TY - JOUR AB - Cyanobacteria have demonstrated their therapeutic potential for many human diseases. In this work, cyanobacterial extracts were screened for lipid reducing activity in zebrafish larvae and in fatty-acid-overloaded human hepatocytes, as well as for glucose uptake in human hepatocytes and ucp1 mRNA induction in murine brown adipocytes. A total of 39 cyanobacteria strains were grown and their biomass fractionated, resulting in 117 chemical fractions. Reduction of neutral lipids in zebrafish larvae was observed for 12 fractions and in the human hepatocyte steatosis cell model for five fractions. The induction of ucp1 expression in murine brown adipocytes was observed in six fractions, resulting in a total of 23 bioactive non-toxic fractions. All extracts were analyzed by untargeted UPLC-Q-TOF-MS mass spectrometry followed by multivariate statistical analysis to prioritize bioactive strains. The metabolite profiling led to the identification of two markers with lipid reducing activity in zebrafish larvae. Putative compound identification using mass spectrometry databases identified them as phosphatidic acid and aromatic polyketides derivatives—two compound classes, which were previously associated with effects on metabolic disorders. In summary, we have identified cyanobacterial strains with promising lipid reducing activity, whose bioactive compounds needs to be identified in the future. AU - Ribeiro, T.* AU - Jónsdóttir, K.* AU - Hernandez-Bautista, R. AU - Silva, N.G.* AU - Sánchez-Astráin, B.* AU - Samadi, A.* AU - Eiriksson, F.F.* AU - Thorsteinsdóttir, M.* AU - Ussar, S. AU - Urbatzka, R.* C1 - 68231 C2 - 54835 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Metabolite profile characterization of cyanobacterial strains with bioactivity on lipid metabolism using in vivo and in vitro approaches. JO - Mar. Drugs VL - 21 IS - 9 PB - Mdpi PY - 2023 SN - 1660-3397 ER - TY - JOUR AB - Obesity is a complex disease resulting in several metabolic co-morbidities and is increasing at epidemic rates. The marine environment is an interesting resource of novel compounds and in particular cyanobacteria are well known for their capacity to produce novel secondary metabolites. In this work, we explored the potential of cyanobacteria for the production of compounds with relevant activities towards metabolic diseases using a blend of target-based, phenotypic and zebrafish assays as whole small animal models. A total of 46 cyanobacterial strains were grown and biomass fractionated, yielding in total 263 fractions. Bioactivities related to metabolic function were tested in different in vitro and in vivo models. Studying adipogenic and thermogenic gene expression in brown adipocytes, lipid metabolism and glucose uptake in hepatocytes, as well as lipid metabolism in zebrafish larvae, we identified 66 (25%) active fractions. This together with metabolite profiling and the evaluation of toxicity allowed the identification of 18 (7%) fractions with promising bioactivity towards different aspects of metabolic disease. Among those, we identified several known compounds, such as eryloside T, leptosin F, pheophorbide A, phaeophytin A, chlorophyll A, present as minor peaks. Those compounds were previously not described to have bioactivities in metabolic regulation, and both known or unknown compounds could be responsible for such effects. In summary, we find that cyanobacteria hold a huge repertoire of molecules with specific bioactivities towards metabolic diseases, which needs to be explored in the future. AU - Costa, M.* AU - Rosa, F.* AU - Ribeiro, T.* AU - Hernandez-Bautista, R. AU - Bonaldo, M.* AU - Gonçalves Silva, N.* AU - Eiríksson, F.* AU - Thorsteinsdóttir, M.* AU - Ussar, S. AU - Urbatzka, R.* C1 - 56057 C2 - 46784 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Identification of cyanobacterial strains with potential for the treatment of obesity-related co- morbidities by bioactivity, toxicity evaluation and metabolite profiling. JO - Mar. Drugs VL - 17 IS - 5 PB - Mdpi PY - 2019 SN - 1660-3397 ER - TY - JOUR AB - Marine algae represent an important source of novel natural products. While their bioactive potential has been studied to some extent, limited information is available on marine algae from the Red Sea. This study aimed at the broad discovery of new bioactivities from a collection of twelve macroalgal species from the Central Red Sea. We used imaging-based High-Content Screening (HCS) with a diverse spectrum of cellular markers for detailed cytological profiling of fractionated algal extracts. The cytological profiles for 3 out of 60 algal fractions clustered closely to reference inhibitors and showed strong inhibitory activities on the HIV-1 reverse transcriptase in a single-enzyme biochemical assay, validating the suggested biological target. Subsequent chemical profiling of the active fractions of two brown algal species by ultra-high resolution mass spectrometry (FT-ICR-MS) revealed possible candidate molecules. A database query of these molecules led us to groups of compounds with structural similarities, which are suggested to be responsible for the observed activity. Our work demonstrates the versatility and power of cytological profiling for the bioprospecting of unknown biological resources and highlights Red Sea algae as a source of bioactives that may serve as a starting point for further studies. AU - Kremb, S.* AU - Müller, C. AU - Schmitt-Kopplin, P. AU - Voolstra, C.R.* C1 - 50791 C2 - 42812 CY - Basel TI - Bioactive potential of marine macroalgae from the central red sea (Saudi Arabia) assessed by high-throughput imaging-based phenotypic profiling. JO - Mar. Drugs VL - 15 IS - 3 PB - Mdpi Ag PY - 2017 SN - 1660-3397 ER - TY - JOUR AB - The sponge Stylissa carteri is known to produce a number of secondary metabolites displaying anti-fouling, anti-inflammatory, and anti-cancer activity. However, the anti-viral potential of metabolites produced by S. carteri has not been extensively explored. In this study, an S. carteri extract was HPLC fractionated and a cell based assay was used to evaluate the effects of HPLC fractions on parameters of Human Immunodeficiency Virus (HIV-1) infection and cell viability. Candidate HIV-1 inhibitory fractions were then analyzed for the presence of potential HIV-1 inhibitory compounds by mass spectrometry, leading to the identification of three previously characterized compounds, i.e., debromohymenialdisine (DBH), hymenialdisine (HD), and oroidin. Commercially available purified versions of these molecules were re-tested to assess their antiviral potential in greater detail. Specifically, DBH and HD exhibit a 30%-40% inhibition of HIV-1 at 3.1 μM and 13 μM, respectively; however, both exhibited cytotoxicity. Conversely, oroidin displayed a 50% inhibition of viral replication at 50 μM with no associated toxicity. Additional experimentation using a biochemical assay revealed that oroidin inhibited the activity of the HIV-1 Reverse Transcriptase up to 90% at 25 μM. Taken together, the chemical search space was narrowed and previously isolated compounds with an unexplored anti-viral potential were found. Our results support exploration of marine natural products for anti-viral drug discovery. AU - O'Rourke, A.* AU - Kremb, S.* AU - Bader, T.M. AU - Helfer, M. AU - Schmitt-Kopplin, P. AU - Gerwick, W.H.* AU - Brack-Werner, R. AU - Voolstra, C.R.* C1 - 47882 C2 - 39696 CY - Basel TI - Alkaloids from the sponge Stylissa carteri present prospective scaffolds for the inhibition of Human Immunodeficiency Virus 1 (HIV-1). JO - Mar. Drugs VL - 14 IS - 2 PB - Mdpi Ag PY - 2016 SN - 1660-3397 ER - TY - JOUR AB - The majority of the marine algal species, though completing their life cycle in seawater, are rarely susceptible to fouling, making them an important source of quorum sensing (QS) inhibitory substances. The separation and characterization of QS inhibitors are crucial for any potential application. Thirty marine macroalgae were tested for QS inhibition activity by using Chromobacterium violaceum CV026 as the reporter strain, and among them, Asparagopsis taxiformis showed antibacterial, as well as antiquorum, sensing activities. Cinnamaldehyde (75 mM) and methanol were used as positive and negative controls, respectively. The antiquorum sensing activity of A. taxiformis was further confirmed using the sensor strain, Serratia liquefaciens MG44, having green fluorescent protein (gfp). Methanolic extract of the alga was fractionated by solid phase extraction (SPE), and each fraction was tested for QS inhibition. Two types of activities were observed-zone of clearance (antibacterial activity) and zone of inhibition with or without finger-like projections (QS inhibition). Out of five SPE cartridges, Bond Elut PH showed clear separation of these two fractions. The Ion Cyclotron Resonance Fourier Transformation Mass Spectrometer (ICR-FT/MS) analysis of the fractions further supported the bioassay results. The presence of strong QS inhibitory compound in A. taxiformis indicates its potential use in antifouling preparations. AU - Jha, B.* AU - Kavita, K.* AU - Westphal, J. AU - Hartmann, A. AU - Schmitt-Kopplin, P. C1 - 22553 C2 - 30910 SP - 253-265 TI - Quorum sensing inhibition by Asparagopsis taxiformis, a marine macro alga: Separation of the compound that interrupts bacterial communication. JO - Mar. Drugs VL - 11 IS - 1 PB - MDPI AG PY - 2013 SN - 1660-3397 ER -