The Protective Role of Oleuropein Aglycone against Pesticide-Induced Toxicity in a Human Keratinocytes Cell Model.

The extensive use of agricultural pesticides to improve crop quality and yield significantly increased the risk to the public of exposure to small but repeated doses of pesticides over time through various routes, including skin, by increasing the risk of disease outbreaks. Although much work was conducted to reduce the use of pesticides in agriculture, little attention was paid to prevention, which could reduce the toxicity of pesticide exposure by reducing its impact on human health. Extra virgin olive oil (EVOO), a major component of the Mediterranean diet, exerts numerous health-promoting properties, many of which are attributed to oleuropein aglycone (OleA), the deglycosylated form of oleuropein, which is the main polyphenolic component of EVOO. In this work, three pesticides with different physicochemical and biological properties, namely oxadiazon (OXA), imidacloprid (IMID), and glyphosate (GLYPHO), were compared in terms of metabolic activity, mitochondrial function and epigenetic modulation in an in vitro cellular model of human HaCaT keratinocytes to mimic the pathway of dermal exposure. The potential protective effect of OleA against pesticide-induced cellular toxicity was then evaluated in a cell pre-treatment condition. This study showed that sub-lethal doses of OXA and IMID reduced the metabolic activity and mitochondrial functionality of HaCaT cells by inducing oxidative stress and altering intracellular calcium flux and caused epigenetic modification by reducing histone acetylation H3 and H4. GLYPHO, on the other hand, showed no evidence of cellular toxicity at the doses tested. Pretreatment of cells with OleA was able to protect cells from the damaging effects of the pesticides OXA and IMID by maintaining metabolic activity and mitochondrial function at a controlled level and preventing acetylation reduction, particularly of histone H3. In conclusion, the bioactive properties of OleA reported here could be of great pharmaceutical and health interest, as they could be further studied to design new formulations for the prevention of toxicity from exposure to pesticide use.

Ameliorative Effect of Posidonia oceanica on High Glucose-Related Stress in Human Hepatoma HepG2 Cells.

Metabolic disorders characterized by elevated blood glucose levels are a recognized risk factor for hepatocellular carcinoma (HCC). Lipid dysregulation is critically involved in the HCC progression, regulating energy storage, metabolism, and cell signaling. There is a clear link between de novo lipogenesis in the liver and activation of the NF-κB pathway, which is involved in cancer metastasis via regulation of metalloproteinases MMP-2/9. As conventional therapies for HCC reach their limits, new effective and safe drugs need to be found for the prevention and/or adjuvant therapy of HCC. The marine plant Posidonia oceanica (L.) Delile is endemic to the Mediterranean and has traditionally been used to treat diabetes and other health disorders. The phenol-rich leaf extract of Posidonia oceanica (POE) is known to have cell-safe bioactivities. Here, high glucose (HG) conditions were used to study lipid accumulation and fatty acid synthase (FASN) expression in human HepG2 hepatoma cells using Oil Red O and Western blot assays. Under HG conditions, the activation status of MAPKs/NF-κB axis and MMP-2/9 activity were determined by Western blot and gelatin zymography assays. The potential ameliorative role of POE against HG-related stress in HepG2 cells was then investigated. POE reduced lipid accumulation and FASN expression with an impact on de novo lipogenesis. Moreover, POE inhibited the MAPKs/NF-κB axis and, consequently, MMP-2/9 activity. Overall, these results suggest that P. oceanica may be a potential weapon in the HCC additional treatment.

Neutrophil Gelatinase-Associated Lipocalin as Potential Predictive Biomarker of Melanoma and Non-Melanoma Skin Cancers in Psoriatic Patients: A Pilot Study.

Background: Studies have demonstrated a higher risk of nonmelanoma skin cancers (NMSC) and a modestly increased melanoma risk in patients with psoriasis. To date, no biomarkers predictive of evolution have been identified yet. Methods: The aim of this prospective case-control study was to investigate the potential role of neutrophil gelatinase-associated lipocalin (NGAL) as a predictive biomarker of skin cancers in psoriatic patients. Patients with a diagnosis of psoriasis were enrolled, as well as healthy subjects and patients with skin cancers as controls. Plasma protein expression of NGAL, metalloproteinases (MMP)-2, and MMP-9 was performed by an enzyme-linked immunosorbent assay (ELISA). In all the patients who developed skin cancer at follow-up, NGAL, MMP-2, and MMP-9 serum levels were dosed again. Results: Plasma NGAL levels were significantly higher in psoriatic patients with NMSC than without (182.3 ± 36.6 ng/mL vs. 139.9 ± 39.3 ng/mL) (p < 0.001). Plasma NGAL levels were significantly higher (p < 0.00001) in patients with psoriasis and NMSC than in patients with skin tumors without psoriasis (182.3 vs. 122.9). Patients with psoriasis who developed NMSC at follow-up showed increased plasma MMP-9 levels. Conclusion: NGAL seems to play a role in the pathogenesis of NMSC but not melanoma in patients with psoriasis.

Marine Migrastatics: A Comprehensive 2022 Update.

Metastasis is responsible for the bad prognosis in cancer patients. Advances in research on metastasis prevention focus attention on the molecular mechanisms underlying cancer cell motility and invasion to improve therapies for long-term survival in cancer patients. The so-called "migrastatics" could help block cancer cell invasion and lead to the rapid development of antimetastatic therapies, improving conventional cancer therapies. In the relentless search for migrastatics, the marine environment represents an important source of natural compounds due to its enormous biodiversity. Thus, this review is a selection of scientific research that has pointed out in a broad spectrum of in vitro and in vivo models the anti-cancer power of marine-derived products against cancer cell migration and invasion over the past five years. Overall, this review might provide a useful up-to-date guide about marine-derived compounds with potential interest for pharmaceutical and scientific research on antimetastatic drug endpoints.

Dihydroauroglaucin Isolated from the Mediterranean Sponge Grantia compressa Endophyte Marine Fungus Eurotium chevalieri Inhibits Migration of Human Neuroblastoma Cells.

Cancer cell migration is a hallmark of the aggressiveness and progression of malignancies such as high-risk neuroblastoma. Given the lack of effective therapeutic solutions to counteract cancer progression, basic research aims to identify novel bioactive molecules with inhibitory potential on cancer cell migration. In this context, this work investigated the role of members of the salicylaldehyde secondary metabolite set from the sponge endophyte fungus Eurotium chevalieri MUT 2316 as potential inhibitors of human neuroblastoma SH-SY5Y cell migration. Since tetrahydroauroglaucin (TAG) and dihydroauroglaucin (DAG) were isolated in large amounts, both were evaluated for their anticancer properties towards SH-SY5Y cells. Both molecules were found to be non-cytotoxic by MTT assay and cytofluorimetric analysis. Moreover, DAG showed efficacy in inhibiting the highly migratory phenotype of SH-SY5Y cells by wound healing assay; whereas TAG, although structurally similar to DAG, showed no anti-migratory effect. Therefore, this work provides good reasons to conduct further in vitro and in vivo studies focusing on DAG as a potentially useful migrastatic natural marine molecule.

Posidonia oceanica (L.) Delile Extract Reduces Lipid Accumulation through Autophagy Activation in HepG2 Cells.

Posidonia oceanica (L.) Delile is a marine plant traditionally used as an herbal medicine for various health disorders. P. oceanica leaf extract (POE) has been shown to be a phytocomplex with cell-safe bioactivities, including the ability to trigger autophagy. Autophagy is a key pathway to counteract non-alcoholic fatty liver disease (NAFLD) by controlling the breakdown of lipid droplets in the liver. The aim of this study was to explore the ability of POE to trigger autophagy and reduce lipid accumulation in human hepatoma (HepG2) cells and then verify the possible link between the effect of POE on lipid reduction and autophagy activation. Expression levels of autophagy markers were monitored by the Western blot technique in POE-treated HepG2 cells, whereas the extent of lipid accumulation in HepG2 cells was assessed by Oil red O staining. Chloroquine (CQ), an autophagy inhibitor, was used to study the relationship between POE-induced autophagy and intracellular lipid accumulation. POE was found to stimulate an autophagy flux over time in HepG2 cells by lowering the phosphorylation state of ribosomal protein S6, increasing Beclin-1 and LC3-II levels, and decreasing p62 levels. By blocking autophagy with CQ, the effect of POE on intracellular lipid accumulation was clearly reversed, suggesting that the POE phytocomplex may reduce lipid accumulation in HepG2 cells by activating the autophagic process. This work indicates that P. oceanica may be considered as a promising molecule supplier to discover new natural approaches for the management of NAFLD.

Posidonia oceanica (L.) Delile Dampens Cell Migration of Human Neuroblastoma Cells.

Neuroblastoma (NB) is a common cancer in childhood, and lethal in its high-risk form, primarily because of its high metastatic potential. Targeting cancer cell migration, and thus preventing metastasis formation, is the rationale for more effective cancer therapy against NB. Previous studies have described the leaf extract from Posidonia oceanica marine plant (POE) as an antioxidant, anti-inflammatory agent and inhibitor of cancer cell migration. This study aims to examine the POE anti-migratory role in human SH-SY5Y neuroblastoma cells and the underlying mechanisms of action. Wound healing and gelatin zymography assays showed that POE at early times inhibits cell migration and reduces pro-MMP-2 release into culture medium. By monitoring expression level of key autophagy markers by Western blot assay, a correlation between POE-induced cell migration inhibition and autophagy activation was demonstrated. Cell morphology and immunofluorescence analyses showed that POE induces neurite formation and neuronal differentiation at later times. These results suggest POE might act against cell migration by triggering early nontoxic autophagy. The POE-induced cellular morphological change toward cell differentiation might contribute to prolonging the phytocomplex anti-migratory effect to later times. Overall, these results encourage future in vivo studies to test POE applicability in neuroblastoma treatment.

An Overview of New Insights into the Benefits of the Seagrass Posidonia oceanica for Human Health.

Posidonia oceanica (L.) Delile is a Mediterranean-endemic angiosperm often described for its great ecological importance. Despite evidence of a millennia-old relationship between P. oceanica and humans, as well as traditional medicine applications, the potential benefits of P. oceanica for human health have been documented only recently. This review aims to compile newly acquired knowledge on P. oceanica bioactive properties that allow the scientific community to look at this plant as a promising source of natural therapeutical products for human health. Experimental investigations conducted in both in vitro cellular-based and in vivo animal models pave the way for new research projects aiming at the development of alternative and complementary therapeutic strategies based on P. oceanica against a wide range of pathological conditions.

Efficacy of Posidonia oceanica Extract against Inflammatory Pain: In Vivo Studies in Mice.

Posidonia oceanica (L.) Delile is traditionally used for its beneficial properties. Recently, promising antioxidant and anti-inflammatory biological properties emerged through studying the in vitro activity of the ethanolic leaves extract (POE). The present study aims to investigate the anti-inflammatory and analgesic role of POE in mice. Inflammatory pain was modeled in CD-1 mice by the intraplantar injection of carrageenan, interleukin IL-1ß and formalin. Pain threshold was measured by von Frey and paw pressure tests. Nociceptive pain was studied by the hot-plate test. POE (10-100 mg kg-1) was administered per os. The paw soft tissue of carrageenan-treated animals was analyzed to measure anti-inflammatory and antioxidant effects. POE exerted a dose-dependent, acute anti-inflammatory effect able to counteract carrageenan-induced pain and paw oedema. Similar anti-hyperalgesic and anti-allodynic results were obtained when inflammation was induced by IL-1ß. In the formalin test, the pre-treatment with POE significantly reduced the nocifensive behavior. Moreover, POE was able to evoke an analgesic effect in naïve animals. Ex vivo, POE reduced the myeloperoxidase activity as well as TNF-α and IL-1ß levels; further antioxidant properties were highlighted as a reduction in NO concentration. POE is the candidate for a new valid strategy against inflammation and pain.

Thymoquinone-Loaded Soluplus®-Solutol® HS15 Mixed Micelles: Preparation, In Vitro Characterization, and Effect on the SH-SY5Y Cell Migration.

Thymoquinone (TQ) is the main active ingredient of Nigella sativa essential oil, with remarkable anti-neoplastic activities with anti-invasive and anti-migratory abilities on a variety of cancer cell lines. However, its poor water solubility, high instability in aqueous solution and pharmacokinetic drawbacks limits its use in therapy. Soluplus® and Solutol® HS15 were employed as amphiphilic polymers for developing polymeric micelles (SSM). Chemical and physical characterization studies of micelles are reported, in terms of size, homogeneity, zeta potential, critical micelle concentration (CMC), cloud point, encapsulation efficiency (EE%), load capacity (DL), in vitro release, and stability. This study reports for the first time the anti-migratory activity of TQ and TQ loaded in SSM (TQ-SSM) in the SH-SY5Y human neuroblastoma cell line. The inhibitory effect was assessed by the wound-healing assay and compared with that of the unformulated TQ. The optimal TQ-SSM were provided with small size (56.71 ± 1.41 nm) and spherical shape at ratio of 1:4 (Soluplus:Solutol HS15), thus increasing the solubility of about 10-fold in water. The entrapment efficiency and drug loading were 92.4 ± 1.6% and 4.68 ± 0.12, respectively, and the colloidal dispersion are stable during storage for a period of 40 days. The TQ-SSM were also lyophilized to obtain a more workable product and with increased stability. In vitro release study indicated a prolonged release of TQ. In conclusion, the formulation of TQ into SSM allows a bio-enhancement of TQ anti-migration activity, suggesting that TQ-SSM is a better candidate than unformulated TQ to inhibit human SH-SY5Y neuroblastoma cell migration.

Annona cherimola Miller Fruit as a Promising Candidate against Diabetic Complications: An In Vitro Study and Preliminary Clinical Results.

Diabetes is a chronic metabolic disease with a strong social impact worldwide. Under chronic hyperglycemia, protein glycation strongly contributes to diabetes-related complications onset. Anti-glycation agents and inhibitors of α-glucosidase are often therapeutically used to control postprandial glycemia in order to prevent development of long-term diabetic complications. Given drug resistance and adverse effects of conventional antidiabetic therapies, the discovery of new effective and non-toxic naturally occurring compounds is needed to prevent and/or to manage life-threatening diabetic complications. Annona cherimola Miller fruit has been used in Mexican traditional medicine as natural remedy against diabetes. In this work, the in vitro anti-glycation and anti-α-glucosidase roles of Annona cherimola Miller pulp extract (CE) were investigated. Moreover, healthy and diabetic subjects were enrolled in a cross-over design intervention study aimed at investigating the effects of pulp intake on postprandial glycemia. This work shows that CE was able to inhibit albumin glycation in vitro and to inhibit α-glucosidase enzyme. Furthermore, the pulp intake did not contribute to an increase in postprandial glycemia, making it a suitable source of health-promoting phytonutrients and a potential functional food in diabetics and pre-diabetics diet.

The In Vitro Anti-amyloidogenic Activity of the Mediterranean Red Seaweed Halopithys Incurva.

Neurodegenerative diseases are generally characterized by the presence of neurotoxic amyloid aggregates underlying progressive neuronal death. Since ancient times, natural compounds have been used as curative agents for human health. Amyloid research is constantly looking for safe natural molecules capable of blocking toxic amyloid aggregates' formation. From the marine environment, seaweeds are recognized as rich reservoirs of molecules with multiple bioactivities, including the anti-amyloidogenic activity. Here, hydroalcoholic extracts of two seasonal samples of the Mediterranean red seaweed Halophytis incurva (HIEs) were characterized by the HPLC-DAD-MS analysis. The H. incurva anti-amyloidogenic role was explored by incubating both HIEs with hen egg white lysozyme (HEWL), a well-known protein model widely used in amyloid aggregation experiments. The aggregation kinetics and morphological analysis of amyloid aggregates were performed by ThT and AFM analysis, respectively, while their cytotoxicity on SH-SY5Y human neuroblastoma cells was examined by MTT assay. HIEs showed a different efficacy, probably dependent on their metabolic composition, both in inhibiting amyloid fibrillation and in obtaining short and less toxic pre-fibrillary aggregates. Overall, this work sheds light, for the first time, on a Mediterranean red seaweed as a promising renewable resource of bioactive compounds, potentially useful in preventing the formation of toxic amyloid aggregates.

Maysin plays a protective role against α-Synuclein oligomers cytotoxicity by triggering autophagy activation.

Parkinson's disease (PD) is a widespread neurodegenerative disorder characterized by the progressive loss of neurons. The accumulation of aggregated forms of the α-Synuclein (Syn) protein is the main cause of neurotoxicity in PD by disrupting cellular homeostasis until neuronal death. Scientific research is constantly looking for natural products as preventive agents against the progression of several neurodisorders due their safety and non-toxic nature. Neuroprotective phytochemicals include Maysin (Mys), the most abundant C-glycosilflavone in corn silk. In this work, the Mys protective role against damage by Syn amyloid aggregates - oligomers and fibrils - was investigated in SH-SY5Y human neuroblastoma cells obtaining novel and interesting information concerning the Mys molecular mechanism of action. Mys showed effectiveness in preventing the typical toxic events induced by Syn amyloid aggregates, i.e. oxidative stress and imbalance of intracellular calcium homeostasis. Mys exhibited a cytoprotective role, especially against Syn oligomers injury, activating an autophagic degradative process, thus playing a key role on several features of amyloid neurotoxicity. Therefore, Mys could be proposed for the first time to the scientific community as an interesting novel natural compound that might allow to develop alternative strategies to prevent the damage of Syn oligomers involved in Parkinson's disease.

In vitro anti-glycation activity of the marine plant Posidonia oceanica (L.) Delile.

ETHNOPHARMACOLOGICAL RELEVANCE: The marine plant Posidonia oceanica (L.) Delile is traditionally used by villagers of the west coast of Anatolia as a remedy for diabetes and hypertension. AIM OF THE STUDY: The aim of this study was to explore the role of the P. oceanica hydroalcoholic leaves extract (POE) against human serum albumin glycation. MATERIAL AND METHODS: Advanced glycation end products (AGEs) were obtained with the albumin-glucose in vitro assay. The AGEs intrinsic fluorescence intensity and the electrophoretic migration under native conditions allowed us to verify the effective glycation of albumin. The presence of POE during glycation process was intended to evaluate its anti-glycation role. RESULTS: POE exhibited a strong in vitro anti-glycation ability which occurred independently from its known antioxidant property. CONCLUSIONS: Overall, the antidiabetic, antioxidant, anti-inflammatory and anti-glycation properties of POE could be exploited as an effective tool against diabetes and related complications.

Anti-inflammatory properties of the marine plant Posidonia oceanica (L.) Delile.

ETHNOPHARMACOLOGICAL RELEVANCE: Posidonia oceanica (L.) Delile is an endemic seagrass of the Mediterranean Sea whose use has been documented as a traditional herbal remedy for diabetes and hypertension. Our recently described Posidonia oceanica leaves extract is a phytocomplex endowed with interesting bioactivities, including the inibitory property on human cancer cell migration. AIM OF THE STUDY: The aim of this study was to investigate the anti-inflammatory effects of P. oceanica extract underlying its mechanism of action. MATERIALS AND METHODS: We explored the anti-inflammatory effects of P. oceanica extract on RAW264.7 murine macrophages activated by LPS. We investigated the reactive oxygen species (ROS) and nitric oxide (NO) production and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Then, we examined P. oceanica extract role on the regulation of NF-κB signaling pathway. RESULTS: P. oceanica phytocomplex exhibited a strong ability to inhibit oxidative stress by affecting the production of both ROS and NO and to reduce iNOS and COX-2 levels. In addition, it was evidenced its anti-inflammatory role via inhibiting NF-κB signaling pathway through modulation of ERK1/2 and Akt intracellular cascades. CONCLUSIONS: Our results recognize an anti-inflammatory role of P. oceanica phytocomplex particularly emphasizing its cell safe mechanism of action. In conclusion, the marine plant P. oceanica may be of great interest for scientific research as a source of promising molecules for designing alternative strategies to the conventional treatment of inflammatory diseases.

Comparison of Chitosan Nanoparticles and Soluplus Micelles to Optimize the Bioactivity of Posidonia oceanica Extract on Human Neuroblastoma Cell Migration.

Posidonia oceanica (L.) Delile is a marine plant endemic of Mediterranean Sea endowed with interesting bioactivities. The hydroalcholic extract of P. oceanica leaves (POE), rich in polyphenols and carbohydrates, has been shown to inhibit human cancer cell migration. Neuroblastoma is a common childhood extracranial solid tumor with high rate of invasiveness. Novel therapeutics loaded into nanocarriers may be used to target the migratory and metastatic ability of neuroblastoma. Our goal was to improve both the aqueous solubility of POE and its inhibitory effect on cancer cell migration. METHODS: Chitosan nanoparticles (NP) and Soluplus polymeric micelles (PM) loaded with POE have been developed. Nanoformulations were chemically and physically defined and characterized. In vitro release studies were also performed. Finally, the inhibitory effect of both nanoformulations was tested on SH-SY5Y cell migration by wound healing assay and compared to that of unformulated POE. RESULTS: Both nanoformulations showed excellent physical and chemical stability during storage, and enhanced the solubility of POE. PM-POE improved the inhibitory effect of POE on cell migration probably due to the high encapsulation efficiency and the prolonged release of the extract. CONCLUSIONS: For the first time, a phytocomplex of marine origin, i.e., P. oceanica extract, has enhanced in terms of acqueous solubility and bioactivity once encapsulated inside nanomicelles.

Oxadiazon affects the expression and activity of aldehyde dehydrogenase and acylphosphatase in human striatal precursor cells: A possible role in neurotoxicity.

Exposure to herbicides can induce long-term chronic adverse effects such as respiratory diseases, malignancies and neurodegenerative diseases. Oxadiazon, a pre-emergence or early post-emergence herbicide, despite its low acute toxicity, may induce liver cancer and may exert adverse effects on reproductive and on endocrine functions. Unlike other herbicides, there are no indications on neurotoxicity associated with long-term exposure to oxadiazon. Therefore, we have analyzed in primary neuronal precursor cells isolated from human striatal primordium the effects of non-cytotoxic doses of oxadiazon on neuronal cell differentiation and migration, and on the expression and activity of the mitochondrial aldehyde dehydrogenase 2 (ALDH2) and of the acylphosphatase (ACYP). ALDH2 activity protects neurons against neurotoxicity induced by toxic aldehydes during oxidative stress and plays a role in neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease. ACYP is involved in ion transport, cell differentiation, programmed cell death and cancer, and increased levels of ACYP have been revealed in fibroblasts from patients affected by Alzheimer's disease. In this study we demonstrated that non-cytotoxic doses of oxadiazon were able to inhibit neuronal striatal cell migration and FGF2- and BDNF-dependent differentiation towards neuronal phenotype, and to inhibit the expression and activity of ALDH2 and to increase the expression and activity of ACYP2. In addition, we have provided evidence that in human primary neuronal precursor striatal cells the inhibitory effects of oxadiazon on cell migration and differentiation towards neuronal phenotype were achieved through modulation of ACYP2. Taken together, our findings reveal for the first time that oxadiazon could exert neurotoxic effects by impairing differentiative capabilities of primary neuronal cells and indicate that ALDH2 and ACYP2 are relevant molecular targets for the neurotoxic effects of oxadiazon, suggesting a potential role of this herbicide in the onset of neurodegenerative diseases.

Bioactive Compounds from Posidonia oceanica (L.) Delile Impair Malignant Cell Migration through Autophagy Modulation.

Posidonia oceanica (L.) Delile is a marine plant with interesting biological properties potentially ascribed to the synergistic combination of bioactive compounds. Our previously described extract, obtained from the leaves of P. oceanica, showed the ability to impair HT1080 cell migration by targeting both expression and activity of gelatinases. Commonly, the lack of knowledge about the mechanism of action of phytocomplexes may be an obstacle regarding their therapeutic use and development. The aim of this study was to gain insight into the molecular signaling through which such bioactive compounds impact on malignant cell migration and gelatinolytic activity. The increase in autophagic vacuoles detected by confocal microscopy suggested an enhancement of autophagy in a time and dose dependent manner. This autophagy activation was further confirmed by monitoring pivotal markers of autophagy signaling as well as by evidencing an increase in IGF-1R accumulation on cell membranes. Taken together, our results confirm that the P. oceanica phytocomplex is a promising reservoir of potent and cell safe molecules able to defend against malignancies and other diseases in which gelatinases play a major role in progression. In conclusion, the attractive properties of this phytocomplex may be of industrial interest in regard to the development of novel health-promoting and pharmacological products for the treatment or prevention of several diseases.

Hydrophilic extract from Posidonia oceanica inhibits activity and expression of gelatinases and prevents HT1080 human fibrosarcoma cell line invasion.

Posidonia oceanica (L.) Delile is an endemic Mediterranean sea-grass distributed in the infralittoral zones, where it forms meadows playing a recognized ecological role in the coastal marine habitat. Although its use as a traditional herbal remedy is poorly documented, recent literature reports interesting pharmacological activities as antidiabetic, antioxidant and vasoprotective. Differently from previous literature, this study presents a hydrophilic extraction method that recovers metabolites that may be tested in biological buffers. We showed for the first time in the highly invasive HT1080 human fibrosarcoma cell line that our hydrophilic extract from P. oceanica was able to strongly decrease gene and protein expression of gelatinases MMP-2 and MMP-9 and to directly inhibit in a dose-dependent manner gelatinolytic activity in vitro. Moreover, we have revealed that our extract strongly inhibited HT1080 cell migration and invasion. Biochemical analysis of the hydrophilic extract showed that catechins were the major constituents with minor contribution of gallic acid, ferulic acid and chlorogenic plus a fraction of uncharacterized phenols. However, if each individual compound was tested independently, none by itself was able to induce a direct inhibition of gelatinases as strong as that observed in total extract, opening up new routes to the identification of novel compounds. These results indicate that our hydrophilic extract from P. oceanica might be a source of new pharmacological natural products for treatment or prevention of several diseases related to an altered MMP-2 and MMP-9 expression.

Multifaceted roles of BDNF and FGF2 in human striatal primordium development. An in vitro study.

Grafting fetal striatal cells into the brain of Huntington's disease (HD) patients has raised certain expectations in the past decade as an effective cell-based-therapy for this devastating condition. We argue that the first requirement for successful transplantation is defining the window of plasticity for the striatum during development when the progenitor cells, isolated from their environment, are able to maintain regional-specific-identity and to respond appropriately to cues. The primary cell culture from human fetal striatal primordium described here consists of a mixed population of neural stem cells, neuronal-restricted progenitors and striatal neurons. These cells express trophic factors, such as BDNF and FGF2. We show that these neurotrophins maintain cell plasticity, inducing the expression of neuronal precursor markers and cell adhesion molecules, as well as promoting neurogenesis, migration and survival. We propose that BDNF and FGF2 play an important autocrine-paracrine role during early striatum development in vivo and that their release by fetal striatal grafts may be relevant in the setting of HD cell therapy.