by regulating the ros p38 nrf2 axis and pi3k akt mtor pathway in macrophages
Biomedicine & Pharmacotherapy, 2020Co-Authors: Beibei Liu, Xiaoling Deng, Qianqian Jiang, Junli Zhang, Ning Zhang, Shengliang XinAbstract:Abstract Background and aims Scoparone has been shown to ameliorate many forms of liver disease, and several underlying molecular mechanisms involved have been previously revealed. However, the potential role of Scoparone in autophagy, which is dysregulated in nonalcoholic fatty liver disease-nonalcoholic steatohepatitis (NAFLD-NASH), has not been evaluated. In the current study, we investigated the effect and potential mechanisms of Scoparone in hepatic autophagy in mice with NASH. Methods In vivo, mice were fed a methionine–choline deficient (MCD) diet to establish a NASH model and then subjected to treatment with or without Scoparone for 4 weeks. In vitro, Scoparone was applied in a hepatocellular lipid overload model in AML12 cells challenged with palmitic acid (PA) and in lipopolysaccharide (LPS)-induced RAW264.7 cells. Results Scoparone improved impaired autophagy and several key features of NASH in mice fed an MCD diet. In vitro, Scoparone had an effect on the autophagy of macrophages but not hepatocytes. In RAW264.7 cells, Scoparone reduced the LPS-induced accumulation of autophagosomes and autophagy substrates, the production of reactive oxygen species (ROS) and the inflammatory response. Scoparone inhibited the upregulation of p62 transcription, which is mediated by the ROS/P38/Nrf2 axis. Chloroquine (CQ), an inhibitor of autophagic flux, significantly inhibited Scoparone-mediated protection against inflammation. In addition, Scoparone suppressed activation of the PI3K/AKT/mTOR pathway, and MHY1485 (an mTOR activator that inhibits autophagy) inhibited the anti-inflammatory effect of Scoparone. Conclusions In LPS-induced macrophages, Scoparone regulates autophagy and further suppresses inflammation by inhibiting the ROS/P38/Nrf2 axis and PI3K/AKT/mTOR pathway and enhancing autophagic flux. Scoparone may improve hepatic autophagy and NASH partly through enhancing autophagy in macrophages but not hepatocytes. Scoparone is expected to become a novel therapeutic drug for NASH or diseases associated with dysregulated autophagy in macrophages.
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Scoparone improves hepatic inflammation and autophagy in mice with nonalcoholic steatohepatitis by regulating the ROS/P38/Nrf2 axis and PI3K/AKT/mTOR pathway in macrophages
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2020Co-Authors: Beibei Liu, Xiaoling Deng, Qianqian Jiang, Junli Zhang, Ning Zhang, Shengliang XinAbstract:Abstract Background and aims Scoparone has been shown to ameliorate many forms of liver disease, and several underlying molecular mechanisms involved have been previously revealed. However, the potential role of Scoparone in autophagy, which is dysregulated in nonalcoholic fatty liver disease-nonalcoholic steatohepatitis (NAFLD-NASH), has not been evaluated. In the current study, we investigated the effect and potential mechanisms of Scoparone in hepatic autophagy in mice with NASH. Methods In vivo, mice were fed a methionine–choline deficient (MCD) diet to establish a NASH model and then subjected to treatment with or without Scoparone for 4 weeks. In vitro, Scoparone was applied in a hepatocellular lipid overload model in AML12 cells challenged with palmitic acid (PA) and in lipopolysaccharide (LPS)-induced RAW264.7 cells. Results Scoparone improved impaired autophagy and several key features of NASH in mice fed an MCD diet. In vitro, Scoparone had an effect on the autophagy of macrophages but not hepatocytes. In RAW264.7 cells, Scoparone reduced the LPS-induced accumulation of autophagosomes and autophagy substrates, the production of reactive oxygen species (ROS) and the inflammatory response. Scoparone inhibited the upregulation of p62 transcription, which is mediated by the ROS/P38/Nrf2 axis. Chloroquine (CQ), an inhibitor of autophagic flux, significantly inhibited Scoparone-mediated protection against inflammation. In addition, Scoparone suppressed activation of the PI3K/AKT/mTOR pathway, and MHY1485 (an mTOR activator that inhibits autophagy) inhibited the anti-inflammatory effect of Scoparone. Conclusions In LPS-induced macrophages, Scoparone regulates autophagy and further suppresses inflammation by inhibiting the ROS/P38/Nrf2 axis and PI3K/AKT/mTOR pathway and enhancing autophagic flux. Scoparone may improve hepatic autophagy and NASH partly through enhancing autophagy in macrophages but not hepatocytes. Scoparone is expected to become a novel therapeutic drug for NASH or diseases associated with dysregulated autophagy in macrophages.
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Scoparone alleviates inflammation apoptosis and fibrosis of non alcoholic steatohepatitis by suppressing the tlr4 nf κb signaling pathway in mice
International Immunopharmacology, 2019Co-Authors: Beibei Liu, Xiaoling Deng, Qianqian Jiang, Junli Zhang, Ning Zhang, Shengliang XinAbstract:Scoparone, a naturally-occurring, bioactive compound isolated from the Chinese herb Artemisia capillaria, has been shown to ameliorate hepatotoxicity and cholestasis in liver diseases. However, the pharmacological effect of Scoparone in non-alcoholic steatohepatitis (NASH) has not been elucidated. In this study, we investigated the protective effects and mechanisms of Scoparone in NASH. In vivo, the NASH model was established in mice fed a methionine and choline-deficient (MCD) diet for 4weeks, with or without simultaneous Scoparone treatment. In vitro, RAW264.7 cells induced by lipopolysaccharide (LPS) were pretreated with or without different concentrations of Scoparone. Hepatic triglycerides and serum AST and ALT levels were examined by biochemical assays. Hepatic histology was assessed by H&E, oil red O and Masson's trichrome staining methods, which were applied to analyze the protective effects of Scoparone in NASH. To further explore the underlying mechanism of Scoparone, immunohistochemistry, TUNEL, qRT-PCR, and Western blotting assays were applied to liver tissue or LPS-induced RAW264.7 cells. We found that Scoparone can effectively improve hepatic steatosis, apoptosis, inflammation, and fibrosis in an MCD diet-induced NASH murine model. Mechanistically, we demonstrated that Scoparone treatment alleviates NASH- and lipopolysaccharide (LPS)-induced immune responses in macrophages partly by blocking TLR-4/NF-κB signaling in a dose-dependent manner. Taken together, our results present the potential protective effects and mechanism of Scoparone in NASH, suggesting a potentially beneficial drug treatment for NASH.
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Scoparone alleviates inflammation, apoptosis and fibrosis of non-alcoholic steatohepatitis by suppressing the TLR4/NF-κB signaling pathway in mice.
International immunopharmacology, 2019Co-Authors: Beibei Liu, Xiaoling Deng, Qianqian Jiang, Junli Zhang, Ning Zhang, Shengliang XinAbstract:Scoparone, a naturally-occurring, bioactive compound isolated from the Chinese herb Artemisia capillaria, has been shown to ameliorate hepatotoxicity and cholestasis in liver diseases. However, the pharmacological effect of Scoparone in non-alcoholic steatohepatitis (NASH) has not been elucidated. In this study, we investigated the protective effects and mechanisms of Scoparone in NASH. In vivo, the NASH model was established in mice fed a methionine and choline-deficient (MCD) diet for 4weeks, with or without simultaneous Scoparone treatment. In vitro, RAW264.7 cells induced by lipopolysaccharide (LPS) were pretreated with or without different concentrations of Scoparone. Hepatic triglycerides and serum AST and ALT levels were examined by biochemical assays. Hepatic histology was assessed by H&E, oil red O and Masson's trichrome staining methods, which were applied to analyze the protective effects of Scoparone in NASH. To further explore the underlying mechanism of Scoparone, immunohistochemistry, TUNEL, qRT-PCR, and Western blotting assays were applied to liver tissue or LPS-induced RAW264.7 cells. We found that Scoparone can effectively improve hepatic steatosis, apoptosis, inflammation, and fibrosis in an MCD diet-induced NASH murine model. Mechanistically, we demonstrated that Scoparone treatment alleviates NASH- and lipopolysaccharide (LPS)-induced immune responses in macrophages partly by blocking TLR-4/NF-κB signaling in a dose-dependent manner. Taken together, our results present the potential protective effects and mechanism of Scoparone in NASH, suggesting a potentially beneficial drug treatment for NASH.