scholarly journals Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics

2021 ◽  
Vol 14 (10) ◽  
pp. 1010
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Heart Diseases ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Ginseng Root ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Positive Effects ◽  
Wide Range

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, or loss of concentration, and during recovery. According to ancient records, red ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their levels in blood is low—at concentrations from 10−6 to 10−18 M. In the present study, we compared the effects of red ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/mL with effects of white ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression in isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up- or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially varied effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10,000 to 0.01 ng/mL. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.

scholarly journals Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics

2021 ◽  
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Heart Diseases ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Ginseng Root ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Positive Effects ◽  
Wide Range

Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, loss of concentration, and during recovery. According to ancient records, Red Ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their level in blood is shallow - at concentrations from 10-6 to 10-18 M. In the present study, we compared the effects of Red Ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/ml with effects of White Ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression of isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up-or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially various effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10000 to 0.01 ng/ml. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.

scholarly journals Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations

2021 ◽  
Vol 14 (10) ◽  
pp. 999
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Toxic Concentration ◽  
Wide Range ◽  
Ginsenoside Rg5

Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than those detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major “rare” ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10−4 to 10−18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10−6 M to 10−18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10−4 M. Network pharmacology analyses of genes’ expression profiles using ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

scholarly journals Network Pharmacology of Red Ginseng (Part I): Effects of Ginsenoside Rg5 at Physiological and Sub-Physiological Concentrations

2021 ◽  
Author(s):  
Alexander Panossian ◽  
Sara Abdelfatah ◽  
Thomas Efferth
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Network Pharmacology ◽  
Pharmacokinetic Studies ◽  
Red Ginseng ◽  
Toxic Concentration ◽  
Wide Range ◽  
Ginsenoside Rg5

Numerous in vitro studies on isolated cells have been conducted to uncover the molecular mechanisms of action of Panax ginseng Meyer root extracts and purified ginsenosides. However, the concentrations of ginsenosides and the extracts used in these studies were much higher than detected in pharmacokinetic studies in humans and animals orally administered with ginseng preparations at therapeutic doses. Our study aimed to assess: (a) the effects of ginsenoside Rg5, the major "rare" ginsenoside of Red Ginseng, on gene expression in the murine neuronal cell line HT22 in a wide range of concentrations, from 10-4 to 10-18 M, and (b) the effects of differentially expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in HT22 cells after treatment with ginsenoside Rg5. Ginsenoside Rg5 exhibits soft-acting effects on gene expression of neuronal cells in a wide range of physiological concentrations and strong reversal impact at high (toxic) concentration: significant up- or downregulation of expression of about 300 genes at concentrations from 10-6 M to 10-18 M, and dramatically increased both the number of differentially expressed target genes (up to 1670) and the extent of their expression (fold changes compared to unexposed cells) at a toxic concentration of 10-4 M. Network pharmacology analyses of genes expression profiles using Ingenuity pathway analysis (IPA) software showed that at low physiological concentrations, ginsenoside Rg5 has the potential to activate the biosynthesis of cholesterol and to exhibit predictable effects in senescence, neuroinflammation, apoptosis, and immune response, suggesting soft-acting, beneficial effects on organismal death, movement disorders, and cancer.

scholarly journals Characterization of Metabolites and Transcripts Involved in Flower Pigmentation in Primula vulgaris

2020 ◽  
Vol 11 ◽  
Author(s):  
Long Li ◽  
Jing Ye ◽  
Houhua Li ◽  
Qianqian Shi
Keyword(s):  
Gene Expression ◽  
Metabolic Networks ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Flower Color ◽  
Myb Transcription Factor ◽  
High Accumulation ◽  
Primula Vulgaris ◽  
Wide Range

Primula vulgaris exhibits a wide range of flower colors and is a valuable ornamental plant. The combination of flavonols/anthocyanins and carotenoids provides various colorations ranging from yellow to violet-blue. However, the complex metabolic networks and molecular mechanisms underlying the different flower colors of P. vulgaris remain unclear. Based on comprehensive analysis of morphological anatomy, metabolites, and gene expression in different-colored flowers of P. vulgaris, the mechanisms relating color-determining compounds to gene expression profiles were revealed. In the case of P. vulgaris flower color, hirsutin, rosinin, petunidin-, and cyanidin-type anthocyanins and the copigment herbacetin contributed to the blue coloration, whereas peonidin-, cyandin-, and delphinidin-type anthocyanins showed high accumulation levels in pink flowers. The color formation of blue and pink were mainly via the regulation of F3′5′H (c53168), AOMT (c47583, c44905), and 3GT (c50034). Yellow coloration was mainly due to gossypetin and carotenoid, which were regulated by F3H (c43100), F3 1 (c53714), 3GT (c53907) as well as many carotenoid biosynthetic pathway-related genes. Co-expression network and transient expression analysis suggested a potential direct link between flavonoid and carotenoid biosynthetic pathways through MYB transcription factor regulation. This work reveals that transcription changes influence physiological characteristics, and biochemistry characteristics, and subsequently results in flower coloration in P. vulgaris.

scholarly journals AMPKβ1 and AMPKβ2 define an isoform-specific gene signature in human pluripotent stem cells, differentially mediating cardiac lineage specification

2020 ◽  
Vol 295 (51) ◽  
pp. 17659-17671
Author(s):  
Nicole Ziegler ◽  
Erik Bader ◽  
Alexey Epanchintsev ◽  
Daniel Margerie ◽  
Aimo Kannt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Specific Gene ◽  
Wide Range ◽  
Specific Manner ◽  
Cardiac Lineage

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression.

scholarly journals Predicting compound activity from phenotypic profiles and chemical structures

2020 ◽  
Author(s):  
Tim Becker ◽  
Kevin Yang ◽  
Juan C Caicedo ◽  
Bridget K Wagner ◽  
Vlado C Dancik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Deep Learning ◽  
Drug Discovery ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Relative Strength ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
Chemical Structures ◽  
Wide Range

Recent advances in deep learning enable using chemical structures and phenotypic profiles to accurately predict assay results for compounds virtually, reducing the time and cost of screens in the drug discovery process. The relative strength of high-throughput data sources - chemical structures, images (Cell Painting), and gene expression profiles (L1000) - has been unknown. Here we compare their ability to predict the activity of compounds structurally different from those used in training, using a sparse dataset of 16,979 chemicals tested in 376 assays for a total of 542,648 readouts. Deep learning-based feature extraction from chemical structures provided a remarkable ability to predict assay activity for structures dissimilar to those used for training. Image-based profiling performed even better, but requires wet lab experimentation. It outperformed gene expression profiling, and at lower cost. Furthermore, the three profiling modalities are complementary, and together can predict a wide range of diverse bioactivity, including cell-based and biochemical assays. Our study shows that, for many assays, predicting compound activity from phenotypic profiles and chemical structures is an accurate and efficient way to identify potential treatments in the early stages of the drug discovery process.

scholarly journals Quercetin supplementation and its effect on human monocyte gene expression profiles in vivo

2010 ◽  
Vol 104 (3) ◽  
pp. 336-345 ◽  
Author(s):  
Inka Boomgaarden ◽  
Sarah Egert ◽  
Gerald Rimbach ◽  
Siegfried Wolffram ◽  
Manfred J. Müller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Human Monocyte ◽  
Controlled Study ◽  
Nucleic Acid Metabolism ◽  
Double Blind ◽  
Wide Range

Quercetin has been described as having a wide range of beneficial effects in humans, ranging from anti-carcinogenic properties to reducing the risk of CVD. Nevertheless, underlying molecular mechanisms have been mostly investigated in vitro. Here, we tested whether a daily supplementation of quercetin leads to reproducible changes in human monocyte gene expression profiles. In study I, quercetin in varying dosages was given to healthy subjects for 2 weeks. RNA from monocytes isolated at the beginning and end of the study from subjects receiving 150 mg quercetin per d was subjected to transcriptome-wide microarray analysis. In study II, a double-blind cross-over study, twenty subjects exhibiting a ‘cardiovascular risk phenotype’ received 150 mg quercetin or placebo daily for 6 weeks each and served as the verification group. Microarray analysis revealed a number of differentially expressed genes. The most significantly represented functional groups were those of the immune system, nucleic acid metabolism, apoptosis and O-glycan biosynthesis. Twenty-four genes were chosen for technical replication and independent verification by quantitative real-time PCR. When comparing placebo and quercetin treatment, four genes showed significantly different expression changes (C1GALT1, O-glycan biosynthesis; GM2A, glycolipid catabolism; HDGF, cell proliferation; SERPINB9, apoptosis). However, these were minimal in respect to magnitude of fold change. In conclusion, although microarray analysis revealed extensive effects of quercetin on gene expression, the employment of a placebo-controlled study design showed no comparable results for twenty-four verification targets. This emphasises the need for stringent designs in nutritional intervention studies with the aim to identify relevant changes in gene expression.

scholarly journals Managing Gene Expression in Pseudomonas Simiae EGD-AQ6 for Chloroaromatic Compound Degradation

2021 ◽  
Author(s):  
Saheli Ghosh ◽  
Hemant Purohit ◽  
Asifa Qureshi
Keyword(s):  
Gene Expression ◽  
Sequence Similarity ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Dichlorophenoxyacetic Acid ◽  
Potential Candidate ◽  
Positive Effects ◽  
Catabolic Genes ◽  
Aromatic Degradation ◽  
Intermediate Metabolite

Abstract Pseudomonas simiae EGD-AQ6 showed utilization of chloroaromatic compound, 2-4-dichlorophenoxyacetic acid (2,4-D) efficiently in its biofilm phenotype. The differential rates of accumulation of intermediate metabolite 4-chlorocatechol (4-CCA) were significant in both planktonic and biofilm phenotypes; also increased number of biofilm cells were observed during 2,4-D utilization. Interestingly, response surface analysis demonstrated the combined positive effects of 2,4-D degradation and 4-CCA accumulations. Also, gene expression profiles showed significant up-regulation of degradative and biofilm genes (particularly pellicle forming genes) in the biofilm phenotypes than their planktonic counterparts, thereby confirming occurrence of phenotype variations of Pseudomonas simiae EGD-AQ6 during chloroaromatic degradation. Furthermore, the sequence similarity of the 2-4-D catabolic genes and biofilm forming proteins (pel ABCDEFG and pga ABCD) which are responsible for building carbohydrate rich extracellular matrix, were significant with the respective organisms as revealed through genome analysis. This is the first report, which endorses this Pseudomonas simiae species to be unique in chloro-aromatic degradation through phenotype variation, thereby proving as a potential candidate in the improvement of bioremediation technologies.

scholarly journals Understanding the Modus Operandi of MicroRNA Regulatory Clusters

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1103 ◽  
Author(s):  
Arthur C. Oliveira ◽  
Luiz A. Bovolenta ◽  
Lucas Alves ◽  
Lucas Figueiredo ◽  
Amanda O. Ribeiro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Modus Operandi ◽  
Wide Range

MicroRNAs (miRNAs) are non-coding RNAs that regulate a wide range of biological pathways by post-transcriptionally modulating gene expression levels. Given that even a single miRNA may simultaneously control several genes enrolled in multiple biological functions, one would expect that these tiny RNAs have the ability to properly sort among distinctive cellular processes to drive protein production. To test this hypothesis, we scrutinized previously published microarray datasets and clustered protein-coding gene expression profiles according to the intensity of fold-change levels caused by the exogenous transfection of 10 miRNAs (miR-1, miR-7, miR-9, miR-124, miR-128a, miR-132, miR-133a, miR-142, miR-148b, miR-181a) in a human cell line. Through an in silico functional enrichment analysis, we discovered non-randomic regulatory patterns, proper of each cluster identified. We demonstrated that miRNAs are capable of equivalently modulate the expression signatures of target genes in regulatory clusters according to the biological function they are assigned to. Moreover, target prediction analysis applied to ten vertebrate species, suggest that such miRNA regulatory modus operandi is evolutionarily conserved within vertebrates. Overall, we discovered a complex regulatory cluster-module strategy driven by miRNAs, which relies on the controlled intensity of the repression over distinct targets under specific biological contexts. Our discovery helps to clarify the mechanisms underlying the functional activity of miRNAs and makes it easier to take the fastest and most accurate path in the search for the functions of miRNAs in any distinct biological process of interest.

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