Untargeted metabolomic study of HepG2 cells under the effect of <scp><i>Fucus vesiculosus</i></scp> aqueous extract

André, Rebeca; Guedes, Rita; López, Javier; Serralheiro, Maria Luísa

doi:10.1002/rcm.9197

Cited by 8 publications

(22 citation statements)

References 27 publications

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“…In the cells treated with Aramé extract, a decrease in the level of GSH was detected relative to the control cells, which can be associated with a higher utilization rate of this metabolite inside the treated cells, a mechanism important to prevent oxidative stress. A modification in glutathione metabolism was seen in Hep-G2 cells exposed to a brown seaweed Fucus vesiculosus extract [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

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Anti-Hypercholesterolemia Effects of Edible Seaweed Extracts and Metabolomic Changes in Hep-G2 and Caco-2 Cell Lines

Coelho

Pacheco

2023

Life

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Hypercholesterolemia is a major risk for the development of cardiovascular diseases (CVDs), the main cause of mortality worldwide, and it is characterized by high levels of circulating cholesterol. The drugs currently available for hypercholesterolemia control have several side effects, so it is necessary to develop new effective and safer therapies. Seaweeds serve as sources of several bioactive compounds with claimed beneficial effects. Eisenia bicyclis (Aramé) and Porphyra tenera (Nori) are edible seaweeds that were previously recognized as rich in bioactive compounds. In the present study, we aim to evaluate the anti-hypercholesterolemia effect of these two seaweed extracts and their health potential. Both extracts, but more efficiently Aramé extract, have liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitory activity as well as the capability to reduce approximately 30% of cholesterol permeation through human Caco-2 cells by simulating the intestinal lining, which is a target for hypercholesterolemia treatments. An untargeted metabolomic assay on human intestinal Caco-2 and liver Hep-G2 cell lines exposed to Aramé and Nori extracts revealed changes in the cells’ metabolism, indicating the extracts’ health beneficial effects. The metabolic pathways affected by exposure to both extracts were associated with lipid metabolism, such as phospholipids, and fatty acid metabolism, amino acid pathways, cofactors, vitamins, and cellular respiration metabolism. The effects were more profound in Aramé-treated cells, but they were also observed in Nori-exposed cells. The metabolite modifications were associated with the protection against CVDs and other diseases and to the improvement of the cells’ oxidative stress tolerance. The results obtained for the anti-hypercholesterolemia properties, in addition to the revelation of the positive impact on cell metabolism, offer an important contribution for further evaluation of these seaweed extracts as functional foods or for CVD prevention.

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Section: Resultsmentioning

confidence: 99%

“…Both of these types of metabolites may be related to modifications in the metabolism of lipids, proteins, and amino acids due to exposure to the Nori extract. In the case of fatty acid amides, it was already reported that Hep-G2 metabolites were modified by a Fucus vesiculosus extract [ 60 ].…”

Section: Resultsmentioning

confidence: 99%

Anti-Hypercholesterolemia Effects of Edible Seaweed Extracts and Metabolomic Changes in Hep-G2 and Caco-2 Cell Lines

Coelho

Pacheco

2023

Life

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“…For example, decanamide is only referred to as a minor metabolite of the bacterium Pseudomonas X2 when grown with n-decane as its only carbon source [ 36 ]. In contrast, dodecanamide, palmitamide, stearamide, oleamide, and linoleamide were all produced by HepG2 cells treated with extracts of the brown algae Fucus vesiculosus [ 37 ]. Dodecanamide has been reported as an intracellular metabolite in MCF-7 cells after doxorubicin-induced cell death [ 38 ] and with diminished levels in the serum of acute myeloid leukemia patients who responded well to chemotherapy with cytarabine plus anthracycline [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Dodecanamide has been reported as an intracellular metabolite in MCF-7 cells after doxorubicin-induced cell death [ 38 ] and with diminished levels in the serum of acute myeloid leukemia patients who responded well to chemotherapy with cytarabine plus anthracycline [ 39 ]. There exist more extensive studies in the literature on palmitamide, palmitoleamide, stearamide, oleamide, and linoleamide [ 37 , 40 , 41 , 42 , 43 , 44 ], but none in relation to HCV and the liver, with the exception of oleamide in our earlier metabolomics report on HCV-infected patients [ 28 ]. Therefore, our description of these seven FAAs elevated due to HCV infection is novel, which is additionally supported by our observation that the FAA catabolic enzyme FAAH2 showed a 40% decrease ( p = 0.03) in mRNA expression due to HCV.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Infection Upregulates Plasma Phosphosphingolipids and Endocannabinoids and Downregulates Lysophosphoinositols

Beyoğlu

Schwalm

Semmo

et al. 2023

IJMS

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A mass spectrometry-based lipidomic investigation of 30 patients with chronic hepatitis C virus (HCV) infection and 30 age- and sex-matched healthy blood donor controls was undertaken. The clustering and complete separation of these two groups was found by both unsupervised and supervised multivariate data analyses. Three patients who had spontaneously cleared the virus and three who were successfully treated with direct-acting antiviral drugs remained within the HCV-positive metabotype, suggesting that the metabolic effects of HCV may be longer-lived. We identified 21 metabolites that were upregulated in plasma and 34 that were downregulated (p < 1 × 10−16 to 0.0002). Eleven members of the endocannabinoidome were elevated, including anandamide and eight fatty acid amides (FAAs). These likely activated the cannabinoid receptor GPR55, which is a pivotal host factor for HCV replication. FAAH1, which catabolizes FAAs, reduced mRNA expression. Four phosphosphingolipids, d16:1, d18:1, d19:1 sphingosine 1-phosphate, and d18:0 sphinganine 1-phosphate, were increased, together with the mRNA expression for their synthetic enzyme SPHK1. Among the most profoundly downregulated plasma lipids were several lysophosphatidylinositols (LPIs) from 3- to 3000-fold. LPIs are required for the synthesis of phosphatidylinositol 4-phosphate (PI4P) pools that are required for HCV replication, and LPIs can also activate the GPR55 receptor. Our plasma lipidomic findings shed new light on the pathobiology of HCV infection and show that a subset of bioactive lipids that may contribute to liver pathology is altered by HCV infection.

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“…30 The reported activities did coincide with the clinical efficacy of CNL granule. Kaempferol-7-O-neohesperidoside was tested for antitumor activity and exhibited potent activities against HepG2 31 and Hela 32 with IC 50 values of 0.020 and 0.051 μM, respectively. Given its potent toxicity against tumor cells, its toxicity toward normal human cells is to be tested before these analogues can be taken as the bioactive material basis of CNL granule.…”

Section: Chemical Constituent Comparison Between the Two Extractsmentioning

confidence: 99%

Profiling aromatic constituents of Chimonanthus nitens Oliv. leaf granule using mass spectrometry

Zou

Yang

Wang

et al. 2023

Rapid Comm Mass Spectrometry

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Rationale The chemical constituents of Chinese patent medicine are usually different from those of crude medicine because of specific preparation processes. Chimonanthus nitens Oliv. leaf granule is widely used for prevention against COVID‐19 in China. However, no research has been reported on the chemical constituents of the granule and their variation during the preparation process. Methods Fragmentation patterns of reference compounds were investigated using electrospray ionization mass spectrometry, and the new gas‐phase reaction was demonstrated by electronic and steric effects and calculated chemistry. Then, a strategy based on new fragmentation patterns was used to profile aromatic constituents. In addition, based on untargeted metabolomics analytical workflow, a comparison was made on the chemical constituents of the leaf and granule. Results New fragmentation patterns related to two competing reactions, ring‐opening and ring‐closing reactions for coumarin, have been proposed and investigated in depth. The newly established diagnostic ion at m/z 81.0331 worked strongly in the assignment of OH‐7 and substituent at C‐8 of coumarin. McLafferty rearrangement occurring in coumarin glycoside while sugar group locating at C‐4 was first observed, and new diagnostic ions at m/z 147.0440, 119.0488, and 91.0543 were constructed. Conclusions Aromatic constituents of the granule were first profiled. A total of 114 aromatic compounds were identified; of these 85 compounds were identified first. Kaempferol‐7‐O‐neohesperidoside and its homologues were mostly enriched in the granule. Considering their reported bioactivities, these analogues possibly contribute greatly to clinical efficacy. Our results provided a new fragmentation theory for coumarins and a new material basis for the quality control of the granule.

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Untargeted metabolomic study of HepG2 cells under the effect of Fucus vesiculosus aqueous extract

Cited by 8 publications

References 27 publications

Anti-Hypercholesterolemia Effects of Edible Seaweed Extracts and Metabolomic Changes in Hep-G2 and Caco-2 Cell Lines

Anti-Hypercholesterolemia Effects of Edible Seaweed Extracts and Metabolomic Changes in Hep-G2 and Caco-2 Cell Lines

Hepatitis C Virus Infection Upregulates Plasma Phosphosphingolipids and Endocannabinoids and Downregulates Lysophosphoinositols

Profiling aromatic constituents of Chimonanthus nitens Oliv. leaf granule using mass spectrometry

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