Chlorophyll Derivatives from Marine Cyanobacteria with Lipid-Reducing Activities

Freitas, Sara; Silva, Natália Gonçalves; Sousa, Maria Lígia; Ribeiro, Tiago; Rosa, Filipa; Leão, Pedro N.; Vasconcelos, Vı́tor; Reis, Mariana; Urbatzka, Ralph

doi:10.3390/md17040229

Cited by 39 publications

(31 citation statements)

References 56 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%

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%

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

et al. 2020

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“…The development of the method was specifically oriented towards novel compounds found in the course of biodiscovery. Here, we present a proof-of-concept by applying the novel method to a compound that has recently been isolated from a marine cyanobacteria due to its lipid-reducing activities [14]. The compound is a chlorophyll derivative, 13 2 -hydroxy-pheophytine a, which is present in marine and terrestrial organisms.…”

Section: Discussionmentioning

confidence: 99%

“…This is an improvement of the TPP method enabling sensitive analysis of protein targets across a proteome in any novel bioactive compound. To demonstrate the applicability of bTPP to the field of biodiscovery, we studied the protein targets of 13 2 -hydroxy-pheophytin a, a chlorophyll derivative with novel lipid-reducing activities that has recently been isolated from a marine cyanobacteria [14]. Given that this molecule is produced in high quantities in Spirulina , and is approved for human consumption, it is possible that a nutraceutical with anti-obesity activity may be developed in the future [14].…”

Section: Introductionmentioning

confidence: 99%

“…To demonstrate the applicability of bTPP to the field of biodiscovery, we studied the protein targets of 13 2 -hydroxy-pheophytin a, a chlorophyll derivative with novel lipid-reducing activities that has recently been isolated from a marine cyanobacteria [14]. Given that this molecule is produced in high quantities in Spirulina , and is approved for human consumption, it is possible that a nutraceutical with anti-obesity activity may be developed in the future [14]. The identification of the direct targets of 13 2 -hydroxy-pheophytin a (hpa) in HepG2 liver cells and the discussion of possible MOA will provide important information in terms of its applicability.…”

Section: Introductionmentioning

confidence: 99%

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Application of Bioactive Thermal Proteome Profiling to Decipher the Mechanism of Action of the Lipid Lowering 132-Hydroxy-pheophytin Isolated from a Marine Cyanobacteria

Amor

Freitas²,

Urbatzka³

et al. 2019

Marine Drugs

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The acceleration of the process of understanding the pharmacological application of new marine bioactive compounds requires identifying the compound protein targets leading the molecular mechanisms in a living cell. The thermal proteome profiling (TPP) methodology does not fulfill the requirements for its application to any bioactive compound lacking chemical and functional characterization. Here, we present a modified method that we called bTPP for bioactive thermal proteome profiling that guarantees target specificity from a soluble subproteome. We showed that the precipitation of the microsomal fraction before the thermal shift assay is crucial to accurately calculate the melting points of the protein targets. As a probe of concept, the protein targets of 132-hydroxy-pheophytin, a compound previously isolated from a marine cyanobacteria for its lipid reducing activity, were analyzed on the hepatic cell line HepG2. Our improved method identified 9 protein targets out of 2500 proteins, including 3 targets (isocitrate dehydrogenase, aldehyde dehydrogenase, phosphoserine aminotransferase) that could be related to obesity and diabetes, as they are involved in the regulation of insulin sensitivity and energy metabolism. This study demonstrated that the bTPP method can accelerate the field of biodiscovery, revealing protein targets involved in mechanisms of action (MOA) connected with future applications of bioactive compounds.

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“…In recent studies the use of zebrafish for the study of secondary metabolites with bioactivities relevant to various metabolic functions produced by marine cyanobacteria was observed and some substances with activities of significant reduction of lipids [48,49].…”

Section: Drug Screening and Treatmentmentioning

confidence: 99%

Zebrafish as an Experimental Model for the Study of Obesity

Virote¹,

Vianna²,

Murgas³

2020

Zebrafish in Biomedical Research

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Obesity is considered a silent global pandemic, with a steady increase in adults and children. It is a complex disease that involves the interaction of genetic and environmental factors and predisposes individuals to severe chronic complications such as various types of cancer, dyslipidemia, hyperglycemia, hypercholesterolemia, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis. To help elucidate the physiological mechanisms of this comorbidity in order to identify and develop effective treatments, the use of animal models is indispensable. Zebrafish is emerging as an important model for studying obesity and related metabolic diseases. In addition to being a small animal, with high genetic similarity when compared to humans and easy to handle, zebrafish also has the main well-conserved metabolism-related functions such as appetite regulation, insulin regulation, and lipid storage. Zebrafish is also suitable for the identification of new targets associated with the risk and treatment of obesity in humans. In this review, we highlight the studies that use zebrafish to study metabolic diseases demonstrating their important contribution in this area of research.

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Chlorophyll Derivatives from Marine Cyanobacteria with Lipid-Reducing Activities

Cited by 39 publications

References 56 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

Application of Bioactive Thermal Proteome Profiling to Decipher the Mechanism of Action of the Lipid Lowering 132-Hydroxy-pheophytin Isolated from a Marine Cyanobacteria

Zebrafish as an Experimental Model for the Study of Obesity

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