Crucial Challenges in the Development of Green Extraction Technologies to Obtain Antioxidant Bioactive Compounds from Agro-industrial By–products

Exploitation of agro-industrial by-products represents an important source of bioactive compounds that can be used both directly as ingredients and for the production of functional ingredients. Among these compounds, polyphenols are capable of strengthening endogenous antioxidant defences in human tissues, preventing cardiovascular and neurodegenerative diseases. The present paper aims to evaluate and review various green extraction technologies for a cheap, fast, eco-friendly procedure to obtain these bioactive molecules. Several physicochemical approaches can be used with the aim of optimizing the use of energy, solvents, and pressure; among them are ultrasound-assisted extraction, subcritical and supercritical fluid extraction, extraction with neoteric solvents (ionic liquids, deep eutectic solvents, and natural deep eutectic solvents), microwave-assisted extraction, pressurized liquid extraction, pulsed electric field, multi-frequency multimode modulated technology, rapid solid liquid dynamic extraction, and enzyme-assisted extraction. The challenges and future work regarding the development of these green products for the commercial markets were comprehensively evaluated. This work is licensed under a Creative Commons Attribution 4.0 International License

Analysis of polyphenolic composition and stability of magistral preparation based on salviae officinalis folium

A magistral preparation based on the sage leaf decoction or infusion is one of the most popular herbal prescriptions prepared in pharmacies in Lower Silesia (Poland) for gargling in the case of pharyngitis or mouth infections. Other components of this preparation are boric acid, aluminum(III) acetotartrate or Burow's solution, and glycerol. The study aimed to investigate the polyphenolic composition and relations between herbal and chemical ingredients that are present in this mixture in comparison with the traditional aqueous galenic forms - infusion and decoction. The analysis was performed using high-performance liquid chromatography with diode-array detector (HPLC-DAD) and electrospray ionization mass spectrometry (ESI-MS) methods. The main polyphenolic ingredients of sage leaf were rosmarinic acid (RA) and luteolin 7-O-β-glucuronide. The RA predominance was observed in the infusion, decoction and magistral preparation. Comparing the contents of analyzed polyphenols, it was confirmed that their levels in the decoction were higher than in the infusion. Thus, the pharmacological activity of the examined magistral preparation results from the presence of boric acid, aluminum(III) salts and polyphenolic components of sage leaf hot water extract. The succeeding study showed that in the presence of excess salts of aluminum(III) and boric acid, sage polyphenols are partially soluble in an aqueous medium (mainly phenolic acids) and complexed as precipitated sediment (especially flavonoids). The aqueous solutions of this preparation obtained according to the recommendation are cloudy, which suggests limited solubility of the formed complexes. Therefore, the therapeutic activity should be associated with the presence of water-soluble caffeic acid esters like rosmarinic acid. The influence of luteolin glycosides coordination complexes is not evident. The obtained results also confirm the stability of the examined prescription formulation in the conditions of cold storage (4-6OC) within 7 days from its production

Investigation into Polyphenol Profile and Biological Activities of Enriched Persimmon/Apple Smoothies during Storage

Smoothies are becoming an increasingly popular product as a healthy alternative to snacks. The consumer expects from this product that, apart from its nutritional value, it will also be qualitatively stable during storage. Therefore, in this study, original smoothies obtained with persimmon fruit puree and apple juice (Dk/Md) enriched with Arbutus unedo fruits, Myrtus communis purple berry extract, Acca sellowiana, and Crocus sativus petal juice were evaluated for their polyphenol composition, antioxidant activity, and inhibition on targeted digestive enzymes, over six months of storage. The amount of polyphenols evaluated by UPLC-PDA analysis decreased in six months from 23.5% for both Dk/Md and enriched C. sativus smoothies to 42.5% for enriched A. sellowiana, with anthocyanins the most sensitive compounds (71.7–100% loss). Values of antioxidant assays generally strongly decreased during the first three months (up to ca. 60%) and to a lesser extent in the following three months (0.4–27%). In addition, inhibitory activity on α-amylase, α-glucosidase, and pancreatic lipase, especially on the last two enzymes, was negatively affected by time storage. The outcome of this study indicates that persimmon fruit is a good option for producing smoothies, and enrichment with other plant extracts can enhance the bioactive compound content and biological activities. It is recommended that appropriate storage strategies to preserve the properties of those smoothies should be developed

Euphorbia characias Extract: Inhibition of Skin Aging-Related Enzymes and Nanoformulation

Plant extracts have long served as important sources of bioactive compounds, and they are currently the focus of extensive research in the development of novel preventive and therapeutic strategies. However, their health benefits are often limited by low bioavailability. Nanoparticle delivery systems can represent a solution to such limitations. Euphorbia characias is a Mediterranean shrub known to have biological activities, such as inhibiting tyrosinase and showing a potential role as a skin-whitening agent. In this study, an ethanolic extract from E. characias leaves was tested for its inhibitory activity on skin-related enzymes, such as elastase, collagenase, and hyaluronidase, and for sun protection factors. Moreover, the extract was formulated in phospholipid vesicles to improve its local bioavailability and applicability. The vesicles were characterized by size, surface charge, storage stability, and entrapment efficiency. The nanoformulation was also evaluated for antioxidant activity and assayed for cytocompatibility and anti-tyrosinase activity in melanoma cells. Our findings demonstrated that the extract has a photo-protective effect and enzyme-inhibitory properties. E. characias nanoformulation was also cytocompatible and improved the extract’s activity in the cells, suggesting a potential skin application for antimelanogenic treatments and confirming the key role of nanotechnological approaches to maximize plant extract’s potentialities

Ceratonia siliqua L. Pod Extract: From Phytochemical Characterization to Liposomal Formulation and Evaluation of Behaviour in Cells

The formulation of plant extracts in phospholipid vesicles is a promising strategy to exploit their biological properties while solving problems related to poor solubility in water, high instability, and low skin permeation and retention time. In this study, Ceratonia siliqua ripe pods were used for the preparation of a hydro-ethanolic extract, which showed antioxidant properties owing to the presence of biologically active compounds identified by liquid chromatography–mass spectrometry (e.g., hydroxybenzoic acid and flavonoid derivatives). To improve the applicability of the extract in therapy, a topical formulation based on liposomes was explored. The vesicles were characterized by small size (around 100 nm), negative charge (−13 mV), and high entrapment efficiency (>90%). Furthermore, they displayed both spherical and elongated shapes, with oligolamellar structure. Their biocompatibility was demonstrated in cells, including erythrocytes and representative skin cell lines. The antioxidant activity of the extract was proved by the scavenging of free radicals, the reduction of ferric ions, and the protection of skin cells from oxidative damage

Phenolic Fingerprint, Bioactivity and Nanoformulation of Prunus spinosa L. Fruit Extract for Skin Delivery

The nanoformulation of plant extracts in phospholipid vesicles is a promising strategy to exploit the biological properties of natural bioactive substances and overcome drawbacks such as poor aqueous solubility, chemical instability, low skin permeation and retention time, which strongly limit their topical application. In this study, Prunus spinosa berries were used for the preparation of a hydro-ethanolic extract, which showed antioxidant and antibacterial properties owing to the presence of phenolic compounds. Two types of phospholipid vesicles were developed to improve the applicability as topical formulations. Liposomes and Penetration Enhancer-containing Vesicles were characterized for mean diameter, polydispersity, surface charge, shape, lamellarity, and entrapment efficiency. Additionally, their safety was assayed with different cell models, including erythrocytes and representative skin cell lines

Combining Different Approaches for Grape Pomace Valorization: Polyphenols Extraction and Composting of the Exhausted Biomass

Grape pomace represents 60%, by weight, of the solid side-streams of the wine-making process. The quantities produced, seasonality, and the presence of polyphenols pose economic and environmental issues that require proper management approaches based on the principles of sustainability and circular economy. The present work focuses on the combined application of solid-liquid extraction of polyphenols from ground grape pomace using a hydroethanolic mixture and the composting of the exhausted pomace. The obtained results support the possibility of recovering approximately 76.5 g of extract per kg of dry grape pomace (or 1.8 g of total phenols per kg of dry grape pomace). The composting process was not affected by the extraction process. On the contrary, the composting process was enhanced by the pomace particle size reduction, in terms of final biostability and content of humic acids

Nanotechnology for natural medicine: Formulation of neem oil loaded phospholipid vesicles modified with argan oil as a strategy to protect the skin from oxidative stress and promote wound healing

Neem oil, a plant-derived product rich in bioactives, has been incorporated in liposomes and hyalurosomes modified by adding argan oil and so called argan-liposomes and argan-hyaluro-somes. Argan oil has also been added to the vesicles because of its regenerative and protective effects on skin. In the light of this, vesicles were specifically tailored to protect the skin from oxidative stress and treat lesions. Argan-liposomes were the smallest vesicles (~113 nm); the addition of sodium hyaluronate led to an increase in vesicle size (~143 nm) but it significantly improved vesicle stability during storage. In vitro studies confirmed the free radical scavenging activity of formula-tions, irrespective of their composition. Moreover, rheological investigation confirmed the higher viscosity of argan-hyalurosomes, which avoid formulation leakage after application. In vitro studies performed by using the most representative cells of the skin (i.e., keratinocytes and fibroblasts) un-derlined the ability of vesicles, especially argan-liposomes and argan-hyalurosomes, to counteract ox-idative stress induced in these cells by using hydrogen peroxide and to improve the proliferation and migration of cells ensuring the more rapid and even complete closure of the wound (scratch assay)

Lactic acid fermentation as a tool to enhance the antioxidant properties of Myrtus communis berries

Background: Myrtle (Myrtus communis L.) is a medicinal and aromatic plant belonging to Myrtaceae family, which is largely diffused in the Mediterranean areas and mainly cultivated in Tunisia and Italy. To the best of our knowledge, no studies have already considered the use of the lactic acid fermentation to enhance the functional features of M. communis. This study aimed at using a selected lactic acid bacterium for increasing the antioxidant features of myrtle berries, with the perspective of producing a functional ingredient, dietary supplement or pharmaceutical preparation. The antioxidant activity was preliminarily evaluated through in vitro assays, further confirmed through ex vivo analysis on murine fibroblasts, and the profile of phenol compounds was characterized. Results: Myrtle berries homogenate, containing yeast extract (0.4%, wt/vol), was fermented with Lactobacillus plantarum C2, previously selected from plant matrix. Chemically acidified homogenate, without bacterial inoculum and incubated under the same conditions, was used as the control. Compared to the control, fermented myrtle homogenate exhibited a marked antioxidant activity in vitro. The radical scavenging activity towards DPPH increased by 30%, and the inhibition of linoleic acid peroxidation was twice. The increased antioxidant activity was confirmed using Balb 3 T3 mouse fibroblasts, after inducing oxidative stress, and determining cell viability and radical scavenging activity through MTT and DCFH-DA assays, respectively. The lactic acid fermentation allowed increased concentrations of total phenols, flavonoids and anthocyanins, which were 5–10 times higher than those found for the non-fermented and chemically acidified control. As shown by HPLC analysis, the main increases were found for gallic and ellagic acids, and flavonols (myricetin and quercetin). The release of these antioxidant compounds would be strictly related to the esterase activities of L. plantarum. Conclusions: The lactic acid fermentation of myrtle berries is a suitable tool for novel applications as functional food dietary supplements or pharmaceutical preparations