Modulation of Glial Responses by Furanocembranolides: Leptolide Diminishes Microglial Inflammation in Vitro and Ameliorates Gliosis In Vivo in a Mouse Model of Obesity and Insulin Resistance.

Neurodegenerative diseases are age-related disorders caused by progressive neuronal death in different regions of the nervous system. Neuroinflammation, modulated by glial cells, is a crucial event during the neurodegenerative process; consequently, there is an urgency to find new therapeutic products with anti-glioinflammatory properties. Five new furanocembranolides (1-5), along with leptolide, were isolated from two different extracts of Leptogorgia sp., and compound 6 was obtained from chemical transformation of leptolide. Their structures were determined based on spectroscopic evidence. These seven furanocembranolides were screened in vitro by measuring their ability to modulate interleukin-1ß (IL-1ß) production by microglial BV2 cells after LPS (lipopolysaccharide) stimulation. Leptolide and compounds 3, 4 and 6 exhibited clear anti-inflammatory effects on microglial cells, while compound 2 presented a pro-inflammatory outcome. The in vitro results prompted us to assess anti-glioinflammatory effects of leptolide in vivo in a high-fat diet-induced obese mouse model. Interestingly, leptolide treatment ameliorated both microgliosis and astrogliosis in this animal model. Taken together, our results reveal a promising direct biological effect of furanocembranolides on microglial cells as bioactive anti-inflammatory molecules. Among them, leptolide provides us a feasible therapeutic approach to treat neuroinflammation concomitant with metabolic impairment.

Chloro-Furanocembranolides from Leptogorgia sp. Improve Pancreatic Beta-Cell Proliferation.

Two new chloro-furanocembranolides (1, 2) and two new 1,4-diketo cembranolides (3, 4) were isolated from the crude extract of Leptogorgia sp. together with a new seco-furanocembranolide (5) and the known Z-deoxypukalide (6), rubifolide (7), scabrolide D (8) and epoxylophodione (9). Their structures were determined based on spectroscopic evidence. Four compounds: 1, 2, 7 and 8 were found to activate the proliferation of pancreatic insulin-producing (beta) cells.

[Environmental response in the Pacific to aseismic Cocos Ridge subduction (Panama and Costa Rica)]. / Respuesta ambiental en el pacífico frente a la subducción de la dorsal asísmica de Cocos (Panamá y Costa Rica).

The evolution of the marine communities along the Pacific coast of Central America, may have changed in response to the formation of the Isthmus of Panama. To evaluate the effect of the Aseismic Cocos Ridge (DAC) subduction on the marine benthic communities, we reconstructed benthic assemblages from Neogene fossiliferous formations in Burica and Nicoya peninsulas of Panama and Costa Rica. Paleoecological and paleoenvironmental conditions were reconstructed by comparing community structure from bulk fossil samples with dredge collections from modern Tropical American seas, using principal component analysis. Our results indicate that during the early Pliocene, before the closing of the Isthmus, some oceanic islands existed with moderate upwelling in the Burica region. After the closure, during the late Pliocene and early Pleistocene the collision of the DAC caused an uplift of the seafloor, where water depth of 2 300m became shallow waters of less than 40m depth. Meanwhile, upwelling intensified in the open ocean the uplift that had formed small islands in coastal areas of Burica, creating protected areas and limiting the upwelling effect that was given in open ocean. The subduction of the DAC continued until the islands were joined to the mainland and gradually disappeared, allowing the return of the upwelling. During the middle Pleistocene a second process of accelerated uplift with speeds of 8m/1000 years provoked again the elevation of the seafloor and later the elevation of the Talamanca Range. The new range formed a barrier that blocked the passage of the Trade winds, created new ecological conditions and optimized and allowed the growth of the best coral reefs in the coasts of the tropical Eastern Pacific (POT) between Panama and Costa Rica.

Carijodienone from the octocoral Carijoa multiflora. A spiropregnane-based steroid.

Two new steroids (1 and 2) and the known pregna-1,4,20-trien-3-one (3) have been isolated from the Pacific octocoral Carijoa multiflora. Compound 1 possesses a novel spiropregnane-based steroidal skeleton. The photochemical transformation of 3 into 1 allowed the assignment of the absolute configuration at C-10 of 1. The antibacterial activities of compounds 1 and 3 were evaluated against a panel of bacterial strains.

Validating an endoperoxide as a key intermediate in the biosynthesis of elysiapyrones.

Compounds 1-3 isolated from Elysia diomedea are described. Compound 1 is an endoperoxide derivative of elysiapyrone A. The biomimetic-type transformation of compound 1 to elysiapyrone A catalyzed by neutral base transformed the endoperoxide to a vicinal diepoxide, thus suggesting the endoperoxide as a key intermediate in the biosynthesis of elysiapyrone A. A biogenetic pathway for their formation involving a cycloaddition of singlet oxygen to a polypropionate alkenyl open chain is proposed.

Environmental change preceded Caribbean extinction by 2 million years.

Paleontologists typically treat major episodes of extinction as single and distinct events in which a major environmental perturbation results in a synchronous evolutionary response. Alternatively, the causes of biotic change may be multifaceted and extinction may lag behind the changes ultimately responsible because of nonlinear ecological dynamics. We examined these alternatives for the major episode of Caribbean extinction 2 million years ago (Ma). Isolation of the Caribbean from the Eastern Pacific by uplift of the Panamanian Isthmus was associated with synchronous changes in Caribbean near shore environments and community composition between 4.25 and 3.45 Ma. Seasonal fluctuations in Caribbean seawater temperature decreased 3-fold, carbonate deposition increased, and there was a striking, albeit patchy, shift in dominance of benthic ecosystems from heterotrophic mollusks to mixotrophic reef corals and calcareous algae. All of these changes correspond well with a simple model of decreased upwelling and collapse in planktonic productivity associated with the final stages of the closure of the isthmian barrier. However, extinction rates of mollusks and corals did not increase until 3-2 Ma and sharply peaked between 2 and 1 Ma, even though extinction overwhelmingly affected taxa commonly associated with high productivity. This time lag suggests that something other than environmental change per se was involved in extinction that does not occur as a single event. Understanding cause and effect will require more taxonomically refined analysis of the changing abundance and distribution patterns of different ecological guilds in the 2 million years leading up to the relatively sudden peak in extinction.

13C NMR-based empirical rules to determine the configuration of fatty acid butanolides. Novel gamma-dilactones from Pterogorgia spp.

Diastereomeric gamma-dilactones isolated from Pterogorgia spp allowed the establishment of (13)C NMR-based empirical rules to determine the relative stereochemistry of 3-alkyl-4-hydroxy-5-methyl-2(5H)-dihydrofuranones, gamma-lactone moieties ubiquitous in many bioactive synthetic and natural products. An NMR-based method using Pirkle's reagent at low temperature allowed the absolute configuration of the naturally occurring dibutenolides to be unambiguously determined. A biogenetic pathway that involves oxidation of long-chain (C16:0 and C18:0) fatty acids is proposed. [structure: see text]

Elysiapyrones from Elysia diomedea. Do such metabolites evidence an enzymatically assisted electrocyclization cascade for the biosynthesis of their bicyclo[4.2.0]octane core?

[structure: see text] Biogenetically interesting polypropionate-derived metabolites 1 and 2, featuring an unprecedented skeleton, have been isolated from the sea slug Elysia diomedea. Their enantiomeric character indicates that the current spontaneous electrocyclization cascade biogenetic hypothesis for the bicyclo[4.2.0]octane core must be enzymatically aided. These compounds are isomeric with the 15-nor-9,10-deoxytridachione/15-norphotodeoxytridachione pair of metabolites and encourage speculation about their biosynthetic relationship.

Carijenone, a novel class of bicyclic prostanoid from the eastern Pacific octocoral Carijoa multiflora.

[structure: see text] An unprecedented biogenetically interesting bicyclic prostanoid 1, carijenone, has been isolated from the eastern Pacific octocoral Carijoa multiflora. The C-12 oxygenated function, characteristic of the coral cyclopentanone fatty acid derivatives, is involved in the formation of a five-membered oxane ring fused to the cyclopentane network. Its structure and stereochemistry were determined on the basis of spectral studies and molecular mechanics calculations.