1H NMR Spectroscopy and MVA Analysis of Diplodus sargus Eating the Exotic Pest Caulerpa cylindracea

6noThe green alga Caulerpa cylindracea is a non-autochthonous and invasive species that is severely affecting the native communities in the Mediterranean Sea. Recent researches show that the native edible fish Diplodus sargus actively feeds on this alga and cellular and physiological alterations have been related to the novel alimentary habits. The complex effects of such a trophic exposure to the invasive pest are still poorly understood. Here we report on the metabolic profiles of plasma from D. sargus individuals exposed to C. cylindracea along the southern Italian coast, using 1H NMR spectroscopy and multivariate analysis (Principal Component Analysis, PCA, Orthogonal Partial Least Square, PLS, and Orthogonal Partial Least Square Discriminant Analysis, OPLS-DA). Fish were sampled in two seasonal periods from three different locations, each characterized by a different degree of algal abundance. The levels of the algal bisindole alkaloid caulerpin, which is accumulated in the fish tissues, was used as an indicator of the trophic exposure to the seaweed and related to the plasma metabolic profiles. The profiles appeared clearly influenced by the sampling period beside the content of caulerpin, while the analyses also supported a moderate alteration of lipid and choline metabolism related to the Caulerpa-based diet.openopenS. A. De Pascali; L. Del Coco; S. Felline; E. Mollo; A. Terlizzi; F. P. FanizziS. A., De Pascali; L., Del Coco; S., Felline; E., Mollo; Terlizzi, Antonio; F. P., Fanizz

Natural Products from Marine Heterobranchs: an Overview of Recent Results

Heterobranchs are a fascinating group of marine mollusks that are recognized as an important source of bioactive natural products. Often, these molecules, which are either selected from the diet or de novo biosynthesized by the mollusks, play a fundamental role for their survival being utilized as defensive chemicals against predators. A summary of the studies carried out by our group, in the last decade, on heterobranchs is presented here. A number of new compounds exhibiting different molecular architectures have been chemically characterized. Some of them have also shown an interesting pharmacological potential. Some ecological studies that we conducted on selected species of heterobranchs are also reviewed

Cytosporin-related compounds from the marine-derived fungus Eutypella scoparia

[EN] Chemical investigation of the culture broth of the fungus Eutypella scoparia ICB-OBX, isolated from the marine pulmonate mollusc Onchidium sp., led to the finding of novel compounds 1 and 2, structurally related to angiotensin II binding inhibitors cytosporins, along with unrelated known nitrogen metabolites (compounds 3¿5). The structure and the relative stereochemistry of the novel metabolites were assigned mainly by a detailed analysis of two-dimensional NMR techniques whereas the absolute stereochemistry was proposed by modified Mosher's method. Compound 2 contains an unusual cyclic carbonate functionality that is rare among natural products.Ciavatta, ML.; López-Gresa, MP.; Gavagnin, M.; Nicoletti, R.; Manzo, E.; Mollo, E.; Guo, Y.... (2008). Cytosporin-related compounds from the marine-derived fungus Eutypella scoparia. Tetrahedron. 64(22):5365-5369. https://doi.org/10.1016/j.tet.2008.03.016S53655369642

Chemoecological studies on marine natural products: terpene chemistry from marine mollusks

Some species of nudibranchs (Mollusca) protect themselves from predatory attacks by storing defensive terpene chemicals acquired from dietary sponges (Porifera) in specialized body parts called MDFs (mantle dermal formations), often advertising their unpalatability to potential predators by means of bright coloration patterns. Consequently, the survival of these trophic specialist species is closely related to the possibility of obtaining the defensive tools from sponges that live in their immediate vicinity; therefore, it is important to determine as precisely as possible the chemical composition of nudibranch extracts prior to any ecological studies addressing issues that involve their alimentary behavior and their defensive strategies, including the significance of their color patterns. Some of our recent studies on the chemical composition of terpene extracts from nudibranchs belonging to the genera Chromodoris and Hypselodoris are summarized. We also report the development of a method to assay extracts and purified metabolites for their feeding deterrent activity against co-occurring generalist predators. In a recent chemoecological study, showing that repugnant terpene chemicals are accumulated at extremely high concentrations in exposed parts of the nudibranchs' bodies, the feeding deterrence assays were carried out on the generalist marine shrimp Palaemon elegans, very common in the Mediterranean. We have modified this assay for use with the Australian shrimp species P. serenus, and confirmed the ecological validity of the assay by analysis of extracts from species of sponges and mollusks that live in the same habitat as P. serenus. The deterrent properties of haliclonacyclamine alkaloids isolated from the sponge Haliclona sp. were demonstrated, with the alkaloid mixture demonstrating palatability deterrence at concentrations as low as 0.05 mg/mL, and complete deterrence at 0.75 mg/mL. In contrast, the diterpene thuridillin metabolites from the sacoglossan mollusk Thuridilla splendens did not deter feeding by P. serenus

An alien metabolite vs. a synthetic chemical hazard: an ecotoxicological comparison in the Mediterranean blue mussel

Bioactive natural products from marine invasive species may dramatically impact native communities, while many synthetic pharmaceutical drugs are released into the marine environment and have long-lasting harmful effects on aquatic life. Sometimes, metabolites from alien species and synthetic compounds share similar mechanisms of action, suggesting comparable ecotoxicological impacts. This applies to the alkaloid caulerpin (CAU) from the green alga Caulerpa cylindracea, highly invasive in the Mediterranean Sea, and to the synthetic lipid-lowering drug fenofibrate (FFB), both acting as agonists of peroxisome proliferator-activated receptors (PPARs). Analogies with FFB, which is widely considered hazardous to the aquatic environment, have led to concerns about the ecotoxicological potential of CAU. The problem has implications for public health as CAU is well known to enter the food web accumulating in fish of commercial importance. Here, we compared the effects of FFB and CAU through biochemical and histopathological analysis on a relevant bioindicator molluscan species, the mussel Mytilus galloprovincialis. Under laboratory conditions, mussels were fed with food enriched with CAU or FFB. After treatment, biochemical markers were analyzed revealing metabolic capacity impairments, cellular damage, and changes in acetylcholinesterase activity in mussels fed with FFB-enriched food. NMR-based metabolomic studies also showed significant alterations in the metabolic profiles of FFB-treated mussels. In addition, dietary administration of FFB produced morphological alterations in the mussels' gills and digestive tubules. Obtained results confirm that FFB is harmful to aquatic life and that its release into the environment should be avoided. Conversely, dietary treatment with CAU did not produce any significant alterations in the mussels. Overall, our results pave the way for the possible valorization of the huge biomass from one of the world's worst invasive species to obtain CAU, a natural product of interest in drug discovery.publishe

An Alkaloid from a Highly Invasive Seaweed Increases the Voracity and Reproductive Output of a Model Fish Species

The invasive macroalga Caulerpa cylindracea has spread widely in the Mediterranean Sea, becoming a favorite food item for native fish for reasons yet unknown. By using a combination of behavioral, morphological, and molecular approaches, herein we provide evidence that the bisindole alkaloid caulerpin, a major secondary metabolite of C. cylindracea, significantly increases food intake in the model fish Danio rerio, influencing the regulation of genes involved in the orexigenic pathway. In addition, we found that the compound improves fish reproductive performance by affecting the hypothalamus-pituitary-gonadal axis. The obtained results pave the way for the possible valorization of C. cylindracea as a sustainable source of a functional feed additive of interest to face critical challenges both in aquaculture and in human nutrition

Taste and Smell: A Unifying Chemosensory Theory

Since antiquity, the sense of smell (olfaction) is considered as a distance sense, just like sight and hearing. Conversely, the sense of taste (gustation) is thought to operate by direct contact, similarly to touch. With the progress of natural sciences, information at molecular, anatomical, and neurobiological levels has also contributed to the taste-smell dichotomy, but much evidence inconsistent with a sharp differentiation of these two senses has emerged, especially when considering species other than humans. In spite of this, conflicting information has been interpreted so that it could conform to the traditional differentiation. As a result, a confirmation bias is currently affecting scientific research on chemosensory systems and is also hindering the development of a satisfactory narrative of the evolution of chemical communication across taxa. From this perspective, the chemosensory dichotomy loses its validity and usefulness. We thus propose the unification of all chemosensory modalities into a single sense, moving toward a synthetic, complex, and interconnected perspective on the gradual processes by which a vast variety of chemicals have become signals that are crucially important to communication among and within cells, organs, and organisms in a wide variety of environmental condition

Taste and Smell: A Unifying Chemosensory Theory

Since antiquity, the sense of smell (olfaction) is considered as a distance sense, just like sight and hear- ing. Conversely, the sense of taste (gustation) is thought to operate by direct contact, similarly to touch. With the progress of natural sciences, information at molecular, anatomical, and neurobiological levels has also contributed to the taste-smell dichotomy, but much evidence inconsistent with a sharp differenti- ation of these two senses has emerged, especially when considering species other than humans. In spite of this, conflicting information has been interpreted so that it could conform to the traditional differentia- tion. As a result, a confirmation bias is currently affecting scientific research on chemosensory systems and is also hindering the development of a satisfactory narrative of the evolution of chemical communi- cation across taxa. From this perspective, the chemosensory dichotomy loses its validity and usefulness. We thus propose the unification of all chemosensory modalities into a single sense, moving toward a synthetic, complex, and interconnected perspective on the gradual processes by which a vast variety of chemicals have become signals that are crucially important to communication among and within cells, organs, and or- ganisms in a wide variety of environmental conditions

Fishing for Targets of Alien Metabolites: A Novel Peroxisome Proliferator-Activated Receptor (PPAR) Agonist from a Marine Pest

Although the chemical warfare between invasive and native species has become a central problem in invasion biology, the molecular mechanisms by which bioactive metabolites from invasive pests influence local communities remain poorly characterized. This study demonstrates that the alkaloid caulerpin (CAU)—a bioactive component of the green alga Caulerpa cylindracea that has invaded the entire Mediterranean basin—is an agonist of peroxisome proliferator-activated receptors (PPARs). Our interdisciplinary study started with the in silico prediction of the ligand-protein interaction, which was then validated by in vivo, ex vivo and in vitro assays. On the basis of these results, we candidate CAU as a causal factor of the metabolic and behavioural disorders observed in Diplodus sargus, a native edible fish of high ecological and commercial relevance, feeding on C. cylindracea. Moreover, given the considerable interest in PPAR activators for the treatment of relevant human diseases, our findings are also discussed in terms of a possible nutraceutical/pharmacological valorisation of the invasive algal biomasses, supporting an innovative strategy for conserving biodiversity as an alternative to unrealistic campaigns for the eradication of invasive pest

New caulerpenyne-derived metabolites of an Elysia sacoglossan from the south indian coast

[EN] Chemical analysis of the secondary metabolite pattern of the sacoglossan mollusc Elysia cf. expansa, collected along South Indian coasts, showed the presence of the typical Caulerpa-derived sesquiterpene caulerpenyne (1) and two new minor co-occurring metabolites, the compounds dihydrocaulerpenyne (4) and expansinol (5). The chemical characterization of these molecules, structurally related to 1, is reported.We thank ICB Mass Service and ICB NMR Service Centre (Mrs. D. Melck is kindly acknowledged), Mr. C. Iodice for spectrophotometric measurements and Mr. R. Turco for graphical work. This work was partially supported by a bilateral CNR-CSIR project.Ciavatta, ML.; López-Gresa, MP.; Gavagnin, M.; Manzo, E.; Mollo, E.; D Souza, L.; Cimino, G. (2006). New caulerpenyne-derived metabolites of an Elysia sacoglossan from the south indian coast. Molecules. 11(10):808-816. doi:10.3390/11100808S808816111