scholarly journals Effects of the Phytochemical Combination PB123 on Nrf2 Activation, Gene Expression, and the Cholesterol Pathway in HepG2 Cells

2021 ◽  
Vol 7 (1) ◽  
pp. 1-1
Author(s):  
Brooks M. Hybertson ◽  
◽  
Bifeng Gao ◽  
Joe M. McCord ◽  
◽  
...  
Keyword(s):  
Gene Expression ◽  
Dietary Supplement ◽  
Hepg2 Cells ◽  
Cholesterol Biosynthesis ◽  
Cumene Hydroperoxide ◽  
Zingiber Officinale ◽  
Biologically Active ◽  
Related Factor ◽  
Sophora Japonica ◽  
Plant Materials

There has been a long history of human usage of the biologically-active phytochemicals in Salvia rosmarinus, Zingiber officinale, and Sophora japonica for health purposes, and we recently reported on a combination of those plant materials as the PB123 dietary supplement. In the present work we extended those studies to evaluate activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor and differential gene expression in cultured HepG2 (hepatocellular carcinoma) cells treated with PB123. We determined transcriptome changes using mRNA-seq methods, and analyzed the affected pathways using Ingenuity Pathway Analysis and BioJupies, indicating that primary effects included increasing the Nrf2 pathway and decreasing the cholesterol biosynthesis pathway. Pretreatment of cultured HepG2 cells with PB123 upregulated Nrf2-dependent cytoprotective genes and increased cellular defenses against cumene hydroperoxide-induced oxidative stress. In contrast, pretreatment of cultured HepG2 cells with PB123 downregulated cholesterol biosynthesis genes and decreased cellular cholesterol levels. These findings support the possible beneficial effects of PB123 as a healthspan-promoting dietary supplement.

scholarly journals Phytochemical Combination PB125 Activates the Nrf2 Pathway and Induces Cellular Protection against Oxidative Injury

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 119 ◽  
Author(s):  
Brooks M. Hybertson ◽  
Bifeng Gao ◽  
Swapan Bose ◽  
Joe M. McCord
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Dietary Supplement ◽  
Withania Somnifera ◽  
Rosmarinus Officinalis ◽  
Carnosic Acid ◽  
Withaferin A ◽  
Related Factor ◽  
Sophora Japonica ◽  
Nrf2 Pathway

Bioactive phytochemicals in Rosmarinus officinalis, Withania somnifera, and Sophora japonica have a long history of human use to promote health. In this study we examined the cellular effects of a combination of extracts from these plant sources based on specified levels of their carnosol/carnosic acid, withaferin A, and luteolin levels, respectively. Individually, these bioactive compounds have previously been shown to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, which binds to the antioxidant response element (ARE) and regulates the expression of a wide variety of cytoprotective genes. We found that combinations of these three plant extracts act synergistically to activate the Nrf2 pathway, and we identified an optimized combination of the three agents which we named PB125 for use as a dietary supplement. Using microarray, quantitative reverse transcription-PCR, and RNA-seq technologies, we examined the gene expression induced by PB125 in HepG2 (hepatocellular carcinoma) cells, including canonical Nrf2-regulated genes, noncanonical Nrf2-regulated genes, and genes which appear to be regulated by non-Nrf2 mechanisms. Ingenuity Pathway Analysis identified Nrf2 as the primary pathway for gene expression changes by PB125. Pretreatment with PB125 protected cultured HepG2 cells against an oxidative stress challenge caused by cumene hydroperoxide exposure, by both cell viability and cell injury measurements. In summary, PB125 is a phytochemical dietary supplement comprised of extracts of three ingredients, Rosmarinus officinalis, Withania somnifera, and Sophora japonica, with specified levels of carnosol/carnosic acid, withaferin A, and luteolin, respectively. Each ingredient contributes to the activation of the Nrf2 pathway in unique ways, which leads to upregulation of cytoprotective genes and protection of cells against oxidative stress and supports the use of PB125 as a dietary supplement to promote healthy aging.

scholarly journals Some Common Medicinal Plants with Antidiabetic Activity, Known and Available in Europe (A Mini-Review)

2022 ◽  
Vol 15 (1) ◽  
pp. 65
Author(s):  
Monika Przeor
Keyword(s):  
Raw Materials ◽  
Antioxidant Properties ◽  
Zingiber Officinale ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Antidiabetic Activity ◽  
Plant Materials ◽  
Trigonella Foenum Graecum L

Diabetes is a metabolic disease that affected 9.3% of adults worldwide in 2019. Its co-occurrence is suspected to increase mortality from COVID-19. The treatment of diabetes is mainly based on the long-term use of pharmacological agents, often expensive and causing unpleasant side effects. There is an alarming increase in the number of pharmaceuticals taken in Europe. The aim of this paper is to concisely collect information concerning the few antidiabetic or hypoglycaemic raw plant materials that are present in the consciousness of Europeans and relatively easily accessible to them on the market and sometimes even grown on European plantations. The following raw materials are discussed in this mini-review: Morus alba L., Cinnamomum zeylanicum J.Presl, Trigonella foenum-graecum L., Phaseolus vulgaris L., Zingiber officinale Rosc., and Panax ginseng C.A.Meyer in terms of scientifically tested antidiabetic activity and the presence of characteristic biologically active compounds and their specific properties, including antioxidant properties. The characteristics of these raw materials are based on in vitro as well as in vivo studies: on animals and in clinical studies. In addition, for each plant, the possibility to use certain morphological elements in the light of EFSA legislation is given.

Cell-specific regulation of IRS-1 gene expression: role of E box and C/EBP binding site in HepG2 cells and CHO cells

Diabetes ◽  
1997 ◽  
Vol 46 (3) ◽  
pp. 354-362 ◽  
Author(s):  
K. Matsuda ◽  
E. Araki ◽  
R. Yoshimura ◽  
K. Tsuruzoe ◽  
N. Furukawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Site ◽  
Cho Cells ◽  
Hepg2 Cells ◽  
E Box ◽  
Specific Regulation

scholarly journals High-throughput transcriptomic analysis of human primary hepatocyte spheroids exposed to per- and polyfluoroalkyl substances (PFAS) as a platform for relative potency characterization

2021 ◽  
Author(s):  
A Rowan-Carroll ◽  
A Reardon ◽  
K Leingartner ◽  
R Gagné ◽  
A Williams ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cholesterol Biosynthesis ◽  
Health Hazard ◽  
Biological Responses ◽  
Similar Gene Expression Profile ◽  
Transcriptional Changes ◽  
Hazard And Risk ◽  
Hepatocyte Spheroids ◽  
Similar Gene ◽  
Identify Gene Expression

Abstract Per- and poly-fluoroalkyl substances (PFAS) are widely found in the environment because of their extensive use and persistence. Although several PFAS are well studied, most lack toxicity data to inform human health hazard and risk assessment. This study focussed on four model PFAS: perfluorooctanoic acid (PFOA; 8 carbon), perfluorobutane sulfonate (PFBS; 4 carbon), perfluorooctane sulfonate (PFOS; 8 carbon), and perfluorodecane sulfonate (PFDS; 10 carbon). Human primary liver cell spheroids (pooled from 10 donors) were exposed to 10 concentrations of each PFAS and analyzed at four time-points. The approach aimed to: (1) identify gene expression changes mediated by the PFAS; (2) identify similarities in biological responses; (3) compare PFAS potency through benchmark concentration analysis; and (4) derive bioactivity exposure ratios (ratio of the concentration at which biological responses occur, relative to daily human exposure). All PFAS induced transcriptional changes in cholesterol biosynthesis and lipid metabolism pathways, and predicted PPARα activation. PFOS exhibited the most transcriptional activity and had a highly similar gene expression profile to PFDS. PFBS induced the least transcriptional changes and the highest benchmark concentration (i.e., was the least potent). The data indicate that these PFAS may have common molecular targets and toxicities, but that PFOS and PFDS are the most similar. The transcriptomic bioactivity exposure ratios derived here for PFOA and PFOS were comparable to those derived using rodent apical endpoints in risk assessments. These data provide a baseline level of toxicity for comparison with other known PFAS using this testing strategy.

scholarly journals Detoxification and Immune Transcriptomic Response of the Gill Tissue of Bay Scallop (Argopecten irradians) Following Exposure to the Algicide Palmitoleic Acid

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 139 ◽  
Author(s):  
Cheng Chi ◽  
Sib Giri ◽  
Jin Jun ◽  
Hyoun Kim ◽  
Sang Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cytochrome P450 ◽  
Palmitoleic Acid ◽  
Molecular Mechanisms ◽  
Functional Enrichment ◽  
Alexandrium Tamarense ◽  
Read Length ◽  
Related Factor ◽  
Transcriptomic Response ◽  
Bay Scallop

Palmitoleic acid (PA) is an effective algicide against Alexandrium tamarense. However, the toxicological mechanism of PA exposure is unclear. The transcript abundance and differentially expressed genes (DEGs) in gills of bay scallop were investigated following 80 mg/L PA exposure up to 48 h using the Illumina HiSeq 4000 deep-sequencing platform with the recommended read length of 100 bp. De novo assembly of paired-end reads yielded 62,099 unigenes; 5414 genes were identified as being significantly increased, and 4452 were decreased. Based on gene ontology classification and enrichment analysis, the ‘cellular process’, ‘metabolic process’, ‘response to stimulus’, and ‘catalytic process’ with particularly high functional enrichment were revealed. The DEGs, which are related to detoxification and immune responses, revealed that acid phosphatase, fibrinogen C domain-containing protein, cyclic AMP-responsive element-binding protein, glutathione reductase, ATP-binding cassette, nuclear factor erythroid 2-related factor, NADPH2:quinone reductase, and cytochrome P450 4F22, 4B1, and 2C8-related gene expression decreased. In contrast, some genes related to glutathione S-transferase, C-type lectin, superoxide dismutase, toll-like receptors, and cytochrome P450 2C14, 2U1, 3A24 and 4A2 increased. The results of current research will be a valuable resource for the investigation of gene expression stimulated by PA, and will help understanding of the molecular mechanisms underlying the scallops’ response to PA exposure.

scholarly journals Expression of adipocytokine genes and their content in various adipose tissue sites in patients with heart diseases

2020 ◽  
Author(s):  
Olga Gruzdeva ◽  
Yulia Dyleva ◽  
Ekaterina Belik ◽  
Daria Borodkina ◽  
Maxim Sinitsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Coronary Artery Disease ◽  
Adipose Tissue ◽  
Coronary Artery ◽  
Mitral Valve ◽  
Valve Replacement ◽  
Mitral Valve Replacement ◽  
Biologically Active ◽  
Fat Depots ◽  
Artery Disease

Abstract Background Adipose tissue (AT) is an endocrine and paracrine organ that synthesizes biologically active adipocytokines, which affect inflammation, fibrosis, and atherogenesis. Epicardial and perivascular fat depots are of great interest owing to potential effects on the myocardium and blood vessels. Objective To assess expression and secretion of adipocytokine genes in adipose tissue in patients coronary artery disease (CAD) and patients with aortic or mitral valve replacement. Methods The study included 84 patients with CAD and 50 patients with aortic or mitral valve replacement. Adipocytes were isolated from subcutaneous (SAT), epicardial (EAT), and perivascular AT (PVAT) samples. Isolated adipocytes were cultured for 24 h after which, gene expression and secretion levels of selected adipokines and cytokines in the culture medium were determined. Results The study parameters differed depending on the adipose tissue location. EAT adipocytes in CAD patients were characterized by a pronounced imbalance in the adipokine system. EAT had the lowest adiponectin gene expression and secretion, regardless of nosology and high expression levels of the leptin gene, its receptor, and interleukin-6 (IL-6) were detected. High leptin and IL-6 levels resulted in increased pro-inflammatory activity, as observed in both EAT and PVAT adipocytes, especially in individuals with coronary artery disease. Conclusion The "protective" potential of adipose tissue depends on its location.

Sign in / Sign up

Export Citation Format

Share Document