The nutraceutical value of carnitine and its use in dietary supplements

Carnitine can be considered a conditionally essential nutrient for its importance in human physiology. This paper provides an updated picture of the main features of carnitine outlining its interest and possible use. Particular attention has been addressed to its beneficial properties, exploiting carnitine’s properties and possible use by considering the main in vitro, in animal, and human studies. Moreover, the main aspects of carnitine-based dietary supplements have been indicated and defined with reference to their possible beneficial health properties.The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007. E. B. Souto acknowledges the sponsorship of the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), A.M.S. the UID/AGR/04033/2019 (CITAB), receiving support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Sucupira oil-loaded nanostructured lipid carriers (NLC): lipid screening, factorial design, release profile, and cytotoxicity

Essential oils are odorant liquid oily products consisting of a complex mixture of volatile compounds obtained from a plant raw material. They have been increasingly proven to act as potential natural agents in the treatment of several human conditions, including diabetes mellitus (DM). DM is a metabolic disorder characterized by chronic hyperglycemia closely related to carbohydrate, protein and fat metabolism disturbances. In order to explore novel approaches for the management of DM our group proposes the encapsulation of sucupira essential oil, obtained from the fruits of the Brazilian plants of the genus Pterodon, in nanostructured lipid carriers (NLCs), a second generation of lipid nanoparticles which act as new controlled drug delivery system (DDS). Encapsulation was performed by hot high-pressure homogenization (HPH) technique and the samples were then analyzed by dynamic light scattering (DLS) for mean average size and polydispersity index (PI) and by electrophoretic light scattering (ELS) for zeta potential (ZP), immediately after production and after 24 h of storage at 4 °C. An optimal sucupira-loaded NLC was found to consist of 0.5% (m/V) sucupira oil, 4.5% (m/V) of Kollivax® GMS II and 1.425% (m/V) of TPGS (formulation no. 6) characterized by a mean particle size ranging from 148.1 ± 0.9815 nm (0 h) to 159.3 ± 9.539 nm (at 24 h), a PI from 0.274 ± 0.029 (0 h) to 0.305 ± 0.028 (24 h) and a ZP from −0.00236 ± 0.147 mV (at 0 h) to 0.125 ± 0.162 (at 24 h). The encapsulation efficiency and loading capacity were 99.98% and 9.6%, respectively. The optimized formulation followed a modified release profile fitting the first order kinetics, over a period of 8 h. In vitro cytotoxicity studies were performed against Caco-2 cell lines, for which the cell viability above 90% confirmed the non-cytotoxic profile of both blank and sucupira oil-loaded NLC.This work was financed through the projects M-ERA-NET/0004/2015-PAIRED, UIDB/04469/2020 (CEB strategic fund) and PEst-OE/UID/AGR/04033/2019 (CITAB strategic fund), receiving financial support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER, under the Partnership Agreement PT2020. The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio

Multiple cell signalling pathways of human proinsulin c-peptide in vasculopathy protection

A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic -cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive -cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signalregulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works highlight the role of C-peptide in the prevention and amelioration of diabetes and also in organ-specific complications. Benefits of C-peptide in microangiopathy and vasculopathy have been shown through conservation of vascular function, and also in the prevention of endothelial cell death, microvascular permeability, neointima formation, and in vascular inflammation. Improvement of microvascular blood flow by replacing a physiological amount of C-peptide, in several tissues of diabetic animals and humans, mainly in nerve tissue, myocardium, skeletal muscle, and kidney has been described. A review of the multiple cell signalling pathways of human proinsulin C-peptide in vasculopathy protection is proposed, where the approaches to move beyond the state of the art in the development of innovative and effective therapeutic options of diabetic neuropathy and nephropathy are discussed.The authors acknowledge the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project references M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020. The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio

Astragalus (Astragalus membranaceus Bunge): botanical, geographical, and historical aspects to pharmaceutical components and beneficial role

Medicinal plants always are part of folk medicine and are nowadays receiving worldwide attention for prophylaxis, management, and treatment of several diseases, as an alternative to chemical drugs. The current work provided a comprehensive overview and analysis of the Astragalus and health relationship in literature. The analysis of their therapeutic potential is thus instrumental to understand their bioactivity. Among these, the flowering medicinal plant Astragalus membranaceus has raised interest due to several beneficial health effects. This perspective review discussed the botanical, geographical, historical, and the therapeutic properties of A. membranaceus, with a special focus on its health improving effects and medicinal applications both in vitro and in vivo.Funding provided by Università degli Studi di Napoli Federico II within the CRUI-CARE Agreementinfo:eu-repo/semantics/publishedVersio

Vitex agnus-castus L.: main features and nutraceutical perspectives

Medicinal plants are used worldwide due to their lower risk of side effects and eco-friendly, cost-effective production when compared to chemical drugs, encouraging researchers to further exploit the therapeutic potential of the former. One of the most popular medicinal plants is Vitex agnus-castus L., grown in tropical and sub-tropical regions, to which different health benefits have already been attributed. In this perspective article, the in vitro and in vivo therapeutic properties of V. agnus-castus L. have been analyzed and reviewed with a special focus on its health-promoting effects and potential nutraceutical applications.The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007. E.B.S. acknowledges the sponsorship of the projects M-ERA-NET-0004/2015-PAIRED and UIDB/04469/2020 (strategic fund); A.M.S. acknowledges UIDB/04033/2020 (CITAB), receiving support from the Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT/MEC) through national funds, and co-financed by FEDER under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Carboxymethyl cellulose as a food emulsifier: are its days numbered?

Carboxymethyl cellulose use in industry is ubiquitous. Though it is recognized as safe by the EFSA and FDA, newer works have raised concerns related to its safety, as in vivo studies showed evidence of gut dysbiosis associated with CMC’s presence. Herein lies the question, is CMC a gut pro-inflammatory compound? As no work addressed this question, we sought to understand whether CMC was pro-inflammatory through the immunomodulation of GI tract epithelial cells. The results showed that while CMC was not cytotoxic up to 25 mg/mL towards Caco-2, HT29-MTX and Hep G2 cells, it had an overall pro-inflammatory behavior. In a Caco-2 monolayer, CMC by itself increased IL-6, IL-8 and TNF-α secretion, with the latter increasing by 1924%, and with these increases being 9.7 times superior to the one obtained for the IL-1β pro-inflammation control. In co-culture models, an increase in secretion in the apical side, particularly for IL-6 (692% increase), was observed, and when RAW 264.7 was added, data showed a more complex scenario as stimulation of pro-inflammatory (IL-6, MCP-1 and TNF-α) and anti-inflammatory (IL-10 and IFN-β) cytokines in the basal side was observed. Considering these results, CMC may exert a pro-inflammatory effect in the intestinal lumen, and despite more studies being required, the incorporation of CMC in foodstuffs must be carefully considered in the future to minimize potential GI tract dysbiosis.info:eu-repo/semantics/publishedVersio

Ocular cell lines and genotoxicity assessment

Genotoxicity screening tests aim to evaluate if and to what extent a compound in contact with the human body (e.g., a drug molecule, a compound from the environment) interacts with DNA. The comet assay is a sensitive method used to predict the risk of DNA damage in individual cells, as it quantifies the tape breaks, being the alkaline version (pH > 13) the most commonly used in the laboratory. Epithelial cells serve as biomatrices in genotoxicity assessments. As ca. 80% of solid cancers are of epithelial origin, the quantification of the DNA damage upon exposure of epithelial cells to a drug or drug formulation becomes relevant. Comet assays run in epithelial cells also have clinical applications in human biomonitoring, which assesses whether and to what extent is the human body exposed to environmental genotoxic compounds and how such exposure changes over time. Ocular mucosa is particularly exposed to environmental assaults. This review summarizes the published data on the genotoxicity assessment in estimating DNA damage in epithelial cells with a special focus on ocular cell lines. General comet assay procedures for ex vivo and in vivo epithelium samples are also described.The authors acknowledge the financial support received from the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the projects M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020. The FCT Grant to CMG (SFRH/BD/145855/2019) and project PEst-OE/UID/AGR/04033/2019 (CITAB strategic fund) are also acknowledged.info:eu-repo/semantics/publishedVersio

Nanomaterials for skin delivery of cosmeceuticals and pharmaceuticals

Featured Application: The loading of pharmaceuticals and cosmeceuticals into nanomaterials is discussed as new formulations for potential treatment of age-related skin problems. Topical administration of active ingredients formulated as nanopharmaceuticals and nanonutraceuticals is discussed.Abstract: Skin aging is described as dermatologic changes either naturally occurring over the course of years or as the result of the exposure to environmental factors (e.g., chemical products, pollution, infrared and ultraviolet radiations). The production of collagen and elastin, the main structural proteins responsible for skin strength and elasticity, is reduced during aging, while their role in skin rejuvenation can trigger a wrinkle reversing effect. Elasticity loss, wrinkles, dry skin, and thinning are some of the signs that can be associated with skin aging. To overcome skin aging, many strategies using natural and synthetic ingredients are being developed aiming to reduce the signs of aging and/or to treat age-related skin problems (e.g., spots, hyper- or hypopigmentation). Among the different approaches in tissue regeneration, the use of nanomaterials loaded with cosmeceuticals (e.g., phytochemicals, vitamins, hyaluronic acid, and growth factors) has become an interesting alternative. Based on their bioactivities and using different nanoformulations as efficient delivery systems, several cosmeceutical and pharmaceutical products are now available on the market aiming to mitigate the signs of aged skin. This manuscript discusses the state of the art of nanomaterials commonly used for topical administration of active ingredients formulated in nanopharmaceuticals and nanocosmeceuticals for skin anti-aging.The authors acknowledge the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the projects M-ERANET/0004/2015-PAIRED and UIDB/04469/2020 (strategic fund) co-financed by FEDER, under the Partnership Agreement PT2020. The FCT grant to CMG (SFRH/BD/145855/2019) and project PEst-OE/UID/AGR/04033/2019 (CITAB strategic fund) are also acknowledged. The authors acknowledge the support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio

Uncaria tomentosa (Willd. ex Schult.): Focus on Nutraceutical Aspects

Medicinal plants have been globally exploiting as an alternative to chemical drugs in the treatment of several diseases due to low unwanted side effects, environmentally friendly nature, and low production costs. Therefore, it is important to analyze the therapeutic properties of various medicinal plants to understand their potential bioactivity. Uncaria tomentosa is one of these medicinal plants with many health-promoting effects. Although the geographical resources of cat's claw go back to the remote tropics of the Amazon, industrialized countries use the plant extensively in trade. Various parts of the plants such as flowers, leaves, Stem, hooks, and seeds are mainly used medicinally to treat inflammation, asthma, allergies, skin impurities, microbial infections, neurodegenerative diseases, cancer, cirrhosis, gastrointestinal disorders, arthritis, heart disease, rheumatism, and fever. The endpoint of this review article is to prospectively scrutinize in vitro and in vivo the therapeutic potential of this plant, especially in terms of its nutritional applications and healthbeneficial effects. © 2022 Bentham Science Publishers.(undefined)info:eu-repo/semantics/publishedVersio

Nanopharmaceutics: Part II - Production scales and clinically compliant production methods

Due the implementation of nanotechnologies in the pharmaceutical industry over the last few decades, new type of cutting-edge formulationsnanopharmaceuticshave been proposed. These comprise pharmaceutical products at the nanoscale, developed from different types of materials with the purpose to, e.g., overcome solubility problems of poorly water-soluble drugs, the pharmacokinetic and pharmacodynamic profiles of known drugs but also of new biomolecules, to modify the release profile of loaded compounds, or to decrease the risk of toxicity by providing site-specific delivery reducing the systemic distribution and thus adverse side effects. To succeed with the development of a nanopharmaceutical formulation, it is first necessary to analyze the type of drug which is to be encapsulated, select the type matrix to load it (e.g., polymers, lipids, polysaccharides, proteins, metals), followed by the production procedure. Together these elements have to be compatible with the administration route. To be launched onto the market, the selected production method has to be scaled-up, and quality assurance implemented for the product to reach clinical trials, during which in vivo performance is evaluated. Regulatory issues concerning nanopharmaceutics still require expertise for harmonizing legislation and a clear understanding of clinically compliant production methods. The first part of this study addressing Nanopharmaceutics: Part IClinical trials legislation and Good Manufacturing Practices (GMP) of nanotherapeutics in the EU has been published in Pharmaceutics. This second part complements the study with the discussion about the production scales and clinically compliant production methods of nanopharmaceutics.The financial support was received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the projects M‐ERA‐NET‐0004/2015‐PAIRED and UIDB/04469/2020 (strategic fund), co‐financed by FEDER, under the Partnership Agreement PT2020. Authors thank the support of the project: Nutraceutica come supporto nutrizionale nel paziente oncologico; CUP: B83D18000140007.info:eu-repo/semantics/publishedVersio