Inhibition of the biosynthesis of sterols by phenyl and phenolic compounds in rat liver.
Ontology highlight
ABSTRACT:
SUBMITTER: Ranganathan S
PROVIDER: S-EPMC1177870 | biostudies-other | 1973 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Generation of H2O2 by rat liver mitochondria with choline, glycerol 1-phosphate and proline as substrates has been shown by using high-concentration phosphate buffer. Rates obtained under these conditions were higher and more consistent as compared with the earlier reports with high-concentration mannitol/sucrose/Tris buffer. Sulphate ions could replace phosphate indicating a requirement for a high concentration of oxygen-containing anions. H2O2 generation was dependent on the presence of native mitochondria and substrate. Maximal rates with various substrates were found to be the same as with succinate. Values of Km and Vmax for H2O2 generation were considerably less than those obtained for respective dehydrogenase activities, measured by dye reduction. Scavengers of O2-. and OH. inhibited generation of H2O2. ATP, ADP, thyronine derivatives and a number of phenolic compounds also showed very potent inhibitory effects of H2O2 generation, whereas phenyl compound had no effect. Phenolic compounds did not have any effect on mitochondrial superoxide dismutase and choline dehydrogenase activities as well as on O2-. generation by the xanthine-xanthine oxidase system. Inhibition by phenolic compounds may have potential for regulation of the intracellular concentration of H2O2, that is not considered to have a "second messenger' function.
| S-EPMC1162798 | biostudies-other
Project description:Dipeptidyl peptidase IV (DPP IV) is a surface glycoprotein that can degrade glucagon like pepetide-1 (GLP-1) by decreasing blood sugar. Herbal medicines for diabetic therapy are widely used with acceptable efficacy but unsatisfied in advances. DPP IV was chosen as a template to employ molecular docking via Discovery Studio to search for natural phenolic compounds whether they have the inhibitory function of DPP IV. Then, docking candidates were validated and further performed signal pathway via Caco-2, C2C12, and AR42J cells. Lastly, a diet-induced diabetes in mice were applied to examine the efficacy and toxicity of hit natural phenolic products in long-term use (in vivo). After screening, curcumin, syringic acid, and resveratrol were found in high affinity with DPP IV enzymes. In enzymatic tests, curcumin and resveratrol showed potential inhibition of DPP IV. In vitro assays, curcumin inhibited of DPP IV activity in Caco-2 cells and ERK phosphorylation in C2C12 cells. Additionally, curcumin attenuated blood sugar in S961-treated C57BL/6 mice and in diet-induced diabetic ICR mice and long-term regulate HbA1c in diabetic mice. Curcumin targeted to DPP IV for reducing blood glucose, it possesses potential and alternative substitution of synthetic clinical drugs for the medication of diabetes.
| S-EPMC6821704 | biostudies-literature
Project description:Sophorae Radix (Sophora flavescens Aiton) has long been used in traditional medicine in East Asia due to the various biological activities of its secondary metabolites. Endogenous contents of phenolic compounds (phenolic acid, flavonol, and isoflavone) and the main bioactive compounds of Sophorae Radix were analyzed based on the qualitative HPLC analysis and evaluated in different organs and at different developmental stages. In total, 11 compounds were detected, and the composition of the roots and aerial parts (leaves, stems, and flowers) was significantly different. trans-Cinnamic acid and p-coumaric acid were observed only in the aerial parts. Large amounts of rutin and maackiain were detected in the roots. Four phenolic acid compounds (benzoic acid, caffeic acid, ferulic acid, and chlorogenic acid) and four flavonol compounds (kaempferol, catechin hydrate, epicatechin, and rutin) were higher in aerial parts than in roots. To identify putative genes involved in phenolic compounds biosynthesis, a total of 41 transcripts were investigated. Expression patterns of these selected genes, as well as the multiple isoforms for the genes, varied by organ and developmental stage, implying that they are involved in the biosynthesis of various phenolic compounds both spatially and temporally.
| S-EPMC5852875 | biostudies-literature
Project description:Polyphenols in whole grain wheat have potential health benefits, but little is known about the expression patterns of phenolic acid biosynthesis genes and the accumulation of phenolic acid compounds in different-colored wheat grains. We found that purple wheat varieties had the highest total phenolic content (TPC) and antioxidant activity. Among phenolic acid compounds, bound ferulic acid, vanillic, and caffeic acid levels were significantly higher in purple wheat than in white and red wheat, while total soluble phenolic acid, soluble ferulic acid, and vanillic acid levels were significantly higher in purple and red wheat than in white wheat. Ferulic acid and syringic acid levels peaked at 14 days after anthesis (DAA), whereas p-coumaric acid and caffeic acid levels peaked at 7 DAA, and vanillic acid levels gradually increased during grain filling and peaked near ripeness (35 DAA). Nine phenolic acid biosynthesis pathway genes (TaPAL1, TaPAL2, TaC3H1, TaC3H2, TaC4H, Ta4CL1, Ta4CL2, TaCOMT1, and TaCOMT2) exhibited three distinct expression patterns during grain filling, which may be related to the different phenolic acids levels. White wheat had higher phenolic acid contents and relatively high gene expression at the early stage, while purple wheat had the highest phenolic acid contents and gene expression levels at later stages. These results suggest that the expression of phenolic acid biosynthesis genes may be closely related to phenolic acids accumulation.
| S-EPMC4840273 | biostudies-literature
Project description:Vitiligo, an acquired disorder characterized by depigmented skin patches, results from loss of epidermal melanocytes. Etiology of vitiligo is not clearly understood but environmental, biochemical, genetic, and immune factors play a role in its pathogenesis. There is evidence that melanocyte death is perpetuated by an autoimmune response that causes lesions to spread. 4-tertiary butyl phenol (4TBP) and monobenzyl ether of hydroquinone (MBEH) are phenolic compounds that are known as environmental causes of vitiligo. We used microarray to detail the global gene expression that occurs following exposure of melanocytes to 4-TBP or MBEH to identified distinct classes of up-regulated genes that may contribute to melanocyte loss in vitiligo. We show that human melanocytes exposed to 4-TBP and MBEH show increased production of some inflammatory cytokines. Interleukin-6 (IL6) and IL8, in particular, are expressed at the periphery of vitiligo lesions and may contribute to recruitment of immune components to the areas, perpetuating melanocyte loss. Cultured human epidermal melanocytes were treated with 4TBP or MBEH for 3, 6, or 24 hours and gene expression were compared with untreated cells.
2012-12-01 | E-GEOD-31641 | biostudies-arrayexpress
Project description:Vitiligo, an acquired disorder characterized by depigmented skin patches, results from loss of epidermal melanocytes. Etiology of vitiligo is not clearly understood but environmental, biochemical, genetic, and immune factors play a role in its pathogenesis. There is evidence that melanocyte death is perpetuated by an autoimmune response that causes lesions to spread. 4-tertiary butyl phenol (4TBP) and monobenzyl ether of hydroquinone (MBEH) are phenolic compounds that are known as environmental causes of vitiligo. We used microarray to detail the global gene expression that occurs following exposure of melanocytes to 4-TBP or MBEH to identified distinct classes of up-regulated genes that may contribute to melanocyte loss in vitiligo. We show that human melanocytes exposed to 4-TBP and MBEH show increased production of some inflammatory cytokines. Interleukin-6 (IL6) and IL8, in particular, are expressed at the periphery of vitiligo lesions and may contribute to recruitment of immune components to the areas, perpetuating melanocyte loss.
2012-12-01 | GSE31641 | GEO
Project description:Two new sucrose derivatives, namely, belamcanosides A (1) and B (2), together with five other known compounds (3-7), were isolated from the seeds of Belamcanda chinensis (L.) DC. Their structures were identified based on spectroscopic data. Especially, the absolute configurations of fructose and glucose residues in 1 and 2 were assigned by acid hydrolysis, followed by derivatization and gas chromatography (GC) analysis. Among the known compounds, (-)-hopeaphenol (3), (+)-syringaresinol (4), and quercetin (5), were isolated from B. chinensis for the first time. In addition, biological evaluation of 1 and 2 against cholesterol synthesis and metabolism at the gene level was carried out. The results showed that compounds 1 and 2 could regulate the expression of cholesterol synthesis and metabolism-associated genes, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), squalene epoxidase (SQLE), low density lipoprotein receptor (LDLR), and sortilin (SORT1) genes in HepG2 cells.
| S-EPMC6017503 | biostudies-other
Project description:Pyrraline, a typical kind of advanced glycation end product, has been found to contribute to the development of pathologies associated with ageing and diabetes mellitus. In the study, phenolic compounds extracted from highland barley whole grain (HBWG) and vinasse (HBVN) were used to inhibit pyrraline formation in a simulated food. The optimal extraction condition for HBWG and HBVN was using 8 mL of 50% acetone solution at 50 °C for 60 min. The extraction and identification of phenolic compounds from HBWG and HBVN were performed by UPLC-PAD-MS/MS. The inhibitory effects of pyrraline in the simulated food were 52.03% and 49.22% by HBVN and HBWG, respectively. The diphenyl picrylhydrazyl radical- and ferric-reducing ability of plasma assays was used to evaluate the antioxidant activity of the extracts. The main inhibition pathways and molecular mechanism of phenolic compounds on pyrraline regulation were explored by scavenging α-dicarbonyl compounds. The study demonstrated that highland barley and its by-products can potentially be used as a functional food to regulate pyrraline formation during food processing.
| S-EPMC8156036 | biostudies-literature
Project description:1. [2-(14)C]Mevalonate was incorporated into squalene and the major phytosterols of pea and maize leaves; it was also incorporated into compounds belonging to the 4,4-dimethyl and 4alpha-methyl steroid groups and which may be possible phytosterol intermediates. 2. l-[Me-(14)C]Methionine was incorporated into the major sterols and also into the 4,4-dimethyl and 4alpha-methyl steroid groups. No radioactivity was detected in squalene. 3. Under anaerobic conditions incorporation of [2-(14)C]-mevalonate into the non-saponifiable lipid of pea leaves was drastically decreased but radioactive squalene was accumulated. 4. Cycloartenol, 24-methylenecycloartanol, 24-methylenelophenol, 24-ethylidenelophenol, fucosterol, beta-sitosterol, stigmasterol and campesterol have been identified by gas-liquid chromatography in pea leaves. 5. The significance of these results in connexion with phytosterol biosynthesis and the introduction of the alkyl group at C-24 into phytosterols is discussed.
| S-EPMC1265065 | biostudies-other
Project description:Vibrio parahaemolyticus (Vp), a typical microorganism inhabiting marine ecosystems, uses pathogenic virulence molecules such as hemolysins to cause bacterial infections of both human and marine animals. The thermolabile hemolysin VpTLH lyses human erythrocytes by a phospholipase B/A2 enzymatic activity in egg-yolk lecithin. However, few studies have been characterized the biochemical properties and the use of VpTLH as a molecular target for natural compounds as an alternative to control Vp infection. Here, we evaluated the biochemical and inhibition parameters of the recombinant VpTLH using enzymatic and hemolytic assays and determined the molecular interactions by in silico docking analysis. The highest enzymatic activity was at pH 8 and 50 °C, and it was inactivated by 20 min at 60 °C with Tm = 50.9 °C. Additionally, the flavonoids quercetin, epigallocatechin gallate, and morin inhibited the VpTLH activity with IC50 values of 4.5 µM, 6.3 µM, and 9.9 µM, respectively; while phenolics acids were not effective inhibitors for this enzyme. Boltzmann and Arrhenius equation analysis indicate that VpTLH is a thermolabile enzyme. The inhibition of both enzymatic and hemolytic activities by flavonoids agrees with molecular docking, suggesting that flavonoids could interact with the active site's amino acids. Future research is necessary to evaluate the antibacterial activity of flavonoids against Vp in vivo.
| S-EPMC7796666 | biostudies-literature