The Madeira Archipelago As a Significant Source of Marine-Derived Actinomycete Diversity with Anticancer and Antimicrobial Potential.

Marine-derived actinomycetes have demonstrated an ability to produce novel compounds with medically relevant biological activity. Studying the diversity and biogeographical patterns of marine actinomycetes offers an opportunity to identify genera that are under environmental pressures, which may drive adaptations that yield specific biosynthetic capabilities. The present study describes research efforts to explore regions of the Atlantic Ocean, specifically around the Madeira Archipelago, where knowledge of the indigenous actinomycete diversity is scarce. A total of 400 actinomycetes were isolated, sequenced, and screened for antimicrobial and anticancer activities. The three most abundant genera identified were Streptomyces, Actinomadura, and Micromonospora. Phylogenetic analyses of the marine OTUs isolated indicated that the Madeira Archipelago is a new source of actinomycetes adapted to life in the ocean. Phylogenetic differences between offshore (>100 m from shore) and nearshore (< 100 m from shore) populations illustrates the importance of sampling offshore in order to isolate new and diverse bacterial strains. Novel phylotypes from chemically rich marine actinomycete groups like MAR4 and the genus Salinispora were isolated. Anticancer and antimicrobial assays identified Streptomyces, Micromonospora, and Salinispora as the most biologically active genera. This study illustrates the importance of bioprospecting efforts at unexplored regions of the ocean to recover bacterial strains with the potential to produce novel and interesting chemistry.

p,p'-Methoxyl-diphenyl diselenide protects against amyloid-ß induced cytotoxicity in vitro and improves memory deficits in vivo.

Behavioral evidence suggests that the organoselenium compound p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)2] ameliorates memory and learning performance in rodents. Here, we investigated the molecular mechanism of (MeOPhSe)2 neuroprotection in cortical neurons exposed to amyloid-ß (Aß) peptide as well as in Aß-infused mice. For this purpose, primary cultures of rat cortical neurons were pre-incubated with 10 µM of (MeOPhSe)2 or vehicle, followed by exposure to 25 µM Aß fragment 25-35 or vehicle. Furthermore, the therapeutic effect of (MeOPhSe)2 (5 mg/kg, oral route, daily for 5 days) on memory deficits was evaluated in mice exposed to Aß fragment 25-35 (3 nmol/3 µl/per site, intracerebroventricular infusion). The results demonstrate that (MeOPhSe)2 prevented Aß-induced cell death in vitro, associated with inhibition of caspase-3 and -9 activities, poly (ADP-ribose) polymerase (PARP) cleavage and c-Jun N-terminal kinase (JNK) activation. Further, (MeOPhSe)2 rescued Aß-induced memory impairment in mice. In conclusion, (MeOPhSe)2 is neuroprotective in vitro and in vivo, suggesting that this organoselenium compound offers a potential treatment option for Alzheimer's disease.

p,p'-Methoxyl-diphenyl diselenide prevents neurodegeneration and glial cell activation induced by streptozotocin in rats.

The purpose of this study was to investigate possible molecular targets involved in the neuroprotective effect of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)2], using a streptozotocin (STZ)-induced sporadic dementia of Alzheimer's type rat model. Male Wistar rats were injected with STZ (1.0 mg/8 µl; 4 µl/ventricle). After 21 days of STZ injection, regular diet-fed rats were supplemented with 10 ppm of (MeOPhSe)2 during 30 days. At the end of this period, rats performed object recognition and step-down passive avoidance tasks. Apoptosis was assessed by TUNEL staining and active caspase-3. Glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and microtubule associated protein 2 were determined by immunofluorescence in rat hippocampus. The results demonstrate that the (MeOPhSe)2 dietary supplementation reversed STZ-induced memory impairment by enhancing memory in sham rats. (MeOPhSe)2 was also effective in reducing STZ-induced apoptosis and preserving dendrites and synapses. Moreover, (MeOPhSe)2 inhibited activation of microglia and astrogliosis induced by STZ in the rat hippocampus. We conclude that the (MeOPhSe)2 neuroprotective action is related to inhibition of apoptosis and suppression of inflammation.