Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives

Urbatzka, Ralph; Freitas, Sara; Palmeira, Andreia; Almeida, Tiago; Moreira, João Paulo Carvalho; Azevedo, Carlos Lima; Afonso, Carlos; Correia-da-Silva, Marta; Sousa, Emı́lia; Pinto, Madalena; Vasconcelos, Vı́tor

doi:10.1016/j.ejmech.2018.03.036

Cited by 34 publications

(44 citation statements)

References 37 publications

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“…Our work evidenced the lipid-reducing activity of some extracts (EL, ML) with EC 50 values of 1.2-2.2 µg/mL using the zebrafish Nile red fat metabolism assay as a whole small animal model in vivo. This assay was used previously to show the lipid-lowering effects of extracts of raw materials or marine organisms (wine lee, actinobacteria, cyanobacteria, sponges), or isolated compounds (polyphenols, chlorophyll derivatives) [19][20][21][22][23]. The original paper from Jones et al [24] demonstrated that zebrafish responded to lipid modulator drugs in the same way as humans.…”

Section: Discussionmentioning

confidence: 99%

“…Castro et al [27] reported that plants are the main source of natural compounds with anti-obesity properties, and the majority of these compounds belong to the phenols and polyphenols class. The screening of a library of polyphenol derivatives identified compounds with strong lipid reducing activity in the zebrafish Nile red fat metabolism assay [20]. The naphthoquinone shikonin (5,6-dihydroxyflavone-7-glucuronic acid), a compound isolated from the Japanese plant Lithospermum erythrorhizon, inhibited fat accumulation in 3T3-L1 adipocytes [28].…”

Section: Discussionmentioning

confidence: 99%

“…Lipid-reducing activity of the different extracts was analyzed with the zebrafish Nile red fat metabolism assay, as described in [20]. Zebrafish adults and larvae were maintained under standard conditions at 28 • C. In brief, zebrafish embryos were raised from 1 DPF (days post-fertilization) in egg water (60 µg/mL marine sea salt dissolved in distilled H 2 O) with 200 µM PTU (1-phenyl-2-thiourea) to inhibit pigmentation.…”

Section: Zebrafish Nile Red Fat Metabolism Assaymentioning

confidence: 99%

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The Marine Seagrass Halophila stipulacea as a Source of Bioactive Metabolites against Obesity and Biofouling

et al. 2020

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Marine organisms, including seagrasses, are important sources of biologically active molecules for the treatment of human diseases. In this study, organic extracts of the marine seagrass Halophila stipulacea obtained by different polarities from leaves (L) and stems (S) (hexane [HL, HS], ethyl acetate [EL, ES], and methanol [ML, MS]) were tested for different bioactivities. The screening comprehended the cytotoxicity activity against cancer cell lines grown as a monolayer culture or as multicellular spheroids (cancer), glucose uptake in cells (diabetes), reduction of lipid content in fatty acid-overloaded liver cells (steatosis), and lipid-reducing activity in zebrafish larvae (obesity), as well as the antifouling activity against marine bacteria (microfouling) and mussel larval settlement (macrofouling). HL, EL, HS, and ES extracts showed statistically significant cytotoxicity against cancer cell lines. The extracts did not have any significant effect on glucose uptake and on the reduction of lipids in liver cells. The EL and ML extracts reduced neutral lipid contents on the larvae of zebrafish with EC50 values of 2.2 µg/mL for EL and 1.2 µg/mL for ML. For the antifouling activity, the HS and ML extracts showed a significant inhibitory effect (p < 0.05) against the settlement of Mytilus galloprovincialis plantigrade larvae. The metabolite profiling using HR-LC-MS/MS and GNPS (The Global Natural Product Social Molecular Networking) analyses identified a variety of known primary and secondary metabolites in the extracts, along with some unreported molecules. Various compounds were detected with known activities on cancer (polyphenols: Luteolin, apeginin, matairesinol), on metabolic diseases (polyphenols: cirsimarin, spiraeoside, 2,4-dihydroxyheptadec-16-ynyl acetate; amino acids: N-acetyl-L-tyrosine), or on antifouling (fatty acids: 13-decosenamide; cinnamic acids: 3-hydroxy-4-methoxycinnamic acid, alpha-cyano-4-hydroxycinnamic), which could be, in part, responsible for the observed bioactivities. In summary, this study revealed that Halophila stipulacea is a rich source of metabolites with promising activities against obesity and biofouling and suggests that this seagrass could be useful for drug discovery in the future.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Zebrafish Nile Red Fat Metabolism Assaymentioning

confidence: 99%

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The Marine Seagrass Halophila stipulacea as a Source of Bioactive Metabolites against Obesity and Biofouling

et al. 2020

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“…In fact, with proper synthetic pathways, many other substituents can be introduced into the xanthone scaffold affording the development of more diverse compounds for biological activity and structure-activity relationship (SAR) studies [18], as well as other applications such as preparation of fluorescence probes [19,20] or stationary phases for liquid chromatography [21,22,23]. For the last several years, the isolation and synthesis of new bioactive xanthone derivatives using different synthetic methodologies has remained in the area of great interest of our group, as exemplified in [24,25,26,27,28,29,30,31,32,33,34,35].…”

Section: Introductionmentioning

confidence: 99%

Carboxyxanthones: Bioactive Agents and Molecular Scaffold for Synthesis of Analogues and Derivatives

et al. 2019

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Xanthones represent a structurally diverse group of compounds with a broad range of biological and pharmacological activities, depending on the nature and position of various substituents in the dibenzo-γ-pyrone scaffold. Among the large number of natural and synthetic xanthone derivatives, carboxyxanthones are very interesting bioactive compounds as well as important chemical substrates for molecular modifications to obtain new derivatives. A remarkable example is 5,6-dimethylxanthone-4-acetic acid (DMXAA), a simple carboxyxanthone derivative, originally developed as an anti-tumor agent and the first of its class to enter phase III clinical trials. From DMXAA new bioactive analogues and derivatives were also described. In this review, a literature survey covering the report on carboxyxanthone derivatives is presented, emphasizing their biological activities as well as their application as suitable building blocks to obtain new bioactive derivatives. The data assembled in this review intends to highlight the therapeutic potential of carboxyxanthone derivatives and guide the design for new bioactive xanthone derivatives.

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“…Polyphenols are important natural substances with pronounced antioxidative properties [5] that enable them to regulate oxidative stress in living organisms [6]. These phytochemicals possess a strong lipid-reducing activity [7], which promotes weight maintenance and provides a tool for an effective therapy for obesity and oxidative stress [8,9]. Considering that lipid peroxidation is a direct consequence of oxidative stress, adequate supplementation with antioxidants is desirable.…”

Section: Introductionmentioning

confidence: 99%

A Micromethod for Polyphenol High-Throughput Screening Saves 90 Percent Reagents and Sample Volume

et al. 2019

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There is ample evidence that polyphenols are important natural substances with pronounced antioxidative properties. This study aimed to develop a fast and reliable method to determine total polyphenol content (TPC) in foodstuffs and human samples. The microtitration format offers the advantage of low sample volumes in the microlitre range, facilitating high-throughput screening with 40 samples simultaneously. We accordingly adjusted the so-called Folin–Ciocalteu method to a microtitre format (polyphenols microtitre—PPm) with 90% reduction of reagents. The assay was standardized with gallic acid in the range between 0.1 and 3 mM, using a 20 µL sample volume. The intra-assay coefficient of variation (CV) was less than 5%, and inter-assay CV was in the range of 10%. Wavelength was measured at 766 nm after two hours of incubation. This micromethod correlates significantly with both the classical Folin–Ciocalteu method and High-Performance Thin-Layer Chromatography (HPTLC) (r2 = 0.9829). We further observed a significant correlation between PPm and total antioxidants (r2 = 0.918). The highest polyphenol concentrations were obtained for red, blue, and black fruits, vegetables, and juices. Extracts of red grapes could be harvested almost sugar free and might serve as a basis for polyphenol supplementation. Beer, flour, and bread contained polyphenol concentrations sufficient to meet the minimal daily requirement. We conclude that PPm is a sensitive and reliable method that detects polyphenols even in samples diluted 10-fold. The literature strongly recommends further investigations on the effects of polyphenol uptake on human and animal health.

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Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives

Cited by 34 publications

References 37 publications

The Marine Seagrass Halophila stipulacea as a Source of Bioactive Metabolites against Obesity and Biofouling

The Marine Seagrass Halophila stipulacea as a Source of Bioactive Metabolites against Obesity and Biofouling

Carboxyxanthones: Bioactive Agents and Molecular Scaffold for Synthesis of Analogues and Derivatives

A Micromethod for Polyphenol High-Throughput Screening Saves 90 Percent Reagents and Sample Volume

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