Overview of Caffeine Effects on Human Health and Emerging Delivery Strategies.

Caffeine is a naturally occurring alkaloid found in various plants. It acts as a stimulant, antioxidant, anti-inflammatory, and even an aid in pain management, and is found in several over-the-counter medications. This naturally derived bioactive compound is the best-known ingredient in coffee and other beverages, such as tea, soft drinks, and energy drinks, and is widely consumed worldwide. Therefore, it is extremely important to research the effects of this substance on the human body. With this in mind, caffeine and its derivatives have been extensively studied to evaluate its ability to prevent diseases and exert anti-aging and neuroprotective effects. This review is intended to provide an overview of caffeine's effects on cancer and cardiovascular, immunological, inflammatory, and neurological diseases, among others. The heavily researched area of caffeine in sports will also be discussed. Finally, recent advances in the development of novel nanocarrier-based formulations, to enhance the bioavailability of caffeine and its beneficial effects will be discussed.

Blackberries and Mulberries: Berries with Significant Health-Promoting Properties.

Blackberries and mulberries are small and perishable fruits that provide significant health benefits when consumed. In reality, both are rich in phytochemicals, such as phenolics and volatile compounds, and micronutrients, such as vitamins. All the compounds are well-known thanks to their medicinal and pharmacological properties, namely antioxidant, anti-inflammatory, anti-cancer, antiviral, and cardiovascular properties. Nevertheless, variables such as genotype, production conditions, fruit ripening stage, harvesting time, post-harvest storage, and climate conditions influence their nutritional composition and economic value. Given these facts, the current review focuses on the nutritional and chemical composition, as well as the health benefits, of two blackberry species (Rubus fruticosus L., and Rubus ulmifolius Schott) and one mulberry species (Morus nigra L.).

Anti-Inflammatory and Antimicrobial Activities of Portuguese Prunus avium L. (Sweet Cherry) By-Products Extracts.

The bioactivity of natural by-products in food and pharmaceutical applications is the subject of numerous studies. Cherry production and processing generates large amounts of biowaste, most of which is not used. The recovery of these by-products is essential for promoting the circular economy and to improving sustainability in the food industry. In this work, we explored the anti-inflammatory and antimicrobial potential of two different extracts from stems, leaves, and flowers of Portuguese cherries. The anti-inflammatory potential was studied on lipopolysaccharide (LPS)-stimulated mouse macrophages (RAW 264.7) by evaluating the effect of by-products on cellular viability and nitric oxide (NO) production. Disc diffusion and minimum inhibitory concentration (MIC) were used to determine antimicrobial activity. The cherry by-products had no cytotoxic effect on RAW 264.7 cells, and were able to inhibit nitrite production in a dose-dependent manner. Moreover, all aqueous infusions showed good antioxidant activity against NO radicals. Moreover, leaf extracts showed the best activity against most of the strains studied. The results revealed, for the first time, interesting anti-inflammatory and antimicrobial properties of cherry by-products. This could potentially be of interest for their therapeutic use in the treatment of inflammation-related diseases or in controlling the growth of microorganisms.

Effects of Functional Phenolics Dietary Supplementation on Athletes' Performance and Recovery: A Review.

In recent years, many efforts have been made to identify micronutrients or nutritional strategies capable of preventing, or at least, attenuating, exercise-induced muscle damage and oxidative stress, and improving athlete performance. The reason is that most exercises induce various changes in mitochondria and cellular cytosol that lead to the generation of reactive species and free radicals whose accumulation can be harmful to human health. Among them, supplementation with phenolic compounds seems to be a promising approach since their chemical structure, composed of catechol, pyrogallol, and methoxy groups, gives them remarkable health-promoting properties, such as the ability to suppress inflammatory processes, counteract oxidative damage, boost the immune system, and thus, reduce muscle soreness and accelerate recovery. Phenolic compounds have also already been shown to be effective in improving temporal performance and reducing psychological stress and fatigue. Therefore, the aim of this review is to summarize and discuss the current knowledge on the effects of dietary phenolics on physical performance and recovery in athletes and sports practitioners. Overall, the reports show that phenolics exert important benefits on exercise-induced muscle damage as well as play a biological/physiological role in improving physical performance.

Zimbro (Juniperus communis L.) as a Promising Source of Bioactive Compounds and Biomedical Activities: A Review on Recent Trends.

Plant-derived products and their extracted compounds have been used in folk medicine since early times. Zimbro or common juniper (Juniperus communis) is traditionally used to treat renal suppression, acute and chronic cystitis, bladder catarrh, albuminuria, leucorrhea, and amenorrhea. These uses are mainly attributed to its bioactive composition, which is very rich in phenolics, terpenoids, organic acids, alkaloids, and volatile compounds. In the last few years, several studies have analyzed the huge potential of this evergreen shrub, describing a wide range of activities with relevance in different biomedical discipline areas, namely antimicrobial potential against human pathogens and foodborne microorganisms, notorious antioxidant and anti-inflammatory activities, antidiabetic, antihypercholesterolemic and antihyperlipidemic effects, and neuroprotective action, as well as antiproliferative ability against cancer cells and the ability to activate inductive hepato-, renal- and gastroprotective mechanisms. Owing to these promising activities, extracts and bioactive compounds of juniper could be useful for the development of new pharmacological applications in the treatment of several acute and chronic human diseases.

Anti-Inflammatory and Antiproliferative Properties of Sweet Cherry Phenolic-Rich Extracts.

Cherries have largely been investigated due to their high content in phenolics in order to fully explore their health-promoting properties. Therefore, this work aimed to assess, for the first time, the anti-inflammatory potential of phenolic-targeted fractions of the Saco cherry, using RAW 264.7 macrophages stimulated with lipopolysaccharide. Additionally, the cytotoxic effects on gastric adenocarcinoma (AGS), neuroblastoma (SH-SY5Y) and normal human dermal fibroblast (NHDF) cells were evaluated, as well as the ability to protect these cellular models against induced oxidative stress. The obtained data revealed that cherry fractions can interfere with cellular nitric oxide (NO) levels by capturing NO radicals and decreasing inducible nitric oxide synthase and cyclooxygenase-2 expression. Furthermore, it was observed that all cherry fractions exhibited dose-dependent cytotoxicity against AGS cells, presenting cytotoxic selectivity for these cancer cells when compared to SH-SY5Y and NHDF cells. Regarding their capacity to protect cancer cells against oxidative injury, in most assays, the total cherry extract was the most effective. Overall, this study reinforces the idea that sweet cherries can be incorporated into new pharmaceutical products, smart foods and nutraceuticals.

Sweet cherry phenolics revealed to be promising agents in inhibiting P-glycoprotein activity and increasing cellular viability under oxidative stress conditions: in vitro and in silico study.

This study aimed to explore the total phenolic and anthocyanin content (TPC and TAC, respectively), and the biological potential of Portuguese sweet cherry cultivars. The TPC and TAC values ranged between 72.9 and 493.6 gallic acid equivalents per 100 g fresh weight (fw), and from 1.0 to 179.1 cyanidin 3-O-rutinoside equivalents per 100 g fw, respectively. Cristalina total extract was the most effective in capturing DPPH reactive species, whereas the colored fraction and the total extract of Saco cultivar were the most efficient in scavenging ferric and peroxide species. Celeste total extract was the most effective in inhibiting α-glucosidase enzyme. Phenolic-rich extracts and standard phenolics also revealed ability to interfere with the P-gp activity on MDCK-II and MDCK-MDR1 cells and to increase cellular viability under conditions of oxidative stress. Computational studies were performed to evaluate the interaction between phenolics and the P-gp activity. This study revealed that cherry extracts and their phenolic compounds present notable biological properties, encouraging the development of cherry-based dietary and medicinal supplements. PRACTICAL APPLICATION: The interest in phenolic-rich sources has increased significantly in recent years, given their capacity to prevent the development of chronic disorders, such as cancer. Recent evidence suggests that phenolic compounds can act as P-glycoprotein (P-gp) inhibitors, an important drug efflux transporter, preventing multidrug resistance, and thus, enhancing the therapeutic efficacy of some drugs in certain target cells. Our results indicate that enriched-fractions from sweet cherries can effectively interfere with the P-gp activity on MDCK-II and MDCK-MDR1 cells and protect against oxidative damage.

Potential Activity of Abrantes Pollen Extract: Biochemical and Cellular Model Studies.

The aim of this study was to determine the grain composition and (poly)phenolic profile of pollen from Abrantes (Portugal), as well as its antioxidative and antidiabetic properties, and abilities to protect human erythrocytes against induced hemoglobin oxidation, lipid peroxidation, and hemolysis. The phytochemical profile of the Abrantes' bee pollen revealed twenty phenolic compounds, identified by high-performance liquid chromatography with electrospray ionization mass spectrometry coupled with photodiode array detection. Among them, quercetin derivatives were the most abundant. Concerning the biological potential, the pollen extract showed notable capacity for 2,2-diphenyl-1-picrylhydrazyl, nitric oxide, and superoxide radicals, as well as for inhibition of α-glucosidase action, and protection of human erythrocytes against oxidative damage. Non-cytotoxic effects regarding the NHDF normal cell line, human adenocarcinoma Caco-2, and human liver HepG2 cells were observed. The results obtained contributed to further research on modes of action related to oxidative damage and metabolic health problems, to generate deeper knowledge of potential health-promoting effects to develop novel pharmaceutical drugs, nutraceuticals, and dietary supplements.

Valorisation of Prunus avium L. By-Products: Phenolic Composition and Effect on Caco-2 Cells Viability.

Prunus avium L. by-products, such as stems, leaves, and flowers, are used in folk medicine to prevent and treat some diseases. However, their phenolic composition and in vitro bioactivities against tumor cells are poorly known. In this work, we compared the phenolic profile and the biological potential of aqueous infusions and hydroethanolic extracts of P. avium leaves, stems, and flowers from Saco cultivar, collected from the Fundão region (Portugal). Among the fifty-two phenolic compounds tentatively identified by HPLC-DAD-ESI/MSn, the hydroxycinnamic acids were the most abundant. Both extracts of stems revealed a higher activity against DPPH•. Meanwhile, hydroethanolic extracts from stems and flowers and aqueous infusions of flowers were the most effective in inhibiting the growth of the human epithelial colorectal adenocarcinoma (Caco-2) cells at concentrations above 200 µg/mL. More detailed knowledge about the phenolic composition and health-promoting properties of Portuguese P. avium by-products allows for increasing the biological and commercial value of these bio-wastes, which may have a positive impact on food and pharmaceutical industries, as on the valorization of the local economy.

Development of bioactive films based on chitosan and Cynara cardunculus leaves extracts for wound dressings.

The development of natural based, effective and protective wound dressings associated to local treatment applied on chronic wounds, represents a major challenge nowadays. In this work chitosan-based films were prepared with different concentrations of ethanolic ultrasound assisted extracts from Cynara cardunculus leaves (EtPUAE). The physico-chemical film properties revealed that extract incorporation influences the volumetric swelling capacity and mechanical properties of the films, leading to materials with a lower fluid absorption capacity and more fragile. However, no impact was detected on the thermal properties of the films, as well as on their dense structure characterized by Scanning Electronic Microscopy (SEM) analysis. Biological screening of chitosan-based films show that chitosan with a 1% (w/w) and a 5% (w/w) EtPUAE loading did not induce cytotoxicity on normal human skin fibroblasts (Bj5-ta cell line), mainly attributed to cynaropicrin (extract key active compound) present in the film below its IC50 value. Nevertheless, chitosan-based films with 5% (w/w) EtPUAE presented an interesting anti-inflammatory activity. Bj5-ta cells stimulated with liposaccharides (LPS), presented a reduction of 86% on IL-6 cytokine levels, after exposure to chitosan with 5% EtPUAE film extract. The results obtained in this study open up the possibility of successfully using chitosan films doped with EtPUAE for development of chronic wound dressings, with the advantage of using naturally-sourced materials with anti-inflammatory activity.

Authentication of honeys from Caramulo region (Portugal): Pollen spectrum, physicochemical characteristics, mineral content, and phenolic profile.

This study aimed to analyze the botanical origin, quality parameters, phenolic compounds, and minerals of 20 honey samples from Caramulo region (Portugal). Six samples were monofloral from Eucalyptus sp., being this one the predominant pollen in the analyzed samples, followed by Castanea sativa. The average values obtained for the physicochemical parameters were as follows: 4.7 pH; 16.8% moisture; 81.4 Brix; 0.3% ash; 512.8 µS/cm electrical conductivity; 22.6 meq/kg free acidity; 12.4 meq/kg lactonic acidity; 35.1 meq/kg total acidity; 2.1 mg/kg hydroxymethylfurfural; and 16.3 °Gothe for diastase activities. A total of 18 phenolics were determined by high-performance liquid chromatography-diode array detector. Hydroxycinnamic acid derivatives and protocatechuic acid were the major ones. Nine minerals were detected by atomic absorption spectrometry; potassium and phosphorus were the predominant mineral elements. This is the first study about honeys from Caramulo region, which revealed to have a good quality and be a rich source of essential minerals and phenolics. PRACTICAL APPLICATION: The interest in the analysis of honey has increased significantly in recent years, concerning its characterization, safety implications, and health impact. Given these facts, the authentication of honeys, based on the geographical and botanical origins, has been assuming great importance, being mainly associated with high-quality honeys. Therefore, we decided to analyze physicochemical parameters, phenolic composition, and mineral content of 20 Caramulo honey samples. Our results indicate that Caramulo honeys possess high-quality levels, good freshness, maturity, and proper processing, and are also rich in several bioactive substances with health-promoting properties, including phenolic compounds, potassium, and phosphorus.

Exploring the phenolic profile, antioxidant, antidiabetic and anti-hemolytic potential of Prunus avium vegetal parts.

The aim of the present work was to evaluate the phenolic profile of leaves, stems and flowers of P. avium and their biological potential. For this purpose, two extracts of each matrix (hydroethanolic and infusion) were prepared. A total of twenty-six phenolics were identified by LC-DAD, including 1 hydroxybenzoic acid, 9 hydroxycinnamic acids, 7 flavonols, 3 isoflavones, 3 flavanones and 3 flavan-3-ols, being the hydroethanolic leaves extract the richest one. 5-O-caffeoylquinic acid, hydroxycinnamic derivative 1 and sakuranetin derivative were the major compounds found in leaves, flowers and stems, respectively. The hydroethanolic extracts of stems and leaves proved to be the most active against DPPH• and O2•- (IC50 = 22.37 ±â€¯0.29 µg/mL and IC50 = 9.11 ±â€¯0.16 µg/mL, respectively). On the other hand, the infusion extract of stems showed the highest antioxidant activity against •NO (IC50 = 99.99 ±â€¯1.89 µg/mL). The antidiabetic potential was tested using the α-glucosidase enzyme, being the infusion extract of stems the most active, with an IC50 = 3.18 ±â€¯0.23 µg/mL. Finally, the protective effect of the extracts towards human erythrocytes against oxidative damage was also evaluated. The hydroethanolic extract of stems was the most active against lipid peroxidation and hemolysis with an IC50 = 26.20 ±â€¯0.38 µg/mL and IC50 = 1.58 ±â€¯0.18 µg/mL, respectively. On the other hand, the hydroethanolic extract of flowers showed the greater protective effect against hemoglobin oxidation (IC50 = 12.85 ±â€¯0.61 µg/mL). Considering the results obtained in this work, we can consider that leaves, stems and flowers of P. avium are a promising source of bioactive compounds and present health-promoting properties.

Antioxidant Status, Antidiabetic Properties and Effects on Caco-2 Cells of Colored and Non-Colored Enriched Extracts of Sweet Cherry Fruits.

This study aimed to compare three different extracts of Saco sweet cherry, namely the non-colored fraction, colored fraction, and total extract concerning phenolic composition, antioxidant and antidiabetic potential, and erythrocytes' protection and effects on Caco-2 cells. Twenty-two phenolic compounds were identified using high-performance liquid chromatography with diode-array detection. Hydroxycinnamic acids were the most predominant in both the non-colored fraction and total extract, while cyanidin-3-O-rutinoside was the main anthocyanin found in the colored fraction. The total extract was the most effective against 1,1-diphenyl-2-picrylhydrazyl, nitric oxide, and superoxide radicals, and in the inhibition of α-glucosidase enzyme. The colored fraction revealed the best activity against hemoglobin oxidation and hemolysis. Regarding to Caco-2 cells, the colored extract exhibited the highest cytotoxic effects, while the total extract was the most efficient in protecting these cells against oxidative damage induced by tert-butyl hydroperoxide.

Sweet cherries from Fundão possess antidiabetic potential and protect human erythrocytes against oxidative damage.

Cherries are one of the most appreciated summer fruits due to their attractive colour, sweet taste, high water content, low level of calories and composition in bioactive compounds which, in turn, are important to prevent some pathologies like diabetes, cardiovascular diseases and cancer. In this work we evaluated the phenolic profile and biological potential of 5 varieties of sweet cherries from Fundão region (Portugal) (Saco, Sweetheart, Satin, Maring and Hedelfinger). A total of 23 phenolic compounds were identified by LC-DAD and distributed by the several classes: 6 anthocyanins, 1 hydroxybenzoic acid, 8 hydroxycinnamic acids, 3 flavan-3-ols and 5 flavonols. Maring revealed higher contents in anthocyanins, while Hedelfinger was the richest in non-coloured phenolics. The antioxidant capacity was evaluated against DPPH and nitric oxide radicals. Hedelfinger was the most active against DPPH• (IC50=12.1µg/mL) and Maring against nitric oxide (IC50=140.9µg/mL). Afterwards, antidiabetic capacity was evaluated through the inhibition of α-glucosidase activity, pointing Hedelfinger as the most active (IC50=10.3µg/mL). The capacity of Saco extracts to inhibit the hemoglobin oxidation and the hemolysis of human erythrocytes was also evaluated. Both assays revealed a concentration-dependent inhibitory effect (IC50=38.6µg/mL and IC50=73.0µg/mL, respectively). The results obtained in this study allow us to conclude that sweet cherries possess a great biological potential, and further investigation should be done to promote commercialization and encourage its use in food supplements and in new pharmaceutical and nutraceutical applications.