Plant phenolics: extraction, analysis and their antioxidant and anticancer properties

Phenolics are broadly distributed in the plant kingdom and are the most abundant secondary metabolites of plants. Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of various oxidative stress associated diseases such as cancer. In the last few years, the identification and development of phenolic compounds or extracts from different plants has become a major area of health- and medical-related research. This review provides an updated and comprehensive overview on phenolic extraction, purification, analysis and quantification as well as their antioxidant properties. Furthermore, the anticancer effects of phenolics in-vitro and in-vivo animal models are viewed, including recent human intervention studies. Finally, possible mechanisms of action involving antioxidant and pro-oxidant activity as well as interference with cellular functions are discussed.     

Antioxidant activity and total phenolic content of aqueous and methanolic extracts of Jordanian plants: an ICBG project

As part of an International Cooperative Biodiversity Groups (ICBG) program to study Jordan's biodiversity, the relative levels of antioxidant activity and the total phenolic content of aqueous and methanolic extracts of a total of 95 plant species, all of Jordanian origin and those collected at random, have been measured. The total phenolic content of aqueous and methanolic extracts of the investigated plant species ranged from 4.4 to 78.3 mg and from 2.1 to 52.8 mg gallic acid equivalents g(-1) dry weight, respectively, while the total antioxidant capacity ranged from 20.0 to 916.7 and from 15.1 to 915.6 micromol Trolox equivalents g(-1) dry weight, respectively. Based on this collection, approximately 5% of assayed plants showed high levels of antioxidant activity. There was a significant linear correlation between antioxidant activity and total phenolic content for aqueous and methanolic extracts, suggesting that phenolic compounds were the predominant antioxidant components in the investigated plant species. Interestingly, a few of the collected plants had high-antioxidant activity yet "low" phenolic content includes Ceratonia siliqua and Viscum cruciatum. These plants may serve as sources of antioxidants with new chemotypes.     

Chemical composition of bioactive pressurized extracts of Romanian aromatic plants

In this contribution, pressurized liquid extraction (PLE) has been employed to isolate bioactive compounds from three native Romanian plants, oregano (Origanum vulgare), tarragon (Artemisia dracunculus) and wild thyme (Thymus serpyllum). Different PLE conditions have been tested including extraction with water, ethanol and their mixtures in a wide range of extraction temperatures (50-200°C), and the antioxidant capacity of the extracts was measured using different assays (DPPH radical scavenging, TEAC assay and Folin-Ciocalteau assay to measure total phenols). Moreover, a complete chemical characterization by using LC-MS/MS was carried out to be able to correlate the bioactivity with the particular chemical composition of each extract and plant. The use of PLE with water as a solvent at the highest temperature tested (200°C) always provided the highest extraction yields for the three studied plants, being maximum for oregano (>60%). Besides, oregano's pressurized water extracts at lower temperatures (50°C) presented the highest content on total phenols (184.9 mg gallic acid/g extract) and the best antioxidant activities (EC(50) 6.98 μg/ml). In general, oregano extracts were the most active, followed by wild thyme extracts. The antioxidant capacity measured by DPPH assay was highly correlated with the amount of total phenols. Moreover, the use of a LC-MS/MS method allowed the identification of 30 different phenolic compounds in the different extracts, including phenolic acids, flavones, flavanones and flavonols, which have an important influence on the total antioxidant capacity of the different extracts.     

Optimization strategy and validation of one chromatographic method as approach to determine the phenolic compounds from different sources

We have designed a novel working strategy to optimize a unique chromatographic method consisting of diode array detection for the analysis of the most representative phenolic compounds from different food sources. The simultaneous inclusion of standard phenolic compounds, phenolic compounds isolated from food sources and representative real extracts as an ultimate test in analysis has allowed to establish, for the first time, a unique liquid gradient to serve as an excellent medium for the investigation of phenolics in samples from different food sources. Under the optimized conditions, 21 commercially available phenolic compounds and 25 commercially unavailable phenolic structures were analyzed in less than 30 min. The chromatographic method was designed as an alternative for the provisional identification of these compounds before their full characterization. The optimized chromatographic method was carefully validated for precision and accuracy. A high reproducibility in the retention time (<2%), peak area and calibration slope (<5%) as well as recoveries higher than 95% were obtained in all cases. Consequently, the currently described method was successfully employed to study the phenolic compounds in the most representative food samples.     

Chemical characterization of leaves and calli extracts of Rosmarinus officinalis by UHPLC-MS

Rosmarinus officinalis L. (Lamiaceae) is an aromatic plant widely popular mainly due to its uses in traditional medicine as an anti-inflammatory, diuretic and antimicrobial, as well as in the prevention and treatment of diseases. These biological activities are mainly related to the presence of phenolic and terpenic compounds. This work reports a chemical profile analysis of extracts from leaves and calli of rosemary obtained by both pressurized liquid extraction and maceration. Chemical profiles were determined on calli extracts of 3, 6, 9, and 15 days of culture; chemical characterization and quantification of compounds was carried out using ultrahigh performance liquid chromatography-mass spectrometry. A total of 53 metabolites were identified in callus and 47 compounds in leaf extracts, of which 25 correspond to phenolic compounds, mainly flavonoids and flavones, 13 terpenes that include phenolic terpenes and one diterpenolactone, two glycosides which correspond to 6-O-caffeoyl-β-D-fructofuranosil-(2→1)-α-D-glucopyranoside and primulaverin, an aromatic compound identified as fenantrenone and a growth regulator 12-hydroxy jasmonic acid. These results showed that undifferentiated rosemary cells accumulate the same compounds identified mainly in highly specialized tissues such as leaves. The plant cell culture supply the possibility of developing biotechnological processes to obtain compounds of commercial interest.     

Cell Culture-Based Assessment of Toxicity and Therapeutics of Phytochemical Antioxidants

Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their effects have been linked to phytochemicals such as phenolic compounds and their antioxidant activities. The abundance and complexity of these bio-constituents highlight the need for well-defined in vitro characterization and quantification of the plant extracts/preparations that can translate to in vivo effects and hopefully to clinical use. This review article seeks to provide relevant information about the applicability of cell-based assays in assessing anti-cytotoxicity of phytochemicals considering several traditional and current methods.     

A Review of the Health Protective Effects of Phenolic Acids against a Range of Severe Pathologic Conditions (Including Coronavirus-Based Infections)

Phenolic acids comprise a class of phytochemical compounds that can be extracted from various plant sources and are well known for their antioxidant and anti-inflammatory properties. A few of the most common naturally occurring phenolic acids (i.e., caffeic, carnosic, ferulic, gallic, p-coumaric, rosmarinic, vanillic) have been identified as ingredients of edible botanicals (thyme, oregano, rosemary, sage, mint, etc.). Over the last decade, clinical research has focused on a number of in vitro (in human cells) and in vivo (animal) studies aimed at exploring the health protective effects of phenolic acids against the most severe human diseases. In this review paper, the authors first report on the main structural features of phenolic acids, their most important natural sources and their extraction techniques. Subsequently, the main target of this analysis is to provide an overview of the most recent clinical studies on phenolic acids that investigate their health effects against a range of severe pathologic conditions (e.g., cancer, cardiovascular diseases, hepatotoxicity, neurotoxicity, and viral infections—including coronaviruses-based ones).     

Screening of acetogenin-producing plants in Brazilian flora

The acetogenins are strongly bioactive natural compounds present in the bark, roots, leaves, and seeds of manyAnnonaceae plants. They are modified fatty acids and their cytotoxicities have been determined for different biological models including the in vitro growth inhibition of several human cancer cell lines. Very low acetogenin yield (< 0.1 g%) has been found previously in native phytobiomass, and we have now investigated the nonpredatory exploitation of the seeds as acetogenin sources characterizing the seed triacylglycerols (dominant fraction; > 90% of the whole lipid extracts) as potential valuable by-products.     

Potential Benefits of Black Chokeberry (Aronia melanocarpa) Fruits and Their Constituents in Improving Human Health

Aronia berry (black chokeberry) is a shrub native to North America, of which the fresh fruits are used in the food industry to produce different types of dietary products. The fruits of Aronia melanocarpa (Aronia berries) have been found to show multiple bioactivities potentially beneficial to human health, including antidiabetic, anti-infective, antineoplastic, antiobesity, and antioxidant activities, as well as heart-, liver-, and neuroprotective effects. Thus far, phenolic compounds, such as anthocyanins, cyanidins, phenolic acids, proanthocyanidins, triterpenoids, and their analogues have been identified as the major active components of Aronia berries. These natural products possess potent antioxidant activity, which contributes to the majority of the other bioactivities observed for Aronia berries. The chemical components and the potential pharmaceutical or health-promoting effects of Aronia berries have been summarized previously. The present review article focuses on the molecular targets of extracts of Aronia berries and the examples of promising lead compounds isolated from these berries, including cyanidin-3-O-galactoside, chlorogenic acid, quercetin, and ursolic acid. In addition, presented herein are clinical trial investigations for Aronia berries and their major components, including cancer clinical trials for chlorogenic acid and COVID-19 trial studies for quercetin. Additionally, the possible development of Aronia berries and their secondary metabolites as potential therapeutic agents is discussed. It is hoped that this contribution will help stimulate future investigations on Aronia berries for the continual improvement of human health.     

Recent Studies on Berry Bioactives and Their Health-Promoting Roles

Along with the increased knowledge about the positive health effects of food bioactives, the eating habits of many individuals have changed to obtain higher nutritional benefits from foods. Fruits are among the most preferred food materials in this regard. In particular, berry fruits are important sources in the diet in terms of their high nutritional content including vitamins, minerals, and phenolic compounds. Berry fruits have remedial effects on several diseases and these health-promoting impacts are associated with their phenolic compounds which may vary depending on the type and variety of the fruit coupled with other factors including climate, agricultural conditions, etc. Most of the berries have outstanding beneficial roles in many body systems of humans such as gastrointestinal, cardiovascular, immune, and nervous systems. Furthermore, they are effective on some metabolic disorders and several types of cancer. In this review, the health-promoting effects of bioactive compounds in berry fruits are presented and the most recent in vivo, in vitro, and clinical studies are discussed from a food science and nutrition point of view.     

Evaluation of the Antioxidant,Cytoprotective and Antityrosinase Effects of Schisandra chinensis Extracts and Their Applicability in Skin Care Product

Plant extracts have been widely used for skin care for many centuries, and nowadays, they are commonly applied for the development and enrichment of new cosmetic preparations. The present study aimed the assessment of the biological activity of aqueous Schisandra chinensis extracts as a potential ingredient of skin care products. The aspects studied involved the ability to neutralize free radicals, impact on viability and metabolism of keratinocytes, as well as tyrosinase inhibitory potential. Our study showed that aqueous S. chinensis extracts have a positive effect on keratinocyte growth and have high antioxidant potential and strong tyrosinase inhibitory activity. UPLC-MS analysis revealed that three groups of phenolic compounds were predominant in the analyzed extract, including lignans, phenolic acids and flavonoids and protocatechiuc and p-coumaryl quinic acids were predominant. Moreover, microwave-assisted extraction, followed by heat reflux extraction, was the most effective for extracting polyphenols. Furthermore, a prototypical natural body washes gel formulation containing the previously prepared extracts was developed. The irritation potential and viscosity were assessed for each of the formulations. The study demonstrated that the addition of these extracts to body wash gel formulations has a positive effect on their quality and may contribute to a decrease in skin irritation. In summary, S. chinensis aqueous extracts can be seen as an innovative ingredient useful in the cosmetic and pharmaceutical industry.     

Chemical composition and antioxidant activity of Borago officinalis L. leaf extract growing in Algeria

The aqueous and hydroalcoholic extracts of borage (Borago officinalis) leaves from Annaba region (Algeria) were preliminary analyzed for their phenolic profile (total phenolics, total flavonoids, total flavonols, total tannins and total anthocyanins). These extracts were evaluated for their antioxidant properties by different methods such as DPPH radical scavenging, test NBT and total antioxidant activity. The two extracts have exhibited a high antiradical capacity. Indeed, the ethanolic extract showed the lower IC50 values and the highest amount of phenolics (94.09 ± 1.72 mg gallic acid/g dry extract). Using LC-MS/MS analysis, it was possible to identify phenolic acids, flavonoids, sterol and for the first time oleuropein was identified in the aqueous extract of the plant. The obtained results have demonstrated that phenolic compounds are the major contributor to the antioxidant activity of plants.     

In Vitro Antioxidant and Anticancer Properties of Various E. senegalensis Extracts

Although Erythrina senegalensis is a plant widely used in traditional medicine in sub-Saharan Africa, its biological properties have been poorly investigated to date. We first characterized by conventional reactions the composition of several stem bark extracts and evaluated in acellular and cellular assays their pro- or antioxidant properties supported by their high phenolic and flavonoid content, particularly with the methanolic extract. The pro- or antioxidant effects observed did not correlate with their IC₅₀ concentrations against five cancer cell lines determined by MTT assay. Indeed, the CH₂Cl₂ extract and its ethyl acetate (EtOAc) subfraction appeared more potent although they harbored lower pro- or antioxidant effects. Nevertheless, at equipotent concentration, both extracts induced ER- and mitochondria-derived vacuoles observed by fluorescent microscopy that further led to non-apoptotic cell death. LC coupled to high resolution MS investigations have been performed to identify chemical compounds of the extracts. These investigations highlighted the presence of compounds formerly isolated from E. senegalensis including senegalensein that could be retrieved only in the EtOAc subfraction but also thirteen other compounds, such as 16:3-Glc-stigmasterol and hexadecanoic acid, whose anticancer properties have been previously reported. Nineteen other compounds remain to be identified. In conclusion, E. senegalensis appeared rich in compounds with antioxidant and anticancer properties, supporting its use in traditional practice and its status as a species of interest for further investigations in anticancer drug research.     

Phenolic Building Blocks for the Assembly of Functional Materials

Phenolic materials have long been known for their use in inks, wood coatings, and leather tanning. However, there has recently been a renewed interest in engineering advanced materials from phenolic building blocks. The intrinsic properties of phenolic compounds, such as metal chelation, hydrogen bonding, pH responsiveness, redox potentials, radical scavenging, polymerization, and light absorbance, have made them a distinct class of structural motifs for the synthesis of functional materials. Materials prepared from phenolic compounds often retain many of these useful properties with synergistic effects in applications ranging from catalysis to biomedicine. This Review provides an overview of the diverse functional materials that can be prepared from natural and synthetic phenolic building blocks, as well as their applications.     

Phenolic compounds from Allium schoenoprasum, Tragopogon pratensis and Rumex acetosa and their antiproliferative effects

Experimental studies have shown that phenolic compounds have antiproliferative and tumour arresting effects. The aim of this original study was to investigate the content of phenolic compounds (PhC) in flowers of Allium schoenoprasum (chive), Tragopogon pratensis (meadow salsify) and Rumex acetosa (common sorrel) and their effect on proliferation of HaCaT cells. Antiproliferative effects were evaluated in vitro using the following concentrations of phenolic compounds in cultivation medium: 100, 75, 50 and 25 μg/mL. Phenolic composition was also determined by HPLC. The results indicate that even low concentrations of these flowers' phenolic compounds inhibited cell proliferation significantly and the possible use of the studied herb's flowers as sources of active phenolic compounds for human nutrition.     

Bioactive and Nutritional Potential of Medicinal and Aromatic Plant (MAP) Seasoning Mixtures

Medicinal and aromatic plants (MAPs), worldwide appreciated and used as condiments, dyes, and preservatives, possess several biological properties that justify their continuous application in the food industry. In the present study, the nutritional and chemical profiles, as well as the bioactive properties of four combinations of condiments, sold for seasoning poultry, meat, fish, and salads, were evaluated. Twenty-five phenolic compounds (HPLC-DAD-ESI/MS) were identified, with apigenin-O-malonyl-pentoside-hexoside as the major compound detected in all extracts. Oxalic and citric acids were identified in all mixtures (UFLC-PDA), as well as all the four tocopherol isoforms (HPLC-fluorescence). Regarding bioactivities, the mixtures for meat and salads (TBARS) and meat and poultry (OxHLIA) stood out for their antioxidant potential, whereas for the anti-inflammatory and antitumor properties, the mixtures revealing the greatest results were those for poultry and salad, respectively. In terms of antimicrobial activity, all the mixtures revealed the capacity to inhibit the growth of some bacterial strains. In brief, condiment mixtures showed to be a good source of bioactive compounds, as they confer health benefits, validating the importance of their inclusion in the human diet as a good dietary practice.     

Natural Polyphenols for the Preservation of Meat and Dairy Products

Food spoilage makes foods undesirable and unacceptable for human use. The preservation of food is essential for human survival, and different techniques were initially used to limit the growth of spoiling microbes, e.g., drying, heating, salting, or fermentation. Water activity, temperature, redox potential, preservatives, and competitive microorganisms are the most important approaches used in the preservation of food products. Preservative agents are generally classified into antimicrobial, antioxidant, and anti-browning agents. On the other hand, artificial preservatives (sorbate, sulfite, or nitrite) may cause serious health hazards such as hypersensitivity, asthma, neurological damage, hyperactivity, and cancer. Thus, consumers prefer natural food preservatives to synthetic ones, as they are considered safer. Polyphenols have potential uses as biopreservatives in the food industry, because their antimicrobial and antioxidant activities can increase the storage life of food products. The antioxidant capacity of polyphenols is mainly due to the inhibition of free radical formation. Moreover, the antimicrobial activity of plants and herbs is mainly attributed to the presence of phenolic compounds. Thus, incorporation of botanical extracts rich in polyphenols in perishable foods can be considered since no pure polyphenolic compounds are authorized as food preservatives. However, individual polyphenols can be screened in this regard. In conclusion, this review highlights the use of phenolic compounds or botanical extracts rich in polyphenols as preservative agents with special reference to meat and dairy products.     

Bioactive compounds, RP-HPLC analysis of phenolics, and antioxidant activity of some Portuguese shrub species extracts

In the ecosystem of Serra Da Estrela, some plant species have the potential to be used as raw material for extraction of bioactive products. The goal of this work was to determine the phenolic, flavonoid, tannin and alkaloid contents of the methanolic extracts of some shrubs (Echinospartum ibericum, Pterospartum tridentatum, Juniperus communis, Ruscus aculeatus, Rubus ulmifolius, Hakea sericea, Cytisus multiflorus, Crataegus monogyna, Erica arborea and Ipomoea acuminata), and then to correlate the phenolic compounds and flavonoids with the antioxidant activity of each extract. The Folin-Ciocalteu's method was used for the determination of total phenols, and tannins were then precipitated with polyvinylpolypyrrolidone (PVPP); a colorimetric method with aluminum chloride was used for the determination of flavonoids, and a Dragendorff's reagent method was used for total alkaloid estimation. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and beta-carotene bleaching tests were used to assess the antioxidant activity of extracts. The identification of phenolic compounds present in extracts was performed using RP-HPLC. A positive linear correlation between antioxidant activity index and total phenolic content of methanolic extracts was observed. The RP-HPLC procedure showed that the most common compounds were ferulic and ellagic acids and quercetin. Most of the studied shrubs have significant antioxidant properties that are probably due to the existence of phenolic compounds in the extracts. It is noteworthy to emphasize that for Echinospartum ibericum, Hakea sericea and Ipomoea acuminata, to the best of our knowledge, no phytochemical studies have been undertaken nor their use in traditional medicine been described.     

Rhamnus pallasii subsp. sintenisii fruit,leaf, bark and root: Phytochemical profiles and biological activities

The genus Rhamnus has received a lot of interest as a source of phenolic chemicals. There have been no reports on the phytochemicals and biological activities of R. pallasii subsp. sintenisii various morphological components (fruit, leaf, bark, and root) in Iran to yet. Two crude ether petroleum (EP) and hydro-methanolic (HM) extracts were obtained from the separate parts. The antioxidant and antibacterial capabilities of the extracts, as well as their phytochemical screening (total phenolic, flavonoid, phenolic acid, and anthocyanin concentrations), were measured. Furthermore, the phytochemical profiles of EP and HM extracts were determined using GC–MS and LC-ESI–MS, respectively. LC-ESI-MS detected 59 chemicals in HM extracts, including flavonoids (62.71 %), phenolic acids (10.16 %), and anthraquinones (16.94 %). Furthermore, the predominant group components in EP extracts examined by GC–MS were fatty acids (58.82%), phenolic compounds (49.28%), and hydrocarbons (35.15 to 59.45 %). In terms of biological testing (DPPH radical scavenging and anti-bacterial activity), all examined extracts, particularly the fruit, had the highest activities in both assays (IC₅₀: 7.52 to 22.39 µg/ml and MIC: 0.39 to 3.12 mg/ml), owing to their high phenolic content. As a result, individual morphological elements of the species might be thought of as natural antioxidant and antibacterial agents.