Anti-Inflammatory Activity of Cyanobacteria Pigment Extracts: Physiological Free Radical Scavenging and Modulation of iNOS and LOX Activity.

Cyanobacteria are among the oldest organisms colonizing Earth. Their great biodiversity and ability to biosynthesize secondary metabolites through a variety of routes makes them attractive resources for biotechnological applications and drug discovery. In this pioneer study, four filamentous cyanobacteria (Cephalothrix lacustris LEGE 15493, Leptolyngbya boryana LEGE 15486, Nodosilinea nodulosa LEGE 06104 and Leptothoe sp. LEGE 11479) were explored for their anti-inflammatory potential in cell and cell-free in vitro bioassays, involving different inflammatory mediators and enzymes. Extracts of different polarities were sequentially prepared and chemically characterized for their content of phycobiliproteins (PBPs) and carotenoids. HPLC-PDA analysis of the acetone extracts revealed ß-carotene to be the dominant carotenoid (18.4-44.3 mg/g) and zeaxanthin as the dominant xanthophyll (52.7-192.9 mg/g), with Leptothoe sp. LEGE 11479 and Nodosilinea nodulosa LEGE 06104, respectively, being the richest strains. The PBP profile was in accordance with the color presented by the aqueous extracts, with Leptolyngbya boryana LEGE 15486 being the richest in phycocyanin (204.5 µg/mg) and Leptothoe sp. LEGE 11479 the richest in phycoerythrin (78.5 µg/mg). Aqueous extracts were more effective in superoxide anion radical scavenging, while acetone ones were more effective in scavenging nitric oxide radical (●NO) and in inhibiting lipoxygenase. Acetone extracts also reduced ●NO production in lipopolysaccharide-stimulated RAW 264.7 macrophages, with the mechanistic study suggesting a downregulation of the inducible nitric oxide synthase expression. Nodosilinea nodulosa LEGE 06104 and Leptothoe sp. LEGE 11479 acetone extracts presented the lowest IC50 values for the mentioned assays, pointing them out as promising resources for the development of new multi-target anti-inflammatory therapies.

Antioxidant, Anti-Inflammatory and Anti-Obesity Potential of Extracts Containing Phenols, Chlorophyll and Carotenoids from Mexican Wild Populations of Bacopa monnieri (L.) Wettst.

Some of the species of the genus Bacopa have been used in Pharmacopoeia worldwide. However, in Mexico, Bacopa monnieri has neither been extensively cultivated nor studied, nor has their use in traditional medicine been reported. The aim of this work was to assess the taxonomic verification of the four wild populations of B. monnieri, the chemical content of their pigments and phenols and to provide an analysis of their potential bioactivity. B. monnieri wild populations from Mexico were validated using molecular markers. Chromatographic profiling using HPLC-PDA revealed 21 compounds comprising 12 chlorophylls and nine carotenoids; of the latter, the major ones were lutein (0.921 ± 0.031 µg/mg of dry extract) and ß-carotene (0.095 ± 0.003 µg/mg of dry extract). The total phenolic content, determined using the Folin-Ciocalteu assay, ranged from 54.8 ± 5.8 to 70.3 ± 2.2 µg of gallic acid equivalents (GAE)/mg. Plant extracts scavenged from the free radical DPPH in IC50 ranged from 130.6 ± 3.0 to 249.9 ± 12.1 µg dry extract/mL. In terms of the anti-inflammatory potential, the most effective extract was from a soil-based plant from Jalisco (BS), reduced from nitric oxide in a RAW 264.7 culture medium, with an IC50 value of 134 µg of dry extract/mL. The BS extract showed a significant neutral lipid-reducing activity in the zebrafish model, ranging from 3.13 µg/mL p < 0.05 to 100 µg/mL p < 0.0001. Overall, the extracts analyzed here for the first time seem promising for future use because of their antioxidant, anti-inflammatory and anti-obesity potential.

From sugarcane to skin: Lignin as a multifunctional ingredient for cosmetic application.

Lignin has been suggested as a promising candidate for cosmetic applications due to its remarkable potential to absorb ultraviolet rays and distinctive antioxidant activity. This study aims at evaluating the performance of lignin from sugarcane bagasse (SCB) as natural UV blocker, antioxidant, and pigment. Lignin was extracted from SCB, characterized and incorporated into a blemish balm (BB) cream. The biological potential, concretely, in vitro and in vivo sun protection factor (SPF) and in vitro UVA-PF, and safety were assessed. A high-purity SCB lignin (>92 %) was obtained by a mild alkaline extraction process. The results of cytotoxicity, mutagenicity, skin sensitization and in vivo acute cutaneous irritation demonstrated that SCB lignin is safe for topical applications. Lignin showed capacity to scavenge both ABTS and DPPH radicals, which were preserved after its incorporation into the cosmetic formulation. Notable results were achieved in terms of in vitro and in vivo SPF of 9.5 ± 2.9 and 9.6 ± 0.8, respectively. Furthermore, the tested lignin-based BB cream revealed a broad-spectrum UV protection (critical wavelength of 378 ± 0.5 nm). These results suggest SCB lignin as multifunctional and safe ingredient for use in cosmetic products.

Cosmetic Application of Cyanobacteria Extracts with a Sustainable Vision to Skincare: Role in the Antioxidant and Antiaging Process.

Nature-based and sustainably sourced cosmetics have been dominating the area of skincare products worldwide. Due to their antioxidant and antiaging properties, compounds from cyanobacteria, such as carotenoids and phycobiliproteins, may replace synthetic ingredients in cosmetic formulations and may be used in products such as sunscreens, skincare creams, and makeup. In this study, we evaluated the potential of acetonic and aqueous extracts from cyanobacteria strains of the genera Cyanobium and Leptothoe and from strains within Synechococcales and Oscillatoriales orders, for use in cosmetics. Extractions were sequentially performed with acetone and water. Extracts were firstly analyzed for their toxicity to keratinocytes, fibroblasts, and endothelial cells (HaCAT, 3T3L1 and hCMEC/D3, respectively). The non-cytotoxic extracts were characterized in terms of total proteins, carotenoids, chlorophyll, phenols, phycobiliproteins, and analyzed for their antioxidant potential against the superoxide anion radical (O2•−), and for their ability to inhibit key enzymes associated with the skin aging process. Aqueous extracts were richer in total proteins and phycobiliproteins. The aqueous extracts of Synechococcales cyanobacterium LEGE 181157 and Synechococcales cyanobacterium LEGE 181150 showed the highest value for total proteins (760.81 and 695.25 µg BSA mL−1dry extract, respectively) and the best values regarding O2•− scavenging (IC50 = 63.24 and 112.18 µg mL−1dry extract, respectively) with a significant negative correlation observed (p < 0.01). Moreover, aqueous extracts of Synechococcales cyanobacterium LEGE 181150 and Synechococcales cyanobacterium LEGE 181157 inhibited hyaluronidase, (IC50 of 483.86 and 645.06 µg mL−1dry extract, respectively), with a significant negative correlation with total proteins (p < 0.05), pointing out the contribution of these compounds to the biological activities observed. Acetonic extracts were richer in carotenoids and phenols. Zeaxanthin and ß-carotene were predominant among all strains, being present in higher amount in Cyanobium sp. LEGE 07175 (53.08 µg mg−1) and Leptothoe sp. LEGE 181156 (47.89 µg mg−1), respectively. The same strains also showed the highest values for collagenase inhibition at 750 µg mL−1dry extract (32.88 and 36.61%, respectively). Furthermore, Leptothoe sp. LEGE 181156 exhibited the lowest IC50 value for tyrosinase inhibition (465.92 µg mL−1dry extract) and Synechococcales cyanobacterium LEGE 181157 presented the best values for elastase inhibition (IC50 of 380.50 and IC25 of 51.43 µg mL−1dry extract). In general, cyanobacteria extracts demonstrated potential for being used for antiaging purposes, with aqueous extracts being more efficient at free radicals scavenging and acetonic ones at avoiding degradation of dermal matrix components.

Camel Grass Phenolic Compounds: Targeting Inflammation and Neurologically Related Conditions.

BACKGROUND: The use of plants for therapeutic purposes has been supported by growing scientific evidence. METHODS: This work consisted of (i) characterizing the phenolic compounds present in both aqueous and hydroethanol (1:1, v/v) extracts of camel grass, by hyphenated liquid chromatographic techniques, (ii) evaluating their anti-inflammatory, antioxidant, and neuromodulation potential, through in vitro cell and cell-free models, and (iii) establishing a relationship between the chemical profiles of the extracts and their biological activities. RESULTS: Several caffeic acid and flavonoid derivatives were determined in both extracts. The extracts displayed scavenging capacity against the physiologically relevant nitric oxide (•NO) and superoxide anion (O2•-) radicals, significantly reduced NO production in lipopolysaccharide (LPS)-stimulated macrophages (RAW 264.7), and inhibited the activity of hyaluronidase (HAase), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Some of these bioactivities were found to be related with the chemical profile of the extracts, namely with 3-caffeoylquinic, 4-caffeoylquinic, chlorogenic, and p-coumaric acids, as well as with luteolin and apigenin derivatives. CONCLUSIONS: This study reports, for the first time, the potential medicinal properties of aqueous and hydroethanol extracts of camel grass in the RAW 264.7 cell model of inflammation, and in neurologically related conditions.

Phenolic Compounds' Occurrence in Opuntia Species and Their Role in the Inflammatory Process: A Review.

Within the Cactaceae family, Opuntia comprises the most widespread species, with a recognized importance in human life, including feeding, domestic use as home natural barriers, and as a traditional remedy for diverse diseases and conditions such asthma, edema, and burns. Indeed, scientific reports have stated that these health benefits may be due to various active compounds, particularly polyphenols, which are ubiquitously found in plants and have proven their pharmacological efficiency by displaying antimicrobial, anti-cancer, and anti-inflammatory activities, among others. Opuntia species contain different classes of phenolic compounds that are recognized for their anti-inflammatory potential. Among them, quercetin, isorhamnetin, and kaempferol derivates were reported to greatly contribute to modulate cells' infiltration and secretion of soluble inflammatory mediators, with key implications in the inflammatory process. In this review, we make a summary of the different classes of phenolic compounds reported in Opuntia species so far and explore their implications in the inflammatory process, reported by in vitro and in vivo bioassays, supporting the use of cactus in folk medicine and valorizing them from the socio-economic point of view.

Cyanobacteria Secondary Metabolites as Biotechnological Ingredients in Natural Anti-Aging Cosmetics: Potential to Overcome Hyperpigmentation, Loss of Skin Density and UV Radiation-Deleterious Effects.

The loss of density and elasticity, the appearance of wrinkles and hyperpigmentation are among the first noticeable signs of skin aging. Beyond UV radiation and oxidative stress, matrix metalloproteinases (MMPs) assume a preponderant role in the process, since their deregulation results in the degradation of most extracellular matrix components. In this survey, four cyanobacteria strains were explored for their capacity to produce secondary metabolites with biotechnological potential for use in anti-aging formulations. Leptolyngbya boryana LEGE 15486 and Cephalothrix lacustris LEGE 15493 from freshwater ecosystems, and Leptolyngbya cf. ectocarpi LEGE 11479 and Nodosilinea nodulosa LEGE 06104 from marine habitats were sequentially extracted with acetone and water, and extracts were analyzed for their toxicity in cell lines with key roles in the skin context (HaCAT, 3T3L1, and hCMEC). The non-toxic extracts were chemically characterized in terms of proteins, carotenoids, phenols, and chlorophyll a, and their anti-aging potential was explored through their ability to scavenge the physiological free radical superoxide anion radical (O2•−), to reduce the activity of the MMPs elastase and hyaluronidase, to inhibit tyrosinase and thus avoid melanin production, and to block UV-B radiation (sun protection factor, SPF). Leptolyngbya species stood out for anti-aging purposes: L. boryana LEGE 15486 presented a remarkable SPF of 19 (at 200 µg/mL), being among the best species regarding O2•− scavenging, (IC50 = 99.50 µg/mL) and also being able to inhibit tyrosinase (IC25 = 784 µg/mL), proving to be promising against UV-induced skin-aging; L. ectocarpi LEGE 11479 was more efficient in inhibiting MMPs (hyaluronidase, IC50 = 863 µg/mL; elastase, IC50 = 391 µg/mL), thus being the choice to retard dermal density loss. Principal component analysis (PCA) of the data allowed the grouping of extracts into three groups, according to their chemical composition; the correlation of carotenoids and chlorophyll a with MMPs activity (p < 0.01), O2•− scavenging with phenolic compounds (p < 0.01), and phycocyanin and allophycocyanin with SPF, pointing to these compounds in particular as responsible for UV-B blockage. This original survey explores, for the first time, the biotechnological potential of these cyanobacteria strains in the field of skin aging, demonstrating the promising, innovative, and multifactorial nature of these microorganisms.

Karlodinium veneficum: Growth optimization, metabolite characterization and biotechnological potential survey.

AIM OF THIS STUDY: The major aim of this work was to consistently optimize the production of biomass of the dinoflagellate Karlodinium veneficum and evaluate its extracts biotechnological potential application towards food, nutraceutical or/and pharmaceutical industries. METHODS AND RESULTS: A successful approach of biomass production of K. veneficum CCMP 2936 was optimized along with the chemical characterization of its metabolite profile. Several temperatures (12, 16, 20, 25, 30°C), L1 nutrient concentrations (0.5×, 2×, 2.5×, 3×) and NaCl concentrations (20, 25, 30, 40 g L-1 ) were tested. The growth rate was maximum at 16°C, 2× nutrient concentration and 40 g L-1 of NaCl; hence, these conditions were chosen for bulk production of biomass. Methanolic extracts were prepared, and pigments, lipids and phenolic compounds were assessed; complemented by antioxidant and anti-inflammatory capacities, and cytotoxicity. Fucoxanthin and derivatives accounted for 0.06% of dry weight, and up to 60% (w/w) of all quantified metabolites were lipids. Said extracts displayed high antioxidant capacity, as towards assessed via the NO•- and ABTS•+ assays (IC50  = 109.09 ± 6.73 and 266.46 ± 2.25 µgE  ml-1 , respectively), unlike observed via the O2 •- assay (IC25 reaching 56.06 ± 5.56 µgE  ml-1 ). No signs of cytotoxicity were observed. CONCLUSIONS: Karlodinium veneficum biomass production was consistently optimized in terms of temperature, L1 nutrient concentrations and NaCl concentration. In addition, this strain appears promising for eventual biotechnological exploitation. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides fundamental insights about the growth and potential of value-added compounds of dinoflagellate K. veneficum. Dinoflagellates, as K. veneficum are poorly studied regarding its biomass production and added-value compounds for potential biotechnological exploitation. These organisms are difficult to maintain and grow in the laboratory. Thus, any fundamental contribution is relevant to share with the scientific community.

Cyanobacteria and microalgae bioactive compounds in skin-ageing: potential to restore extracellular matrix filling and overcome hyperpigmentation.

As the largest organ in human body, skin acts as a physicochemical barrier, offering protection against harmful environmental stressors, such as chemicals, pathogens, temperature and radiation. Nonetheless, skins prominence goes further, with a significant psychosocial role in an increasingly ageing population. Prompted by consumers' concern regarding skincare, cosmetic industry has been developing new formulas capable of lessening the most visible signs of ageing, including reduction in skin density and elasticity, wrinkling and hyperpigmentation. Allied to skincare is the rising importance set on natural products, sustainably obtained from less environmental impacting methods. Cyanobacteria and microalgae are adding importance in this field, given their ability to biosynthesize secondary metabolites with anti-ageing potential. In this review, we present an overview on the potential of cyanobacteria and microalgae compounds to overcome skin-ageing, essentially by exploring their effects on the metalloproteinases collagenase, elastase, gelatinase and hyaluronidase, and in other enzymes involved in the pigmentation process.

Exploitation of Filamentous and Picoplanktonic Cyanobacteria for Cosmetic Applications: Potential to Improve Skin Structure and Preserve Dermal Matrix Components.

The use of natural products in skin care formulations gained interest as a concern for modern societies. The undesirable side effects of synthetic COMPOUNDS, as well as the associated environmental hazards, have driven investigation on photosynthetic organisms as sustainable sources of effective and environmentally friendly ingredients. The use of natural extracts in cosmetics has been highlighted and, along with plants and algae, cyanobacteria have come into focus. Due to their low culture demands, high grow rates and ability to produce a wide variability of bioactive metabolites, cyanobacteria emerged as an economic and sustainable base for the cosmetic industry. In this study, we evaluated the potential of ethanol extracts of picocyanobacteria strains of the genera Cyanobium and Synechocystis and filamentous strains of the genera Nodosilinea, Phormidium and Tychonema for skin applications, with focus in the field of anti-aging. The extracts were analyzed for their pigment profile, phenolic content, antioxidant potential, cytotoxicity against keratinocytes (HaCat), fibroblasts (3T3L1), endothelial cells (hCMEC/D3) and capacity to inhibit hyaluronidase (HAase). The total carotenoid content ranged from 118.69 to 383.89 µg g-1 of dry biomass, and the total phenolic content from 1.07 to 2.45 mg GAE g-1. Identified carotenoids consisted of zeaxanthin, lutein, canthaxanthin, echinenone and ß-carotene, with zeaxanthin and lutein being the most representative (49.82 and 79.08 µg g-1, respectively). The highest antioxidant potential was found for Phormidium sp. LEGE 05292 and Tychonema sp. LEGE 07196 for superoxide anion radical (O2•-) scavenging (IC50 of 822.70 and 924 µg mL-1, respectively). Low or no cytotoxicity was registered. Regarding HAase inhibition, Tychonema sp. LEGE 07196 and Cyanobium sp. LEGE 07175 showed the best IC50 (182.74 and 208.36 µg mL-1, respectively). In addition, an increase in fibroblast proliferation was registered with these same strains. From this work, the ethanol extracts of the species Tychonema sp. and Cyanobium sp. are particularly interesting for their potential application in anti-aging formulations, once they stimulated fibroblast proliferation and inhibit hyaluronic acid digestion.

White and red LEDs as two-phase batch for cyanobacterial pigments production.

Carotenoids and phycobiliproteins have a high economic value, due to their wide range of biological and industrial applications. The implementation of strategies to increase their production, such as the application of two-phase light cultivation systems, can stimulate pigments production, increasing economic turnover. In this sense, Cyanobium sp. was grown in seven different two-phase white/red cultivation arrangements, varying the time of each light from 0 to 21 days. Biomass, photosynthetic activity, pigments profile and antioxidant capacity were measured along time. Red light increased photosynthetic activity and pigments content (ca. 1.8-fold), and the use of a two-phase cultivation system generally raised bioactivity and production of phytochemicals. Among the studied, the optimal cultivation condition was found with 10 days of white followed by 4 days of red light. The optimized growth led to a productivity of 137.4 ± 0.8 mg L-1 d-1 of biomass, 17.0 ± 0.2 mg L-1 d-1 of total phycobiliproteins and 4.5 ± 0.2 mg L-1 d-1 of carotenoids.

Carotenoids from Cyanobacteria: A Biotechnological Approach for the Topical Treatment of Psoriasis.

In this study, five cyanobacteria strains (Alkalinema aff. pantanalense LEGE15481, Cyanobium gracile LEGE12431, Nodosilinea (Leptolyngbya) antarctica LEGE13457, Cuspidothrix issatschenkoi LEGE03282 and Leptolyngbya-like sp. LEGE13412) from the Blue Biotechnology and Ecotoxicology Culture Collection (LEGE CC) of CIIMAR were explored for their biotechnological potential in the treatment of psoriasis. Different extracts were characterized for their pigment profile by HPLC-PDA. The antioxidant potential of the extracts was assessed against the superoxide anion radical (O2•-). Their anti-inflammatory and antiproliferative potential was assessed in vitro using the macrophages RAW 264.7 and the human keratinocytes HaCaT as cell-line models, respectively. Terrestrial and freshwater strains presented the highest carotenoid content (33193-63926 µg/g dry extract), with all-trans-ß-carotene, zeaxanthin, echinenone and lutein derivatives being the most abundant carotenoids. Acetone was the most effective solvent for pigment extraction. The acetone extracts presented the lowest IC50 values (0.29-0.38 mg dry extract/mL) regarding O2•- scavenging, and revealed anti-inflammatory potential, with N. antarctica LEGE13457, A. pantanalense LEGE15481 and Leptolyngbya-like sp. LEGE13412 reducing the nitric oxide (NO) in RAW 264.7 cell culture medium in about 25% (p < 0.05). With the exception of A. pantanalense LEGE15481, all the extracts significantly reduced keratinocyte proliferation (p < 0.05), demonstrating a selective toxicity among the different cell lines. Overall, Leptolyngbya-like sp. LEGE13412 and N. antarctica LEGE13457 seem promising for further exploitation in the framework of psoriasis, due to their antioxidant, anti-inflammatory and antiproliferative potential.

Dietary Creatine Supplementation in Gilthead Seabream (Sparus aurata) Increases Dorsal Muscle Area and the Expression of myod1 and capn1 Genes.

Creatine (Cr) is an amino acid derivative with an important role in the cell as energy buffer that has been largely used as dietary supplement to increase muscle strength and lean body mass in healthy individuals and athletes. However, studies in fish are scarce. The aim of this work is to determine whether dietary Cr supplementation affects muscle growth in gilthead seabream (Sparus aurata) juveniles. Fish were fed ad libitum for 69 days with diets containing three increasing levels of creatine monohydrate (2, 5, and 8%) that were compared with a non-supplemented control (CTRL) diet. At the end of the trial, the fast-twist skeletal muscle growth dynamics (muscle cellularity) and the expression of muscle-related genes were evaluated. There was a general trend for Cr-fed fish to be larger and longer than those fed the CTRL, but no significant differences in daily growth index (DGI) were registered among dietary treatments. The dorsal cross-sectional muscle area (DMA) of fish fed Cr 5 and Cr 8% was significantly larger than that of fish fed CTRL. The groups supplemented with Cr systematically had a higher relative number of both small-sized (≤20 µm) and large-sized fibers (≥120 µm). Dorsal total fibers number was highest in fish fed 5% Cr. In fish supplemented with 5% Cr, the relative expression of myogenic differentiation 1 (myod1) increased almost four times compared to those fed the CTRL diet. The relative expression of calpain 3 (capn3) was highest in fish fed diets with 2% Cr supplementation, but did not differ significantly from those fed the CTRL or Cr 5%. The myod1 gene expression had a positive and significant correlation with that of capn1, capns1a, and capn3 expression. These results suggest that the observed modulation of gene expression was not enough to produce a significant alteration in muscle phenotype under the tested conditions, as a non-significant increase in muscle fiber diameter and higher total number of fiber was observed, but still resulted in increased DMA. Additional studies may be required in order to better clarify the effect of dietary Cr supplementation in fish, possibly in conjunction with induced resistance training.

Edible seaweeds' phlorotannins in allergy: A natural multi-target approach.

The anti-allergenicity of phlorotannin-targeted extracts from four edible seaweed species of Fucus genus was evaluated herein for the first time. Extracts were able to act upon cellular events triggered by immunological reaction (IgE/antigen), and on cellular events downstream the Ca2+ influx caused by a chemical stimulus (calcium ionophore A23187), preventing degranulation of RBL-2H3 cells. Furthermore, a dose-dependent behaviour towards allergy-related enzymatic systems was observed for all the phlorotannin extracts. Linear correlations were found between reduction of the allergic mediators released and the total phlorotannin content, as well as between the enzyme inhibition and the amount of phlorotannins in the extracts. These results point to a multi-target anti-allergic capacity of phlorotannin-targeted extracts, which displayed effects on different critical steps of the allergic response, contributing to the valorisation of Fucus spp. both as food and for nutraceutical applications.

Total substitution of dietary fish oil by vegetable oils stimulates muscle hypertrophic growth in Senegalese sole and the upregulation of fgf6.

The long term effects of fish oil (FO) substitution by increasing the levels of vegetable oils (VO), 0% (CTR), 50% (VO50) and 100% (VO100), in diets for Senegalese sole were evaluated in terms of skeletal muscle cellularity and expression of related genes. After 140 days of feeding, all fish had similar body weight and length. The inclusion of 50% VO did not result in differences in muscle cellularity, but dorsal muscle cross-sectional area and fast-twitch fibre diameter increased in fish fed total FO substitution, whilst fibre density was reduced (P < 0.05) in relation to CTR. The total number of fibres was similar in all treatments. FO substitution did not affect the transcript levels of myogenic genes (myf5, mrf4, myog, myod1, myod2), but resulted in a two-fold increase of fgf6 transcript levels compared to CTR (P < 0.05). The relative expression of igf-I was higher in VO100 than in VO50, but was similar to CTR. FO substitution resulted in cellularity changes related to the stimulation of muscle hypertrophic growth, but not hyperplastic growth, and associated with a nutritional modulation of fgf6 by dietary VO. This study indicates that 50% VO does not affect the muscle phenotype, but total FO substitution stimulates muscle hypertrophy.

Natural Products: An Alternative to Conventional Therapy for Dermatophytosis?

The increased incidence of fungal infections, associated with the widespread use of antifungal drugs, has resulted in the development of resistance, making it necessary to discover new therapeutic alternatives. Among fungal infections, dermatophytoses constitute a serious public health problem, affecting 20-25 % of the world population. Medicinal plants represent an endless source of bioactive molecules, and their volatile and non-volatile extracts are clearly recognized for being the historical basis of therapeutic health care. Because of this, the research on natural products with antifungal activity against dermatophytes has considerably increased in recent years. However, despite the recognized anti-dermatophytic potential of natural products, often advantageous face to commercial drugs, there is still a long way to go until their use in therapeutics. This review attempts to summarize the current status of anti-dermatophytic natural products, focusing on their mechanism of action, the developed pharmaceutical formulations and their effectiveness in human and animal models of infection.

Phlorotannins: Towards New Pharmacological Interventions for Diabetes Mellitus Type 2.

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycaemia, and predicted by the World Health Organization as the expected 7th leading cause of death in 2030. Diabetes mellitus type 2 (DMT2) comprises the majority of diabetic individuals around the world (90%-95%). Pathophysiologically, this disorder results from a deregulation of glucose homeostasis, worsened by overweight and by a sedentary lifestyle, culminating in life-threatening cardiovascular events. The currently available anti-diabetic drugs are not devoid of undesirable side effects, sometimes responsible for poor therapeutic compliance. This represents a challenge for contemporary medicine, and stimulates research focused on the development of safer and more efficient anti-diabetic therapies. Amongst the most promising sources of new bioactive molecules, seaweeds represent valuable, but still underexploited, biofactories for drug discovery and product development. In this review, the role of phlorotannins, a class of polyphenols exclusively produced by brown seaweeds, in the management of DMT2 will be discussed, focusing on various pharmacologically relevant mechanisms and targets, including pancreatic, hepatic and intestinal enzymes, glucose transport and metabolism, glucose-induced toxicity and ß-cell cytoprotection, and considering numerous in vitro and in vivo surveys.

Screening of a Marine Algal Extract for Antifungal Activities.

Over the past few years algal extracts have become increasingly interesting to the scientific community due to their promising biological properties. Phlorotannin extracts are particularly attractive partly due to their reported antifungal activity against several yeast and dermatophyte strains.The micromethod used for the evaluation of the minimum inhibitory concentration (MIC) and the minimum lethal concentration (MLC) represents an effective and solvent-saving procedure to evaluate the antifungal activity of algae extracts. Here we describe the micromethod for determining the MIC and the MLC of algal extracts by using the example of a purified phlorotannin extract of brown algae.

Antimicrobial Activity and Mechanism of Action of New N-Heteroaryl-1H-(benz)Imidazoles.

The antimicrobial activity of sixteen new N-heteroarylated 1H-(benz)imidazoles was evaluated against clinically relevant bacteria (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and fungi (Candida, Aspergillus and dermatophyte) species according to the Clinical and Laboratory Standards Institute guidelines. None of the tested compounds were active against Gram negative bacteria, but only against S. aureus, that was particularly susceptible to N-thianthrenyl- and N-dibenzothienyl imidazole derivatives. Most of the imidazole derivatives showed a broad spectrum of antifungal activity in all tested fungal strains, including fluconazole-resistant species, with a particularly low minimum inhibitory concentration (MIC) for dermatophytes. N-(dibenzofuran-4-yl)-1H-imidazole (1) and N-(dibenzothien-4-yl)-1H-imidazole (3) showed the highest antifungal potential, being most active against C. albicans. Some N-heteroarylated benzimidazoles showed low activity for fungi with the exception of 3-(1H-benzo[d]imidazol-1-yl)quinoline (14) which was selective against dermatophytes (MIC=4-16 µg/mL). The effect of the active compounds in the inhibition of the dimorphic transition, ergosterol biosynthesis and mitochondrial activity was evaluated in Candida albicans. Compounds 1 and 3 showed the capacity to inhibit the germ tube formation in C. albicans, reduced the ergosterol production and impaired the mitochondrial function. Compounds 1 and 3 showed antimicrobial activity and low cytotoxicity, being of interest for further investigation concerning specially the development of new antifungal agents.