Cyclodextrins for the Delivery of Bioactive Compounds from Natural Sources: Medicinal, Food and Cosmetics Applications.

Cyclodextrins have gained significant and established attention as versatile carriers for the delivery of bioactive compounds derived from natural sources in various applications, including medicine, food and cosmetics. Their toroidal structure and hydrophobic cavity render them ideal candidates for encapsulating and solubilizing hydrophobic and poorly soluble compounds. Most medicinal, food and cosmetic ingredients share the challenges of hydrophobicity and degradation that can be effectively addressed by various cyclodextrin types. Though not new or novel-their first applications appeared in the market in the 1970s-their versatility has inspired numerous developments, either on the academic or industrial level. This review article provides an overview of the ever-growing applications of cyclodextrins in the delivery of bioactive compounds from natural sources and their potential application benefits.

Royal Jelly Components Encapsulation in a Controlled Release System-Skin Functionality, and Biochemical Activity for Skin Applications.

Royal jelly is a yellowish-white substance with a gel texture that is secreted from the hypopharyngeal and mandibular glands of young worker bees. It consists mainly of water (50-56%), proteins (18%), carbohydrates (15%), lipids (3-6%), minerals (1.5%), and vitamins, and has many beneficial properties such as antimicrobial, anti-inflammatory, anticancer, antioxidant, antidiabetic, immunomodulatory, and anti-aging. Royal jelly has been used since ancient times in traditional medicine, cosmetics and as a functional food due to its high nutritional value. The main bioactive substances are royalactin, and 10-hydroxy-2-decenoic acid (10-HDA). Other important bioactive molecules with antioxidant and photoprotective skin activity are polyphenols. However, they present difficulties in extraction and in use as they are unstable physicochemically, and a higher temperature causes color change and component degradation. In the present study, a new encapsulation and delivery system consisting of liposomes and cyclodextrins incorporating royal jelly has been developed. The new delivery system aims to the elimination of the stability disadvantages of royal jelly's sensitive component 10-HDA, but also to the controlled release of its ingredients and, more particularly, 10-HDA, for an enhanced bioactivity in cosmeceutical applications.

Applications and Prospects of Nanotechnology in Food and Cosmetics Preservation.

Cosmetic and food products containing water are prone to contamination during the production, storage, and transit process, leading to product spoilage and degraded organoleptic characteristics. The efficient preservation of food and cosmetics is one of the most important issues the industry is facing today. The use of nanotechnology in food and cosmetics for preservation purposes offers the possibility to boost the activity of antimicrobial agents and/or promote their safer distribution into the end product upon incorporation into packaging or film constructions. In this review, current preservation strategies are discussed and the most recent studies in nanostructures used for preservation purposes are categorized and analyzed in a way that hopefully provides the most promising strategies for both the improvement of product safety and shelf-life extension. Packaging materials are also included since the container plays a major role in the preservation of such products. It is conclusively revealed that most of the applications refer to the nanocomposites as part of the packaging, mainly due to the various possibilities that nanoscience offers to this field. Apart from that, the route of exposure being either skin or the gastrointestinal system involves safety concerns, and since migration of nanoparticles (NPs) from their container can be measured, concerns can be minimized. Conclusion: Nanomaterial science has already made a significant contribution to food and cosmetics preservation, and rapid developments in the last years reinforce the belief that in the future much of the preservation strategies to be pursued by the two industries will be based on NPs and their nanocomposites.

Innovative Delivery Systems Loaded with Plant Bioactive Ingredients: Formulation Approaches and Applications.

Plants constitute a rich source of diverse classes of valuable phytochemicals (e.g., phenolic acids, flavonoids, carotenoids, alkaloids) with proven biological activity (e.g., antioxidant, anti-inflammatory, antimicrobial, etc.). However, factors such as low stability, poor solubility and bioavailability limit their food, cosmetics and pharmaceutical applications. In this regard, a wide range of delivery systems have been developed to increase the stability of plant-derived bioactive compounds upon processing, storage or under gastrointestinal digestion conditions, to enhance their solubility, to mask undesirable flavors as well as to efficiently deliver them to the target tissues where they can exert their biological activity and promote human health. In the present review, the latest advances regarding the design of innovative delivery systems for pure plant bioactive compounds, extracts or essential oils, in order to overcome the above-mentioned challenges, are presented. Moreover, a broad spectrum of applications along with future trends are critically discussed.

A New Controlled Release System for Propolis Polyphenols and Its Biochemical Activity for Skin Applications.

Propolis is a resinous substance produced by bees that exhibits antimicrobial, immunostimulatory and antioxidant activity. Its use is common in functional foods, cosmetics and traditional medicine despite the fact that it demonstrates low extraction yields and inconsistency in non-toxic solvents. In this work, a new encapsulation and delivery system consisting of liposomes and cyclodextrins incorporating propolis polyphenols has been developed and characterized. The antioxidant, antimutagenic and antiaging properties of the system under normal and UVB-induced oxidative stress conditions were investigated in cultured skin cells and/or reconstituted skin model. Furthermore, the transcript accumulation for an array of genes involved in many skin-related processes was studied. The system exhibits significant polyphenol encapsulation efficiency, physicochemical stability as well as controlled release rate in appropriate conditions. The delivery system can retain the anti-mutagenic, anti-oxidative and anti-ageing effects of propolis polyphenols to levels similar and comparable to those of propolis methanolic extracts, making the system ideal for applications where non-toxic solvents are required and controlled release of the polyphenol content is desired.

Toxicity Profiling of Biosurfactants Produced by Novel Marine Bacterial Strains.

Surface active agents (SAAs), currently used in modern industry, are synthetic chemicals produced from non-renewable sources, with potential toxic impacts on humans and the environment. Thus, there is an increased interest for the identification and utilization of natural derived SAAs. As such, the marine environment is considered a promising source of biosurfactants with low toxicity, environmental compatibility, and biodegradation compared to their synthetic counterparts. MARISURF is a Horizon 2020 EU-funded project aiming to identify and functionally characterize SAAs, derived from a unique marine bacterial collection, towards commercial exploitation. Specifically, rhamnolipids produced by Marinobacter MCTG107b and Pseudomonas MCTG214(3b1) strains were previously identified and characterized while currently their toxicity profile was assessed by utilizing well-established methodologies. Our results showed a lack of cytotoxicity in in vitro models of human skin and liver as indicated by alamar blue and propidium iodide assays. Additionally, the use of the single gel electrophoresis assay, under oxidative stress conditions, revealed absence of any significant mutagenic/anti-mutagenic potential. Finally, both 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) cell-free assays, revealed no significant anti-oxidant capacity for neither of the tested compounds. Consequently, the absence of significant cytotoxicity and/or mutagenicity justifies their commercial exploitation and potential development into industrial end-user applications as natural and environmentally friendly biosurfactants.

NMR metabolic profiling of Greek propolis samples: Comparative evaluation of their phytochemical compositions and investigation of their anti-ageing and antioxidant properties.

The present study aimed to investigate the metabolic profile, as well as the antioxidant and anti-ageing activities of twenty propolis samples from different regions of Greece. Chemical profiling of methanolic extracts was investigated using HPTLC and 1H-NMR techniques. Their antioxidant activity was evaluated by free radical scavenging methods (DPPH and ABTS), whereas anti-ageing properties were assessed as anti-collagenase activity. Extracts were also investigated in vitro for their ability to inhibit tyrosinase, which is responsible for the oxidation of L-DOPA to dopachrome and the production of melanin. The HPTLC and NMR analysis revealed high variability in the phytochemical profile of the methanolic extracts, with three major groups to be observed: a) Group I, consisting of samples rich in terpenoids, which present low antioxidant but high anti-tyrosinase activity, b) Group II, consisting of samples rich in flavonoids, which form a broad cluster with major similarities at the aromatic region and showed the highest anti-oxidant and anti-collagenase activities and c) Group III, consisting of samples with lower flavonoid content than the samples of Group II, which exhibited moderate antioxidant, anti-collagenase and anti-tyrosinase activities. In conclusion, this study has shown high differentiation on the chromatographic and spectroscopic metabolic profile of Greek propolis samples of different geographical origin, which is also reflected in their biological properties. Their important effects as antioxidant, anti-tyrosinase and anti-collagenase agents make propolis an important potent ingredient in the industry of food supplements and cosmeceuticals. Moreover, a correlation of a particular chemical propolis type to a specific type of biological activity will allow to prepare standardized extracts and develop food supplements and cosmeceuticals possessing the desired pharmacological properties.

In vitro protective effects of Paeonia mascula subsp. hellenica callus extract on human keratinocytes.

Natural ingredients have been used to improve the state of health in humans. The genus Paeonia has been studied only limited yet it's reported to have many activities such as antioxidant and anti-inflammatory. To this context, here we focused on an endemic Paeonia species in Attica. This study aims to present the development of the Paeonia mascula subsp. hellenica callus extract and its pleiotropic bioactivity on human primary keratinocytes exploring its potential application as an active agent in skin-related products. This extract showed a high scavenging activity with high phenolic content and an interesting metabolic profile. At a molecular level, the study on the transcript accumulation of genes revealed that this extract exhibits in vitro skin-related protection properties by mediating mitochondrial energy, cell proliferation, immune and inflammatory response and positively regulates genes involved in epidermal and in stratum corneum function. Besides, the extract is proven not skin irritant on reconstructed human skin model. These findings indicate that the specific P. mascula subsp. hellenica extract possesses significant in vitro protection activity on human epidermis and provides new insights into its beneficial role in skin confirming that the advent of biotechnology contribution the past few decades.

Marine Fungus Aspergillus chevalieri TM2-S6 Extract Protects Skin Fibroblasts from Oxidative Stress.

The strain Aspergillus chevalieri TM2-S6 was isolated from the sponge Axinella and identified according to internal transcribed spacer (ITS) molecular sequence homology with Aspergillus species from the section Restricti. The strain was cultivated 9 days on potato dextrose broth (PDB), and the medium evaluated as antioxidant on primary normal human dermal fibroblasts (NHDF). The cultivation broth was submitted to sterile filtration, lyophilized and used without any further processing to give the Aspergillus chevalieri TM2-S6 cultivation broth ingredient named ACBB. ACCB contains two main compounds: tetrahydroauroglaucin and flavoglaucin. Under oxidative stress, ACCB showed a significant promotion of cell viability. To elucidate the mechanism of action, the impact on a panel of hundreds of genes involved in fibroblast physiology was evaluated. Thus, ACCB stimulates cell proliferation (VEGFA, TGFB3), antioxidant response (GPX1, SOD1, NRF2), and extracellular matrix organization (COL1A1, COL3A1, CD44, MMP14). ACCD also reduced aging (SIRT1, SIRT2, FOXO3). These findings indicate that Aspergillus chevalieri TM2-S6 cultivation broth exhibits significant in vitro skin protection of human fibroblasts under oxidative stress, making it a potential cosmetic ingredient.

Honey Extracts Exhibit Cytoprotective Properties against UVB-Induced Photodamage in Human Experimental Skin Models.

In the present study, we aimed to examine the antioxidant, antiaging and photoprotective properties of Greek honey samples of various botanical and geographical origin. Ethyl-acetate extracts were used and the and the total phenolic/flavonoid content and antioxidant capacity were evaluated. Honey extracts were then studied for their cytoprotective properties against UVB-induced photodamage using human immortalized keratinocytes (HaCaT) and/or reconstituted human skin tissue models. Specifically, the cytotoxicity, oxidative status, DNA damage and gene expression levels of specific matrix metalloproteinases (MMPs) were examined. Overall, the treatment of HaCaT cells with honey extracts resulted in lower levels of DNA strand breaks and attenuated the decrease in cell viability following UVB exposure. Additionally, honey extracts significantly decreased the total protein carbonyl content of the irradiated cells, however, they had no significant effect on their total antioxidant status. Finally, the extracts alleviated the UVB-induced up-regulation of MMPs-3, -7 and -9 in a model of reconstituted skin tissue. In conclusion, honey extracts exhibited significant photoprotective and antiaging properties under UVB exposure conditions and thus could be further exploited as promising agents for developing novel and naturally-based, antiaging cosmeceutical products.

Transcriptional and epigenetic effects of Vitis vinifera L. leaf extract on UV-stressed human dermal fibroblasts.

Adverse environmental conditions such as UV radiation induce oxidative and aging events leading to severe damage to human skin cells. Natural products such as plant extracts have been implicated in the skin anti-oxidant and anti-aging cellular protection against environmental stress. Moreover, environmental factors have been shown to impact chromatin structure leading to altered gene expression programs with profound changes in cellular functions. In this study, we assessed the in vitro effect of a leaf extract from Vitis vinifera L. on UV-stressed primary human dermal fibroblasts, focusing on gene expression and DNA methylation as an epigenetic factor. Expression analysis of two genes known to be implicated in skin anti-aging, SIRT1and HSP4, demonstrated significant induction in the presence of the extract under normal or UVA conditions. In addition, DNA methylation profiling of SIRT1 and HSP47 promoters showed that the V. vinifera L. extract induced changes in the DNA methylation pattern of both genes that may be associated with SIRT1 and HSP47 gene expression. Our study shows for the first time transcriptional and DNA methylation alterations on human skin fibroblasts exposed to UV stress and suggest a protective effect of a V. vinifera extract possibly through transcriptional regulation of critical skin anti-aging genes.

Antioxidant Profiles of Vitis vinifera L. and Salvia triloba L. Leaves Using High-Energy Extraction Methodologies.

The profiles of Vitis vinifera L. and Salvia triloba L. leaf extracts have been studied via photometric assays on the basis of their total phenolic and flavonoid content as well as of their radical scavenging and antioxidant activities. Ultrasound-assisted (UAE) and pressurized liquid extractions (PLE) were implemented for producing polar fractions from the plants, using different methanol-water and glycerol-water mixtures for UAE and PLE, respectively. Aqueous methanol was proved an effective solvent for the UAE of total phenolics and flavonoids as well as for increased radical scavenging and antioxidant activities. As for PLE, plain water was proved a more efficient solvent than hydroglycerolic mixtures. Overall, irrespective of the solvent(s) used, UAE extracts showed higher values compared with the PLE extracts for all the photometric determinations and for both plant species. Moreover, Salvia UAE and PLE extracts presented higher total phenolic and flavonoid contents, accompanied by higher radical scavenging and antioxidant activities, compared with Vitis extracts. The correlations among photometric results were also studied, indicating the categories of compounds that relate to the antioxidant and/or radical scavenging activities of the extracts. Mixtures of the examined extracts could be exploited as the basis of novel phytotherapeutic products in the cosmetic sector.

Genomic and phylogenetic analysis of choriolysins, and biological activity of hatching liquid in the flatfish Senegalese sole.

The hatching enzymes or choriolysins are key proteases in fish life cycle controlling the release of larvae to surrounding environment that have been suggested as target for novel biotechnological uses. Due to the large amounts of eggs released by the flatfish Solea senegalensis, during the spawning season, the hatching liquid properties and choriolysin-encoding genes were investigated in this species. A genomic analysis identified four putative genes referred to as SseHCEa, SseHCEb, SseLCE and SseHE. The phylogenetic analysis classified these paralogs into two clades, the clade I containing SseHCE paralogs and the clade II containing two well-supported subclades named as HE and LCE. The two SseHCE paralogs were intron-less and both genes were tandemly arrayed very close in the genome. The synteny and gene rearrangement identified in the flatfish lineage indicated that the duplication of these two paralogs occurred recently and they are under divergent evolution. The genes SseHE and SseLCE were structured in 8 exons and 7 introns and the synteny was conserved in teleosts. Expression studies confirmed that the four genes were expressed in the hatching gland cells and they migrate co-ordinately from the head to around the yolk sac close to the hatch with specific temporal and intensity expression profiles. Although the mRNA levels of the four genes peaked in the hours previous to larval hatching, the SseHCE and SseLCE paralogs kept a longer expression than SseHE after hatching. These expression patterns were consistent even when larvae were incubated at different temperatures that modified hatching times. The analysis of hatching-liquid using SDS-PAGE and zymography analyses of hatching liquid identified a major band of expected choriolysin size. The optimal pH for protease activity was 8.5 and inhibition assays using EDTA demonstrated that most of the activity in the hatching liquid was due to metalloproteases with Ca2+ ions acting as the most effective metal to restore the activity. All these data provide new clues about the choriolysin evolution and function in flatfish with impact in the aquaculture and the blue cosmetic industry.

Propolis Extracts Inhibit UV-Induced Photodamage in Human Experimental In Vitro Skin Models.

The aim of this study was to assess the antioxidant, photoprotective, and antiaging effects of Greek propolis. Propolis was subjected to n-heptane or methanol extraction. Total phenolic/flavonoid content and antioxidant potential were determined in the extracts. Promising extracts were evaluated for their cytoprotective properties using human immortalized keratinocyte (HaCaT) or reconstituted human skin tissue following exposure to UVB. Assessment of cytotoxicity, DNA damage, oxidative status, and gene/protein expression levels of various matrix metalloproteinases (MMPs) were performed. The propolis methanolic fractions exhibited higher total phenolic and flavonoid contents and significant in vitro antioxidant activity. Incubation of HaCaT cells with certain methanolic extracts significantly decreased the formation of DNA strand breaks following exposure to UVB and attenuated UVB-induced decrease in cell viability. The extracts had no remarkable effect on the total antioxidant status, but significantly lowered total protein carbonyl content used as a marker for protein oxidation in HaCaT cells. MMP-1, -3, -7, and -9, monitored as endpoints of antiaging efficacy, were significantly reduced by propolis following UVB exposure in a model of reconstituted skin tissue. In conclusion, propolis protects against the oxidative and photodamaging effects of UVB and could be further explored as a promising agent for developing natural antiaging strategies.

Photometric Analysis of Propolis from the Island of Samothraki, Greece. The Discovery of Red Propolis.

Propolis presents notable and variable antioxidant activity depending on the territory and the local flora. As a result, propolis collected from areas presenting botanical diversity can become an intriguing research field. In the present study, we examined propolis from different areas of Samothraki, a small Greek island in the north-eastern Aegean Sea, considered a hot-spot of plant biodiversity. The analysis of propolis samples presented huge variability in the antioxidant activity, the total polyphenol content and the total flavonoids content. Propolis from two areas presented high antioxidant activity with a maximum at 1741.48 µmol of Trolox equivalents per gram of dry propolis weight, very high polyphenol content, 378.73 mg of gallic acid equivalents per gram of dry propolis weight, and high flavonoid content with a maximum concentration of 70.31 mg of quercetin equivalents per gram of dry propolis weight. The samples that presented the best qualitative characteristics were all red propolis which is a type that has never been reported in any part of Europe.

Physicochemical characterization of sterilized muds for pharmaceutics/cosmetics applications.

Clays and muds have been used for centuries as cosmetics or pharmaceutical products for various therapies. The suitability of muds and clays for health- and beauty-related applications depends on their physicochemical properties, mineralogical composition, particle characteristics and toxicity. In this work, the physicochemical characterization of 12 mud specimens from different natural spa resorts in Greece and one from Israel (Dead Sea) is presented. All specimens were sterilized at 121 °C for 20 min, because of their intended use. The Greek mud specimens were collected from various locations in Macedonia, Western Greece and Northeast Aegean. All muds were characterized concerning their mineralogical, chemical components as well as their morphological characteristics using appropriate methods [powder X-ray diffraction (XRD), thermogravimetric analysis (TGA), nitrogen absorption specific surface area measurements (BET), scanning electron microscopy and energy dispersive X-ray spectroscopy]. The concentrations of F-, Cl-, NO3- and SO42- anions at equilibrium with the mud specimens were measured by ion chromatography. Total calcium concentration was measured using atomic absorption spectroscopy, and the concentration of total N, C, H and S in the solids was measured using elemental analysis. Moreover, total phenolic concentration (TPC) in distilled water equilibrated with the mud specimens was measured as an index for their antioxidant properties. Several muds were found to present high TPC. Several of the examined mud specimens were found to have the potential use as pharmaceuticals or cosmetics. Based on the physicochemical characteristics of the mud specimens examined, possible improvement in their use and applicability has been suggested.

Biological properties of mud extracts derived from various spa resorts.

Spa resorts are known for thousands of years for their healing properties and have been empirically used for the treatment of many inflammatory conditions. Mud is one of the most often used natural materials for preventive, healing and cosmetic reasons and although it has been used since the antiquity, little light has been shed on its physical, chemical and biological properties. In this study we examined the effect of mud extracts on the expression of adhesion molecules (CAMs) by endothelial cells as well as their effects on monocyte adhesion to activated endothelial cells. Most of mud extracts inhibited the expression of VCAM-1 by endothelial cells and reduced monocyte adhesion to activated endothelial cells, indicating a potent anti-inflammatory activity. Furthermore, the mud extracts were tested for their antimicrobial activity; however, most of them appeared inactive against S. aureus and S. epidermidis. One of the mud extracts (showing the best stabilization features) increased significantly the expression of genes involved in cell protection, longevity and hydration of human keratinocytes, such as, collagen 6A1, forkhead box O3, sirtuin-1, superoxide dismutase 1 and aquaporin-3. The present study reveals that mud exerts important beneficial effects including anti-inflammatory and anti-aging activity as well as moisturizing effects, implicating important cosmeceutical applications.

Microbial biosensors to monitor the encapsulation effectiveness of Doxorubicin in chimeric advanced Drug Delivery Nano Systems: A calorimetric approach.

The release of the anticancer drug doxorubicin (DOX) incorporated in a new drug carrier, namely a chimeric nanosystem formed by liposomes and dendrimers, was studied following the influence of the drug on the growth kinetics of the Lactobacillus helveticus bacterium, that would mimic the intestinal microflora. The bacterial growth was followed at 37°C by means of Isothermal Titration Calorimetry (ITC) and the method was assessed to monitor the overall effect of the delivered drug obtaining simple objective parameters to define the encapsulation effectiveness of the system, discriminating dose effects even in cases of very low release. Traditional microbiological investigations and in vitro release tests were also performed in parallel for validation. The achieved results suggest that L. helveticus is an excellent candidate as biosensor to assess the sealing effectiveness of these DOX drug carriers through ITC investigations. This approach can be extended for quantitative comparison of drug delivery systems with the same drug inserted in other supramolecular bodies for quantitative comparison. The peculiar results for the DOX drug carrier system investigated, indicate also that, the use of hydrophilic dendrimers in this case, produce a high sealing effect that seems promising in terms of the intestinal flora protection.