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  ✔本篇論文使用華聯產品:Human OneArray  
 Phytomedicine. 2015, 22(7-8):768-77. doi: 10.1016/j.phymed.2015.05.053.
 Glycyrrhizin, silymarin, and ursodeoxycholic acid regulate a common hepatoprotective pathway in HepG2 cells 
 Chien-Yun Hsiang, Li-JenLin, Shung-Te Kao, Hsin-Yi Lo, Shun-Ting Chou, Tin-YunHo
  Abstract
BACKGROUND: Glycyrrhizin, silymarin, and ursodeoxycholic acid are widely used hepatoprotectants for the treatment of liver disorders, such as hepatitis C virus infection, primary biliary cirrhosis, and hepatocellular carcinoma. PURPOSE: The gene expression profiles of HepG2 cells responsive to glycyrrhizin, silymarin, and ursodeoxycholic acid were analyzed in this study. METHODS: HepG2 cells were treated with 25 µM hepatoprotectants for 24 h. Gene expression profiles of hepatoprotectants-treated cells were analyzed by oligonucleotide microarray in triplicates. Nuclear factor-£eB (NF-£eB) activities were assessed by luciferase assay. RESULTS: Among a total of 30,968 genes, 252 genes were commonly regulated by glycyrrhizin, silymarin, and ursodeoxycholic acid. These compounds affected the expression of genes relevant various biological pathways, such as neurotransmission, and glucose and lipid metabolism. Genes involved in hepatocarcinogenesis, apoptosis, and anti-oxidative pathways were differentially regulated by all compounds. Moreover, interaction networks showed that NF-£eB might play a central role in the regulation of gene expression. Further analysis revealed that these hepatoprotectants inhibited NF-£eB activities in a dose-dependent manner. CONCLUSION: Our data suggested that glycyrrhizin, silymarin, and ursodeoxycholic acid regulated the expression of genes relevant to apoptosis and oxidative stress in HepG2 cells. Moreover, the regulation by these hepatoprotectants might be relevant to the suppression of NF-£eB activities.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 Evidence-Based Complementary and Alternative Medicine. 2015:425760. doi: 10.1155/2015/425760.
 Molecular Signatures in the Prevention of Radiation Damage by the Synergistic Effect of N-Acetyl Cysteine and Qingre Liyan Decoction, a Traditional Chinese Medicine, Using a 3-Dimensional Cell Culture Model of Oral Mucositis
 
 
 Lavanya Kondapalli, Cyrus Parsa, Hari Chandana Mulamalla, Robert Orlando, Doreen Pon, Ying Huang, Moses S. S. Chow, Maria P. Lambros
  Abstract
Qingre Liyan decoction (QYD), a Traditional Chinese medicine, and N-acetyl cysteine (NAC) have been used to prevent radiation induced mucositis. This work evaluates the protective mechanisms of QYD, NAC, and their combination (NAC-QYD) at the cellular and transcriptional level. A validated organotypic model of oral mucosal consisting of a three-dimensional (3D) cell tissue-culture of primary human keratinocytes exposed to X-ray irradiation was used. Six hours after the irradiation, the tissues were evaluated by hematoxylin and eosin (H and E) and a TUNEL assay to assess histopathology and apoptosis, respectively. Total RNA was extracted and used for microarray gene expression profiling. The tissue-cultures treated with NAC-QYD preserved their integrity and showed no apoptosis. Microarray results revealed that the NAC-QYD caused the upregulation of genes encoding metallothioneins, HMOX1, and other components of the Nrf2 pathway, which protects against oxidative stress. DNA repair genes (XCP, GADD45G, RAD9, and XRCC1), protective genes (EGFR and PPARD), and genes of the NF£eB pathway were upregulated. Finally, tissue-cultures treated prophylactically with NAC-QYD showed significant downregulation of apoptosis, cytokines and chemokines genes, and constrained damage-associated molecular patterns (DAMPs). NAC-QYD treatment involves the protective effect of Nrf2, NF£eB, and DNA repair factors.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 Journal of Agricultural and Food Chemistry. 2014, 62(36):8952-61. doi: 10.1021/jf5002099.
 A Novel Insulin Receptor-Binding Protein from Momordica charantia Enhances Glucose Uptake and Glucose Clearance in Vitro and in Vivo through Triggering Insulin Receptor Signaling Pathway
 
 
 Chien-Yun Hsiang, Hsin-Yi Lo, Tin-Yun Ho, Chia-Cheng Li, Jaw-Chyun Chen, Jau-Jin Liu
  Abstract
Diabetes, a common metabolic disorder, is characterized by hyperglycemia. Insulin is the principal mediator of glucose homeostasis. In a previous study, we identified a trypsin inhibitor, named Momordica charantia insulin receptor (IR)-binding protein (mcIRBP) in this study, that might interact with IR. The physical and functional interactions between mcIRBP and IR were clearly analyzed in the present study. Photo-cross-linking coupled with mass spectrometry showed that three regions (17-21, 34-40, and 59-66 residues) located on mcIRBP physically interacted with leucine-rich repeat domain and cysteine-rich region of IR. IR-binding assay showed that the binding behavior of mcIRBP and insulin displayed a cooperative manner. After binding to IR, mcIRBP activated the kinase activity of IR by (5.87 ¡Ó 0.45)-fold, increased the amount of phospho-IR protein by (1.31 ¡Ó 0.03)-fold, affected phosphoinositide-3-kinase/Akt pathways, and consequently stimulated the uptake of glucose in 3T3-L1 cells by (1.36 ¡Ó 0.12)-fold. Intraperitoneal injection of 2.5 nmol/kg mcIRBP significantly decreased the blood glucose levels by 20.9 ¡Ó 3.2% and 10.8 ¡Ó 3.6% in normal and diabetic mice, respectively. Microarray analysis showed that mcIRBP affected genes involved in insulin signaling transduction pathway in mice. In conclusion, our findings suggest that mcIRBP is a novel IRBP that binds to sites different from the insulin-binding sites on IR and stimulates both theglucose uptake in cells and the glucose clearance in mice.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 PLoS One. 2014 Aug 18. doi: 10.1371/journal.pone.0104650.
 A Novel Glycated Hemoglobin A1c-Lowering Traditional Chinese Medicinal Formula, Identified by Translational Medicine Study
 
 
 Hsin-Yi Lo, Chien-Yun Hsiang, Tsai-Chung Li, Chia-Cheng Li, Hui-Chi Huang, Jaw-Chyun Chen, Tin-Yun Ho
  Abstract
Diabetes is a chronic metabolic disorder that has a significant impact on the health care system. The reduction of glycated hemoglobin A1c is highly associated with the improvements of glycemic control and diabetic complications. In this study, we identified a traditional Chinese medicinal formula with a HbA1c-lowering potential from clinical evidences. By surveying 9,973 diabetic patients enrolled in Taiwan Diabetic Care Management Program, we found that Chu-Yeh-Shih-Kao-Tang (CYSKT) significantly reduced HbA1c values in diabetic patients. CYSKT reduced the levels of HbA1c and fasting blood glucose, and stimulated the blood glucose clearance in type 2 diabetic mice. CYSKT affected the expressions of genes associated with insulin signaling pathway, increased the amount of phosphorylated insulin receptor in cells and tissues, and stimulated the translocation of glucose transporter 4. Moreover, CYSKT affected the expressions of genes related to diabetic complications, improved the levels of renal function indexes, and increased the survival rate of diabetic mice. In conclusion, this was a translational medicine study that applied a ¡§bedside-to-bench¡¨ approach to identify a novel HbA1c-lowering formula. Our findings suggested that oral administration of CYSKT affected insulin signaling pathway, decreased HbA1c and blood glucose levels, and consequently reduced mortality rate in type 2 diabetic mice.
   

  ✔本篇論文使用華聯產品:Rat OneArray  
 Journal of Ethnopharmacology. 2014 Jul 19. doi: 10.1016/j.jep.2014.07.022.
 Comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats and microarray analysis of drug-metabolizing genes
 
 
 Mei-Ling Hou, Li-WenChang, Chi-HungLin, Lie-ChwenLin, Tung-HuTsai
  Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Rhein is a pharmacological active component found in Rheum palmatum L. that is the major herb of the San-Huang-Xie-Xin-Tang (SHXXT), a medicinal herbal product used as a remedy for constipation. Here we have investigated the comparativepharmacokinetics of rhein in normal and constipated rats. Microarray analysis was used to explore whether drug-metabolizing genes will be altered after SHXXT treatment. MATERIALS AND METHODS: The comparative pharmacokinetics of rhein in normal and loperamide-induced constipated rats was studied by liquid chromatography with electrospray ionization tandem mass spectrometry (LC-MS/MS). Gene expression profiling in drug-metabolizing genes after SHXXT treatment was investigated by microarray analysis and real-time polymerase chain reaction (RT-PCR). Results: A validated LC-MS/MS method was applied to investigate the comparative pharmacokinetics of rhein in normal and loperamind-induced constipated rats. The pharmacokinetic results demonstrate that the loperamind-induced constipation reduced the absorption of rhein. Cmax significant reduced by 2.5-fold, the AUC decreased by 27.8%; however, the elimination half-life (t1/2) was prolonged by 1.6-fold. Tmax and mean residence time (MRT) were significantly prolonged by 2.8-fold, and 1.7-fold, respectively. The volume of distribution (Vss) increased by 2.2-fold. The data of microarray analysis on gene expression indicate that five drug-metabolizing genes, including Cyp7a1, Cyp2c6, Ces2e, Atp1b1, and Slc7a2 were significantly altered by the SHXXT (0.5 g/kg) treatment. Conclusion: The loperamide-induced constipation reduced the absorption of rhein. Since among the 25,338 genes analyzed, there were five genessignificantly altered by SHXXT treatment. Thus, information on minor drug-metabolizing genes altered by SHXXT treatment indicates that SHXXT is relatively safe for clinical application.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 Evidence-Based Complementary and Alternative Medicine. 2014 February 20.
 Deer Antler Extract Improves Fatigue Effect through Altering the Expression of Genes Related to Muscle Strength in Skeletal Muscle of Mice
 
 
 Jaw-Chyun Chen, Chien-Yun Hsiang, Yung-Chang Lin, Tin-Yun Ho
  Abstract
Deer antler is a well-known traditional Chinese medicine used in Asian countries for the tonic and the improvement of aging symptoms. The present study was designed to investigate the antifatigue effect and mechanism of Formosan sambar deer tip antler extract (FSDTAE). The swimming times to exhaustion of mice administered FSDTAE (8.2 mg/day) for 28 days were apparently longer than those of the vehicle-treated mice in forced swim test. However, the indicators of fatigue, such as the reduction in glucose level and the increases in blood urea nitrogen and lactic acid levels, were not significantly inhibited by FSDTAE. Therefore, microarray analysis was further used to examine the anti-fatigue mechanism of FSDTAE. We selected genes with fold changes >2 or <−2 in skeletal muscle for pathway analysis. FSDTAE-affected genes were involved in 9 different signaling pathways, such as GnRH signaling pathway and insulin signaling pathway. All of the significantly expressed genes were classified into 8 different categories by their functions. The most enriched category was muscular system, and 6 upregulated genes, such as troponin I, troponin T1, cysteine and glycine-rich protein 2, myosin heavy polypeptide 7, tropomyosin 2, and myomesin family member 3, were responsible for the development and contraction of muscle. Real-time PCR analysis indicated that FSDTAE increased troponins mRNA expression in skeletal muscle. In conclusion, our findings suggested that FSDTAE might increase the muscle strength through the upregulation of genes responsible for muscle contraction and consequently exhibited the anti-fatigue effect in mice.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 Journal of Ethnopharmacology. 2013, April 1. doi:10.1016/j.jep.2013.03.020.
 Screening and evaluation of traditional Chinese medicine by microarray expression analysis
 
 
 Guixiang Ren, Qionglin Liang, Yiming Wang, Xuemei Fan, Guoan Luo
  Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza is a Chinese medicinal herb, which is widely used for the treatment of cardiovascular disorders. In this article, we investigated the effects of Salvia miltiorrhiza and its hydrophilic and lipophilic components (HCS and LCS) on human umbilical vein endothelial cells (HUVECs), and the molecular mechanism was explored by microarray gene expression profiling. MATERIALS AND METHODS: Cell proliferation and migration were used to evaluate the angiogenic effects of HCS, LCS and total extract of Salvia miltiorrhiza (TES). Microarray technology was applied to detect the gene expression of HUVECs treated with TES, HCS and LCS. Besides, quantitative real-time PCR was used to verify the microarray results. RESULTS: Our results showed that LCS inhibited the proliferation and migration of HUVECs, HCS promoted the proliferation and migration of HUVECs, and TES did not affect the viability of HUVECs at the concentration of 5µg/mL. From the result of principle component analysis (PCA) of microarray data, the effect of LCS on HUVECs was significantly different from the other components. Moreover, there were more differentially expression genes in LCS group than in the other groups, which meant LCS had a strong influence on HUVECs. Compared with untreated cells, 511 significantly changed genes had been detected in LCS treated cells and 236 (approximately 46%) of them were up-regulated. The mRNA expression of IL-6 was found to be increased significantly in LCS group. CONCLUSIONS: In Salvia miltiorrhiza, HCS and LCS had opposite effects on HUVECs. LCS showed significantly inhibitory action on HUVECs proliferation and migration. It was proposed that LCS could apply in the diseases caused by vascular anomaly hyperplasia. In the mechanism of action of LCS on HUVECs, the pathways of ErbB, MAPK, p53, oxidative phosphorylation and inflammatory response were involved.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 Journal of Agricultural and Food Chemistry. 2013 Feb 15. doi: 10.1021/jf3042402.
 Momordica charantia and Its Novel Polypeptide Regulate the Glucose Homeostasis in Mice via Binding to Insulin Receptor
 
 
 Hsin-Yi Lo, Tin-Yun Ho, Chingju Lin, Chia-Cheng Li, Chien-Yun Hsiang
  Abstract
Momordica charantia (MC) has been used as an alternative therapy for diabetes mellitus. Herein we analyzed and elucidated therapeutic targets contributing to the hypoglycemic effect of aqueous extract of MC seeds (MCSE) by transcriptomic analysis. Protein ingredients aimed at the hypoglycemic target were further identified by proteomic, docking, and receptor-binding assays. Our data showed that MSCE (1 g/kg) significantly lowered the blood glucose level in normal and diabetic mice. Moreover, MCSE primarily regulated the insulin signaling pathway in muscles and adipose tissues, suggesting that MCSE might target to insulin receptor (IR), stimulate the IR-downstream pathway, and subsequently display the hypoglycemic activity in mice. We further identified that inhibitor against trypsin (TI) of MC directly docked into IR and activated the kinase activity of IR in a dose-dependent manner. In conclusion, our findings suggested that MCSE regulated glucose metabolism mainly via insulin signaling pathway. Moreover, we newly identified that TI was a novel IR-binding protein of MC that triggered the insulin signaling pathway via binding to IR.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 European journal of dermatology. 2012, 22(1): 58-67. doi: 10.1684/ejd.2011.1599.
 Angelica sinensis isolate SBD.4: composition, gene expression profiling, mechanism of action and effect on wounds, in rats and humans
 
 
 Hui Zhao, Joel Deneau, Ginny O.L. Che, Shang Li, Frederic Vagnini, Parastoo Azadi, Roberto Sonon, Ravi Ramjit, Simon M.Y. Lee, Krzysztof Bojanowski
  Abstract
This report characterizes an aqueous isolate (SBD.4) of one of the most broadly used Chinese medicinal herbs, Angelica sinensis, from the perspective of its application in skin and wound care. SBD.4 has been chemically defined and was found to increase the strength of healed wounds in retired breeder (older) rats. Furthermore, the mechanism of action of this Angelica sinensis isolate was tested in the zebrafish angiogenesis model, and in human skin substitutes by DNA microarray, revealing a bioactivity profile consistent with skin repair and regeneration. When combined with several types of wound dressings, SBD.4 increased type I collagen production in human dermal fibroblasts, and when formulated in nanosilver hydrocolloid dressing, it was found effective in chronic ulcer management in humans, demonstrating that botanical high-tech wound dressings can be successfully developed to improve the treatment of chronic lesions in humans.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 BioMedicine. 2012, 2(1):10-16. doi: 10.1016/j.biomed.2012.02.002.
 DNA microarray analysis as a tool to investigate the therapeutic mechanisms and drug development of Chinese medicinal herbs
 
 
 Chia-Cheng Li, Hsin-Yi Lo, Chien-Yun Hsiang, Tin-Yun Ho
  Abstract
Chinese herbal medicines have been used for the treatment of various diseases for centuries. Although several herbal formulas and herbal components have shown therapeutic potential, the active components and the molecular mechanisms mediating the effects of said formulas remain to be discovered. Microarray analysis has become a widely used tool for the generation of gene expression data on a genome-wide scale. This paper discusses the application of whole genome expression profiling as a tool to investigate the molecular mechanisms governing the therapeutic effects of traditional Chinese medicine. This review also highlights how data derived from DNA microarray analysis can be used to screen for drug targets of various herbal drugs, to predict the therapeutic potential of herbal drugs, to analyze the safety of drugs in the preclinical stage of drug development, and to establish a modern definition of traditional Chinese medicine.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 Food Chemistry. 2013, 136(2):426-34. doi: 10.1016/j.foodchem.2012.08.009.
 Toona sinensis and its major bioactive compound gallic acid inhibit LPS-induced inflammation in nuclear factor-£eB transgenic mice as evaluated by in vivo bioluminescence imaging
 
 
 Chien-Yun Hsiang, You-Cheng Hseu, Yi-Chih Chang, K.J. Senthil Kumar, Tin-Yun Ho, Hsin-Ling Yang
  Abstract
In the present study, we investigated the anti-inflammatory effects of a nutritious vegetable Toona sinensis (leaf extracts, TS) and its major bioactive compound gallic acid (GA) by analysing LPS-induced NF-£eB activation in transgenic mice, using bioluminescence imaging. Mice were challenged intraperitoneally with LPS (1 mg/kg) and treated orally with TS or GA (100 or 5 mg/kg, respectively). In vivo and ex vivo imaging showed that LPS increased NF-£eB luminescence in the abdominal region, which was significantly inhibited by TS or GA. Immunohistochemical and ELISA analyses confirmed that TS and GA inhibited LPS-induced NF-£eB, interleukin-1£], and tumour necrosis factor-£ expression. Microarray analysis revealed that biological pathways associated with metabolism and the immune responses were affected by TS or GA. Particularly, LPS-induced thioredoxin-like 4B (TXNL4B) 2 expression in the small intestine, and TXNL4B, iNOS, and COX-2 expression in RAW 264.7 cells were significantly inhibited by TS or GA. Thus, the anti-inflammatory potential of TS was mediated by the downregulation of NF-£eB pathway.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 Food Chemistry. 2013, 136(1):170-7. doi: 10.1016/j.foodchem.2012.07.124.
 Ginger extract and zingerone ameliorated trinitrobenzene sulfonic acid-induced colitis in mice via modulation of nuclear factor-£eB activity and interleukin-1£] signaling pathway
 
 
 Chien-Yun Hsiang, Hsin-Yi Lo, Hui-Chi Huang, Chia-Cheng Li, Shih-Lu Wu, Tin-Yun Ho
  Abstract
Ginger is a commonly used spice with anti-inflammatory potential. Colitis is the common pathological lesion of inflammatory bowel diseases. In this study, we investigated the therapeutic effects of ginger and its component zingerone in mice with 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis. Ginger and zingerone ameliorated TNBS-induced colonic injury in a dose-dependent manner. Pathway analysis of ginger- and zingerone-regulated gene expression profiles showed that ginger and zingerone significantly regulated cytokine-related pathways. Network analysis showed that nuclear factor-£eB (NF-£eB) and interleukin-1£] (IL-1£]) were key molecules involved in the expression of ginger- and zingerone-affected genes. Ex vivo imaging and immunohistochemical staining further verified that ginger and zingerone suppressed TNBS-induced NF-£eB activation and IL-1£] protein level in the colon. In conclusion, ginger improved TNBS-induced colitis via modulation of NF-£eB activity and IL-1£] signalling pathway. Moreover, zingerone might be the active component of ginger responsible for the amelioration of colitis induced by TNBS.
   

  ✔本篇論文使用華聯產品:Human miRNA OneArray  
 PLoS ONE. 2012, 7(1):e30635. doi: 10.1371/journal.pone.0030635 .
 microRNA-152 Mediates DNMT1-Regulated DNA Methylation in the Estrogen Receptor £ Gene
 
 
 Yung-Song Wang, Wen-Wen Chou, Ku-Chung Chen, Hsin-Yun Cheng, Ruey-Tay Lin, Suh-Hang Hank Juo
  Abstract
"Estrogen receptor a (ERa) has been shown to protect against atherosclerosis. Methylation of the ERa gene can reduce ERa expression leading to a higher risk for cardiovascular disease. Recently, microRNAs have been found to regulate DNA methyltransferases (DNMTs) and thus control methylation status in several genes. We first searched for microRNAs involved in DNMT-associated DNA methylation in the ERa gene. We also tested whether statin and a traditional Chinese medicine (San-Huang-Xie-Xin-Tang, SHXXT) could exert a therapeutic effect on microRNA, DNMT and ERa methylation. The ERa expression was decreased and ERa methylation was increased in LPS-treated human aortic smooth muscle cells (HASMCs) and the aorta from rats under a high-fat diet. microRNA-152 was found to be down regulated in the LPS-treated HASMCs. We validated that microRNA-152 can knock down DNMT1 in HASMCs leading to hypermethylation of the ERa gene. Statin had no effect on microRNA-152, DNMT1 or ERa expression. On the contrary, SHXXT could restore microRNA-152, decrease DNMT1 and increase ERa expression in both cellular and animal studies. The present study showed that microRNA-152 decreases under the pro-atherosclerotic conditions. The reduced microRNA-152 can lose an inhibitory effect on DNA methyltransferase, which leads to hypermethylation of the ERa gene and a decrease of ERa level. Although statin can not reverse these cascade proatherosclerotic changes, the SHXXT shows a promising effect to inhibit this unwanted signaling pathway."
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 Biotechnol Lett. 2012, 34(5):805-12. doi: 10.1007/s10529-011-0838-7.
 Momilactione B inhibits protein kinase A signaling and reduces tyrosinase-related proteins 1 and 2 expression in melanocytes
 
 
 Ji Hae Lee, Boram Cho, Hee-jin Jun, Woo-Duck Seo, Dong-Woo Kim, Kang-Jin Cho, Sung-Joon Lee
  Abstract
Momilactone B (MB) is a terpenoid phytoalexin present in rice bran that exhibits several biological activities. MB reduced the melanin content in B16 melanocytes melanin content and inhibited tyrosinase activities. Using transcriptome analysis, the genes involved in protein kinase A (PKA) signaling were found to be markedly altered. B16 cells stimulated with MB had decreased concentrations of cAMP protein kinase A activity, and cAMP-response element-binding protein which is a key transcription factor for microphthalmia-associated transcription factor (MITF) expression. Accordingly, the expression of MITF and its target genes, which are essential for melanogenesis, were reduced. MB thus exhibits anti-melanogenic effects by repressing tyrosinase enzyme activity and inhibiting the PKA signaling pathway which, in turn, decreases melanogenic gene expression.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 Eur J Dermatol. 2012, 22(1):58-67. doi: 10.1684/ejd.2011.1599.
 Angelica sinensis isolate SBD.4: composition, gene expression profiling, mechanism of action and effect on wounds, in rats and humans
 
 
 Hui ZHAO, Joel DENEAU, Ginny O.L. CHE, Shang LI, Frederic VAGNINI, Parastoo AZADI, Roberto SONON, Ravi RAMJIT, Simon M.Y. LEE, Krzysztof BOJANOWSKI
  Abstract
This report characterizes an aqueous isolate (SBD.4) of one of the most broadly used Chinese medicinal herbs, Angelica sinensis, from the perspective of its application in skin and wound care. SBD.4 has been chemically defined and was found to increase the strength of healed wounds in retired breeder (older) rats. Furthermore, the mechanism of action of this Angelica sinensis isolate was tested in the zebrafish angiogenesis model, and in human skin substitutes by DNA microarray, revealing a bioactivity profile consistent with skin repair and regeneration. When combined with several types of wound dressings, SBD.4 increased type I collagen production in human dermal fibroblasts, and when formulated in nanosilver hydrocolloid dressing, it was found effective in chronic ulcer management in humans, demonstrating that botanical high-tech wound dressings can be successfully developed to improve the treatment of chronic lesions in humans.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 Acta Pharmacol Sin. 2010, 31(2):227-36. doi: 10.1038/aps.2009.197.
 Microarray analysis reveals the inhibition of nuclear factor-kappa B signaling by aristolochic acid in normal human kidney (HK-2) cells
 
 
 Chen YY, Chiang SY, Wu HC, Kao ST, Hsiang CY, Ho TY, Lin JG.
  Abstract
To study the molecular mechanism underlying the effect of aristolochic acid (AA), a major active component of plants from the Aristolochiaceae family using microarray analysis. Human kidney (HK-2) cells were treated with AA (0, 10, 30, and 90 micromol/L) for 24 h, and the cell viability was measured by a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide assay. Complementary DNA microarrays were used to investigate the gene expression pattern of HK-2 cells exposed to AA in triplicate. A quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assay was used to verify the microarray data for selected nuclear factor kappa B (NF-kappaB)-regulated genes. Furthermore, the subcellular localization of NF-kappaB p65 was visualized by immunofluorescence confocal microscopy in HK-2 cells. The NF-kappaB activity was examined by a luciferase reporter assay in HK-2/NF-kappaB transgenic cells. AA exhibited a dose-dependent cytotoxic effect in HK-2 cells and induced alterations in the gene expression profiles related to the DNA damage response, DNA repair, macromolecule metabolic process, carbohydrate metabolic process, DNA metabolic process, apoptosis, cell cycle, and transcription. In addition, 9 biological pathways associated with immunomodulatory functions were down-regulated in AA-treated HK-2 cells. A network analysis revealed that NF-kappaB played a central role in the network topology. Among NF-kappaB-regulated genes, 8 differentially expressed genes were verified by qRT-PCR. The inhibition of NF-kappaB activity by AA was further confirmed by immunofluorescence confocal microscopy and by NF-kappaB luciferase reporter assay. Our data revealed that AA could suppress NF-kappaB activity in normal human cells, perhaps partially accounting for the reported anti-inflammatory effects of some plants from the genus Aristolochia.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 Journal of Environmental Science and Health. 2010, 28(1):60-87. doi: 10.1080/10590500903585416.
 Gene Expression Profiling as an Initial Approach for Mechanistic Studies of Toxicity and Tumorigenicity of Herbal Plants and Herbal Dietary Supplements.
 
 
 Nan Mei, Qingsu Xia, Tao Chen, Po-Chuen Chan, Peter P. Fu, Lei Guo
  Abstract
Dietary supplements are consumed by more than 300 million people worldwide, and herbal dietary supplements represent the most rapidly growing portion of this industry. Even though adverse health effects of many herbal dietary supplements have been reported, safety assurances are not being addressed adequately. Toxicological data on the identification of genotoxic and tumorigenic ingredients in many raw herbs are also lacking. Currently, more than 30 herbal dietary supplements and active ingredients have been selected by the National Toxicology Program (NTP) for toxicity and tumorigenicity studies. Due to the complexity of the chemical components present in plant extracts, there are no established methodologies for determining the mechanisms of toxicity (particularly tumorigenicity) induced by herbs, such as Gingko biloba leaf extract (GBE) and other herbal plant extracts. Consequently, the understanding of toxicity of herbal dietary supplements remains limited. We have proposed that application of DNA microarrays could be a highly practical initial approach for revealing biological pathways and networks associated with toxicity induced by herbal dietary supplements and the generation of hypotheses to address likely mechanisms. The changes in expression of subsets of genes of interest, such as the modulation of drug metabolizing genes, can be analyzed after treatment with an herbal dietary supplement. Although levels of gene expression do not represent fully the levels of protein activities, we propose that subsequent biochemical and genomic experiments based on these initial observations will enable elucidation of the mechanisms leading to toxicity, including tumorigenicity. This review summarizes the current practices of microarray analysis of gene expressions in animals treated with herbal dietary supplements and discusses perspectives for the proposed strategy.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 Journal of Ethnopharmacology. 2010, 132(2):429-37. doi: 10.1016/j.jep.2010.08.022.
 Application of bioactivity database of Chinese herbal medicine on the therapeutic prediction, drug development, and safety evaluation.
 
 
 Cheng HM, Li CC, Chen CY, Lo HY, Cheng WY, Lee CH, Yang SZ, Wu SL, Hsiang CY, Ho TY.
  Abstract
Chinese herbal medicine has been used for the treatments of various diseases for years. However, it is often difficult to analyze their biological activities and molecule mechanisms because of their complex nature. In this study, we applied DNA microarray to analyze the biological events induced by herbal formulae, predict the therapeutic potentials of formulae, and evaluate the safety of formulae. Mice were administrated orally with 15 formulae for 7 consecutive days, and the gene expression profiles in liver or kidney were further analyzed by transcriptomic tools. Our data showed that most formulae altered the metabolic pathways, such as glutathione metabolism and oxidative phosphorylation, and regulatory pathways, such as antigen processing and presentation and insulin-like growth factor signaling pathway. By comparing the gene expression signatures of formulae with those of disease states or drugs, we found that mice responsive to formula treatments might be related to disease states, especially metabolic and cardiovascular diseases, and drugs, which exhibit anti-cancer, anti-inflammatory, and anti-oxidative effects. Moreover, most formulae altered the expression levels of cytochrome p450, glutathione S-transferase, and UDP glycosyltransferase genes, suggesting that caution should be paid to possible drug interaction of these formulae. Furthermore, the similarities of gene expression profiles between formulae and toxic chemicals were low in kidney, suggesting that these formulae might not induce nephrotoxicities in mice. This report applied transcriptomic tools as a novel platform of translational medicine for Chinese herbal medicine. This platform will not only for understanding the therapeutic mechanisms involving herbal formulae and gene interactions, but also for the new theories in drug discovery.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 Vaccine. 2010, 28(31):4945-54.
 Immunomodulatory and adjuvant activities of a polysaccharide extract of Ganoderma lucidum in vivo and in vitro.
 
 
 Lai CY, Hung JT, Lin HH, Yu AL, Chen SH, Tsai YC, Shao LE, Yang WB, Yu J.
  Abstract
We had isolated a high molecular weight polysaccharide fraction, designated as F3, and performed a comprehensive analysis of its immunomodulatory and adjuvant activities in vivo and in vitro. In vivo, F3-treated mice showed an increase in the number of dendritic cells as well as CD4, CD8, regulatory T, B, plasma, NK, and NKT cells in the spleen. F3 also elevated the levels of multiple cytokines and chemokines in the blood of mice. F3 displayed potent adjuvant activity for tetanus toxoid in the absence of alum and potentiated antibody responses to alum-containing tetanus toxoid in mice. In addition, F3 also boosted Th1 and Th2 response in vivo. In vitro, F3 induced the maturation of dendritic cells derived from human monocytes by upregulating CD40, CD54, CD80, CD83, CD86, and HLA-DR, enhanced mixed lymphocyte reaction, and stimulated the production of ten cytokines and six chemokines. In microarray analysis, expressions of 7688 genes were modulated in dendritic cells after treatment with F3, including cytokine and chemokine genes. These results provide F3 polysaccharide extract further insight into the mechanisms of action for these immunomodulatory and adjuvant activities of from Ganoderma lucidum and also offer preclinical evidence for its development as a vaccine adjuvant.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 OMICS: A Journal of Integrative Biology. 2010, 14(1):75-90. doi: 10.1089/omi.2009.0115.
 Ginkgo Biloba Extract Induces Gene Expression Changes in Xenobiotics Metabolism and the Myc-Centered Network.
 
 
 Nan Mei, Wayne Liao, Po-Chuen Chan, Peter P. Fu, Lei Guo
  Abstract
The use of herbal dietary supplements in the United States is rapidly growing, and it is crucial that the quality and safety of these preparations be ensured. To date, it is still a challenge to determine the mechanisms of toxicity induced by mixtures containing many chemical components, such as herbal dietary supplements. We previously proposed that analyses of the gene expression profiles using microarrays in the livers of rodents treated with herbal dietary supplements is a potentially practical approach for understanding the mechanism of toxicity. In this study, we utilized microarrays to analyze gene expression changes in the livers of male B6C3F1 mice administered Ginkgo biloba leaf extract (GBE) by gavage for 2 years, and to determine pathways and mechanisms associated with GBE treatments. Analysis of 31,802 genes revealed that there were 129, 289, and 2,011 genes significantly changed in the 200, 600, and 2,000 mg/kg treatment groups, respectively, when compared with control animals. Drug metabolizing genes were significantly altered in response to GBE treatments. Pathway and network analyses were applied to investigate the gene relationships, functional clustering, and mechanisms involved in GBE exposure. These analyses indicate alteration in the expression of genes coding for drug metabolizing enzymes, the NRF2-mediated oxidative stress response pathway, and the Myc gene-centered network named "cell cycle, cellular movement, and cancer" were found. These results indicate that Ginkgo biloba-related drug metabolizing enzymes may cause herb-drug interactions and contribute to hepatotoxicity. In addition, the outcomes of pathway and network analysis may be used to elucidate the toxic mechanisms of Ginkgo biloba.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 FOOD CHEM TOXICOL. 2010, 48(2):686-96. doi: 10.1016/j.fct.2009.11.050.
 Gene expression profiling in male B6C3F1 mouse livers exposed to kava identifies ¡V Changes in drug metabolizing genes and potential mechanisms linked to kava toxicity.
 
 
 Qiang Shi, Stacey Dial, Qingsu Xia, Nan Mei, Quan-Zhen Li, Po-Chuen Chan, Peter P. Fu, Lei Guo
  Abstract
The association of kava products with liver-related health risks has prompted regulatory action in many countries. We used a genome-wide gene expression approach to generate global gene expression profiles from the livers of male B6C3F1 mice administered kava extract by gavage for 14 weeks, and identified the differentially expressed drug metabolizing genes in response to kava treatments. Analyses of gene functions and pathways reveal that the levels of significant numbers of genes involving drug metabolism were changed and that the pathways involving xenobiotics metabolism, Nrf2-mediated oxidative stress response, mitochondrial functions and others, were altered. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, potentially leading to herb-drug interactions and hepatotoxicity.
   

  ✔本篇論文使用華聯產品:Mouse OneArray  
 Journal of Ethnopharmacology. 2009, 123(1):68-73. doi: 10.1016/j.jep.2009.02.027.
 Transcriptomic analysis of EGb 761-regulated neuroactive receptor pathway in vivo.
 
 
 Su SY, Hsieh CL, Wu SL, Cheng WY, Li CC, Lo HY, Ho TY, Hsiang CY.
  Abstract
Although EGb 761 exhibits neuroprotective effects and exerts beneficial effects on many neurological disorders, its mechanism on the neuronal functions is unclear so far. In this study, we used oligonucleotide microarray technique to investigate the effect of EGb 761 on the transcriptional profile of mouse genes. RNA samples were obtained from frontal cortex, straitum, and kidneys after the oral administration of EGb 761 for seven consecutive days. Our data showed that EGb 761 significantly altered the neuroactive ligand-receptor interaction pathway in frontal cortex but not in straitum and kidney. Then we analyzed 26 receptor genes that were significantly altered by EGb 761 in this pathway and found that EGb 761 treatment highly up-regulated the subgroup of dopamine receptors, especially dopamine receptor 1a (Drd1a), in frontal cortex. Quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemical staining confirmed the increased level of Drd1a expression after EGb 761 treatment. In summary, we investigated for the first time the overall effects of EGb 761 on the gene expression in brain using a powerful systemic biological technique. Our results suggested that EGb 761 altered unique pathways and regulated the expressions of some specific neuronal receptor genes exclusively in frontal cortex.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 MOLECULAR PHARMACOLOGY. 2009, 75(1):151-7. doi: 10.1124/mol.108.049502.
 Vanillin Inhibits Matrix Metalloproteinase-9 Expression through Down-Regulation of Nuclear Factor- B Signaling Pathway in Human Hepatocellular Carcinoma Cells.
 
 
 Liang JA, Wu SL, Lo HY, Hsiang CY, Ho TY
  Abstract
Vanillin has been reported to exhibit anti-invasive and antimetastatic activities by suppressing the enzymatic activity of matrix metalloproteinase-9 (MMP-9). However, the underlying mechanism of anti-invasive activity remains unclear so far. Herein we demonstrate that vanillin reduced 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 gelatinolytic activity and suppressed cell invasion through the down-regulation of MMP-9 gene transcription in HepG2 cells. Vanillin significantly reduced the 6.6-fold invasive capacity of HepG2 cells in noncytotoxic concentrations, and this anti-invasive effect was concentration-dependent in the Matrigel invasion assay. Moreover, vanillin significantly suppressed the TPA-induced enzymatic activity of MMP-9 and decreased the induced mRNA level of MMP-9. Analysis of the transcriptional regulation indicated that vanillin suppressed MMP-9 transcription by inhibiting nuclear factor-kappaB (NF-kappaB) activity. Western blot further confirmed that vanillin inhibited NF-kappaB activity through the inhibition of IkappaB-alpha phosphorylation and degradation. In conclusion, vanillin might be a potent antiinvasive agent that suppresses the MMP-9 enzymatic activity via NF-kappaB signaling pathway.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 The American Journal of Chinese Medicine. 2008, 36(4):783-97. doi: 10.1142/S0192415X08006235.
 Relationship Between San-Huang-Xie-Xin-Tang and Its Herbal Components on the Gene Expression Profiles in HepG2 Cells.
 
 
 Cheng WY, Wu SL, Hsiang CY, Li CC, Lai TY, Lo HY, Shen WS, Lee CH, Chen JC, Wu HC, Tin-Yun Ho
  Abstract
Traditional Chinese medicine (TCM) has been used for thousands of years. Most Chinese herbal formulae consist of several herbal components and have been used to treat various diseases. However, the mechanisms of most formulae and the relationship between formulae and their components remain to be elucidated. Here we analyzed the putative mechanism of San-Huang-Xie-Xin-Tang (SHXXT) and defined the relationship between SHXXT and its herbal components by microarray technique. HepG2 cells were treated with SHXXT or its components and the gene expression profiles were analyzed by DNA microarray. Gene set enrichment analysis indicated that SHXXT and its components displayed a unique anti-proliferation pattern via p53 signaling, p53 activated, and DNA damage signaling pathways in HepG2 cells. Network analysis showed that most genes were regulated by one molecule, p53. In addition, hierarchical clustering analysis showed that Rhizoma Coptis shared a similar gene expression profile with SHXXT. These findings may explain why Rhizoma Coptis is the principle herb that exerts the major effect in the herbal formula, SHXXT. Moreover, this is the first report to reveal the relationship between formulae and their herbal components in TCM by microarray and bioinformatics tools.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 Cancer Biology & Therapy. 2008, 7(4):577-86. doi: 10.1371/journal.pone.0030107.
 Molecular mechanisms underlying selective cytotoxic activity of BZL101, an extract of Scutellaria barbata, towards breast cancer cells.
 
 
 Fong S, Shoemaker M, Cadaoas J, Lo A, Liao W, Tagliaferri M, Cohen I, Emma Shtivelman
  Abstract
We studied the mechanism of the cytotoxic activity of BZL101, an aqueous extract from the herb Scutellaria barbata D. Don, which is currently in phase II clinical trial in patients with advanced breast cancer. The phase I trial showed favorable toxicity profile and promising efficacy. We report here that BZL101 induces cell death in breast cancer cells but not in non-transformed mammary epithelial cells. This selective cytotoxicity is based on strong induction by BZL101 of reactive oxygen species (ROS) in tumor cells. As a consequence, BZL101 treated cancer cells develop extensive oxidative DNA damage and succumb to necrotic death. Data from the expression profiling of cells treated with BZL101 are strongly supportive of a death pathway that involves oxidative stress, DNA damage and activation of death-promoting genes. In breast cancer cells oxidative damage induced by BZL101 leads to the hyperactivation of poly (ADP-ribose) polymerase (PARP), followed by a sustained decrease in levels of NAD and depletion of ATP, neither of which are observed in non-transformed cells. The hyperactivation of PARP is instrumental in the necrotic death program induced by BZL101, because inhibition of PARP results in suppression of necrosis and activation of the apoptotic death program. BZL101 treatment leads to the inhibition of glycolysis selectively in tumor cells, evident from the decrease in the enzymatic activities within the glycolytic pathway and the inhibition of lactate production. Because tumor cells frequently rely on glycolysis for energy production, the observed inhibition of glycolysis is likely a key factor in the energetic collapse and necrotic death that occurs selectively in breast cancer cells. The promising selectivity of BZL101 towards cancer cells is based on metabolic differences between highly glycolytic tumor cells and normal cells.
   

  ✔本篇論文使用華聯產品:Human OneArray  
 Pharmacological research. 2007, 56(6):474-82. doi:10.1016/j.phrs.2007.09.009.
 Microarray analysis of vanillin-regulated gene expression profile in human hepatocarcinoma cells.
 
 
 Cheng WY, Hsiang CY, Bau DT, Chen JC, Shen WS, Li CC, Lo HY, Wu SL, Chiang SY, Tin-Yun Ho
  Abstract
Vanillin is one of the most widely used flavor compounds in food and personal products. It has been reported that vanillin is able to inhibit mutagenesis induced by chemical and physical mutagens, and to suppress the invasion and migration of cancer cells. Herein we used the oligonucleotide microarray approach to study gene expression profile of vanillin-treated human hepatocarcinoma cells. Microarray data followed by gene ontology (GO) investigation displayed that vanillin-affected clusters of genes involved in cell cycle and apoptosis. Genes down-regulated by vanillin were grouped into three GO categories, regulation of cellular process, cell cycle, and death. Furthermore, most of the down-regulated genes were associated with cancer progression. Knowledge-based analysis further indicated that Fos may play a central role in the regulation of gene expression network. Analysis of Fos-related transcription factor, activator protein 1 (AP-1), showed that vanillin inhibited AP-1 activity in a dose-dependent manner. Furthermore, the phosphorylation of extracellular signal-regulated protein kinase (ERK) was diminished with increasing concentrations of vanillin, indicating that vanillin-regulated AP-1 activity via ERK pathway. In conclusion, our data suggested that vanillin exhibited the anticancer potential by the regulations of cell cycle and apoptosis. Moreover, its regulation may involve the suppression of a central molecule, AP-1.