Impact of Melatonin Supplementation on Sports Performance and Circulating Biomarkers in Highly Trained Athletes: A Systematic Review of Randomized Controlled Trials.

Melatonin (N-acetyl-5 methoxytryptamine) is an indolic neurohormone that modulates a variety of physiological functions due to its antioxidant, anti-inflammatory, and immunoregulatory properties. Therefore, the purpose of this study was to critically review the effects of melatonin supplementation in sports performance and circulating biomarkers related to the health status of highly trained athletes. Data were obtained by performing searches in the following three bibliography databases: Web of Science, PubMed, and Scopus. The terms used were "Highly Trained Athletes", "Melatonin", and "Sports Performance", "Health Biomarkers" using "Humans" as a filter. The search update was carried out in February 2024 from original articles published with a controlled trial design. The PRISMA rules, the modified McMaster critical review form for quantitative studies, the PEDro scale, and the Cochrane risk of bias were applied. According to the inclusion and exclusion criteria, 21 articles were selected out of 294 references. The dose of melatonin supplemented in the trials ranged between 5 mg to 100 mg administered before or after exercise. The outcomes showed improvements in antioxidant status and inflammatory response and reversed liver damage and muscle damage. Moderate effects on modulating glycemia, total cholesterol, triglycerides, and creatinine were reported. Promising data were found regarding the potential benefits of melatonin in hematological biomarkers, hormonal responses, and sports performance. Therefore, the true efficiency of melatonin to directly improve sports performance remains to be assessed. Nevertheless, an indirect effect of melatonin supplementation in sports performance could be evaluated through improvements in health biomarkers.

Analysis of Lemon Verbena Polyphenol Metabolome and Its Correlation with Oxidative Stress under Glucotoxic Conditions in Adipocyte.

Lemon verbena has been shown to ameliorate obesity-related oxidative stress, but the intracellular final effectors underlying its antioxidant activity are still unknown. The purpose of this study was to correlate the antioxidant capacity of plasma metabolites of lemon verbena (verbascoside, isoverbascoside, hydroxytyrosol, caffeic acid, ferulic acid, homoprotocatechuic acid, and luteolin-7-diglucuronide) with their uptake and intracellular metabolism in hypertrophic adipocytes under glucotoxic conditions. To this end, intracellular ROS levels were measured, and the intracellular metabolites were identified and quantified by high-performance liquid chromatography with a diode array detector coupled to mass spectrometry (HPLC-DAD-MS). The results showed that the plasma metabolites of lemon verbena are absorbed by adipocytes and metabolized through phase II reactions and that the intracellular appearance of these metabolites correlates with the decrease in the level of glucotoxicity-induced oxidative stress. It is postulated that the biotransformation and accumulation of these metabolites in adipocytes contribute to the long-term antioxidant activity of the extract.

Acute Antioxidant Response to Two Types of Exercises: 2000 M Run vs. Burpee Test.

Physical activity results in oxidative stress, as evidenced by the increased production of reactive oxygen, nitrogen species, and inflammatory mediators. The management of these components is instrumental for antioxidant adaptation to exercise and post-exercise recovery. Therefore, the present report aims to study the antioxidant response to two types of exercise (a 2000 m run and a burpee test) in healthy volunteers after a long period of inactivity (1-2 months). Antioxidant enzyme activities and oxidative stress markers (protein carbonyls and malondialdehyde content) were measured in neutrophils, peripheral blood mononuclear cells, and plasma. These parameters were determined under basal conditions and immediately post-exercise. Compared to those in basal state, neutrophil superoxide dismutase (28.3 vs. 22.9 pkat/109 cells), glutathione peroxidase (147.5 vs. 120.1 nkat/109 cells), and catalase (106.3 vs. 57.9 k/109 cells) were activated significantly (p < 0.05) after the burpee test. Peripheral blood mononuclear cells exhibited only significant (p < 0.05) catalase activation (113.6 vs. 89.4 k/109 cells) after the burpee test. Other enzymes, such as glutathione reductase and myeloperoxidase, tended to increase post-exercise, although the differences from baseline were not significant. Finally, compared to basal conditions, the protein carbonyl (24.5 vs. 14.5 mmol/L) and malondialdehyde (39.6 vs. 18.3 mmol/L) contents increased significantly (p < 0.05) in neutrophils and in plasma (115.1 vs. 97.8 and 130.2 vs. 123.4 µmol/L, respectively) after the burpee test. In conclusion, high-intensity exercise seems to induce immediate oxidative stress in inactive individuals, and the acute antioxidant response was slightly greater after the burpee test than after the 2000 m run. Glutathione-dependent antioxidant systems are activated immediately as protective mechanisms.

Evaluation of Bioactive Effects of Five Plant Extracts with Different Phenolic Compositions against Different Therapeutic Targets.

Plant extracts rich in phenolic compounds have been reported to exert different bioactive properties. Despite the fact that there are plant extracts with completely different phenolic compositions, many of them have been reported to have similar beneficial properties. Thus, the structure-bioactivity relationship mechanisms are not yet known in detail for specific classes of phenolic compounds. In this context, this work aims to demonstrate the relationship of extracts with different phenolic compositions versus different bioactive targets. For this purpose, five plant matrices (Theobroma cacao, Hibiscus sabdariffa, Silybum marianum, Lippia citriodora, and Olea europaea) were selected to cover different phenolic compositions, which were confirmed by the phytochemical characterization analysis performed by HPLC-ESI-qTOF-MS. The bioactive targets evaluated were the antioxidant potential, the free radical scavenging potential, and the inhibitory capacity of different enzymes involved in inflammatory processes, skin aging, and neuroprotection. The results showed that despite the different phenolic compositions of the five matrices, they all showed a bioactive positive effect in most of the evaluated assays. In particular, matrices with very different phenolic contents, such as T. cacao and S. marianum, exerted a similar inhibitory power in enzymes involved in inflammatory processes and skin aging. It should also be noted that H. sabdariffa and T. cacao extracts had a low phenolic content but nevertheless stood out for their bioactive antioxidant and anti-radical capacity. Hence, this research highlights the shared bioactive properties among phenolic compounds found in diverse matrices. The abundance of different phenolic compound families highlights their elevated bioactivity against diverse biological targets.

Hallmarks and Biomarkers of Skin Senescence: An Updated Review of Skin Senotherapeutics.

Aging is a complex process characterized by an ongoing decline in physiological functions, leading to degenerative diseases and an increased probability of death. Cellular senescence has been typically considered as an anti-proliferative process; however, the chronic accumulation of senescent cells contributes to tissue dysfunction and aging. In this review, we discuss some of the most important hallmarks and biomarkers of cellular senescence with a special focus on skin biomarkers, reactive oxygen species (ROS), and senotherapeutic strategies to eliminate or prevent senescence. Although most of them are not exclusive to senescence, the expression of the senescence-associated beta-galactosidase (SA-ß-gal) enzyme seems to be the most reliable biomarker for distinguishing senescent cells from those arrested in the cell cycle. The presence of a stable DNA damage response (DDR) and the accumulation of senescence-associated secretory phenotype (SASP) mediators and ROS are the most representative hallmarks for senescence. Senotherapeutics based on natural compounds such as quercetin, naringenin, and apigenin have shown promising results regarding SASP reduction. These compounds seem to prevent the accumulation of senescent cells, most likely through the inhibition of pro-survival signaling pathways. Although studies are still required to verify their short- and long-term effects, these therapies may be an effective strategy for skin aging.

The Vascular Niche for Adult Cardiac Progenitor Cells.

Research on cardiac progenitor cell populations has generated expectations about their potential for cardiac regeneration capacity after acute myocardial infarction and during physiological aging; however, the endogenous capacity of the adult mammalian heart is limited. The modest efficacy of exogenous cell-based treatments can guide the development of new approaches that, alone or in combination, can be applied to boost clinical efficacy. The identification and manipulation of the adult stem cell environment, termed niche, will be critical for providing new evidence on adult stem cell populations and improving stem-cell-based therapies. Here, we review and discuss the state of our understanding of the interaction of adult cardiac progenitor cells with other cardiac cell populations, with a focus on the description of the B-CPC progenitor population (Bmi1+ cardiac progenitor cell), which is a strong candidate progenitor for all main cardiac cell lineages, both in the steady state and after cardiac damage. The set of all interactions should be able to define the vascular cardiac stem cell niche, which is associated with low oxidative stress domains in vasculature, and whose manipulation would offer new hope in the cardiac regeneration field.

Bioactive Antioxidant Compounds from Chestnut Peels through Semi-Industrial Subcritical Water Extraction.

Chestnut peels are a poorly characterized, underexploited by-product of the agri-food industry. This raw material is rich in bioactive compounds, primarily polyphenols and tannins, that can be extracted using different green technologies. Scaling up the process for industrial production is a fundamental step for the valorization of the extract. In this study, subcritical water extraction was investigated to maximize the extraction yield and polyphenol content. Lab-scale procedures have been scaled up to the semi-industrial level as well as the downstream processes, namely, concentration and spray drying. The extract antioxidant capacity was tested using in vitro and cellular assays as well as a preliminary evaluation of its antiadipogenic activity. The temperature, extraction time, and water/solid ratio were optimized, and the extract obtained under these conditions displayed a strong antioxidant capacity both in in vitro and cellular tests. Encouraging data on the adipocyte model showed the influence of chestnut extracts on adipocyte maturation and the consequent potential antiadipogenic activity. Chestnut peel extracts characterized by strong antioxidant power and potential antiadipogenic activity were efficiently obtained by removing organic solvents. These results prompted further studies on fraction enrichment by ultra- and nanofiltration. The semi-industrial eco-friendly extraction process and downstream benefits reported here may open the door to production and commercialization.

High global antioxidant protection and stimulation of the collagen synthesis of new anti-aging product containing an optimized active mix.

OBJECTIVE: To assess the in vitro efficacy on antioxidant potential, protection against global oxidative stress, and effect on collagen neosynthesis of minimalist formula (Peptide-C ampoules product) containing 10% natural vitamin C, rice and lupin bio-peptides, hyaluronic acid, and Vichy volcanic mineralizing water (active mix). METHODS: In-tube quantitative tests ("in-tube screening") assessed global antioxidant properties, anti-lipid peroxidation, anti-protein glycosylation, and metalloproteinase inhibition (anti-collagenase, anti-elastase, and anti-hyaluronidase activity) properties of the formula. Protection against oxidative stress was evaluated on human keratinocyte monolayer cultures, and collagen neosynthesis was quantified on fibroblast monolayer cultures treated with supernatants from product-treated reconstructed human epidermis. RESULTS: Product (5% concentration) showed high antioxidant ability (blocking 99.0% oxidation), protection against oxidative stress damage (51.8% lipid peroxidation and 37.8% protein glycosylation decreases), and inhibition of hyaluronidase (21.9%), elastase (47.1%), and collagenase (61.8%). The protective effect was validated on human keratinocyte monolayer cultures in the presence of active mix (0.025%). Oxidative stress (ROS) was reduced by 99.0%, while global oxidative stress (RMS) induced by pollution, UVA radiation, and a combination of both factors was reduced by 48.94%, 8.7%, and 96.28%, respectively. The product increased collagen neosynthesis (11.21%) by cellular dialogue in fibroblasts incubated with product/mix-treated-RHE supernatants. CONCLUSION: The combination of ingredients in the product showed high global antioxidant capacity, as well as a protective effect against oxidative stress induced by UVA, pollution, or both combined factors and an ability to stimulate collagen neosynthesis in in vitro studies, which support the clinical efficacy of this product.

Modulation of Oxidative Stress and Antioxidant Response by Different Polyphenol Supplements in Five-a-Side Football Players.

Oxidative stress is associated with playing soccer. The objective of the present report was to study the influence of different polyphenolic antioxidant-rich beverages in five-a-side/futsal players. The study was performed with a no supplemented control group (CG) and two supplemented groups with an almond-based beverage (AB) and the same beverage fortified with Lippia citriodora extract (AB + LE). At day 22, participants played a friendly futsal game. Blood extractions were performed at the beginning of intervention (day 1), before and after match (day 22) to determine oxidative stress markers and antioxidant enzyme activities in plasma, neutrophils and peripheral blood mononuclear cells (PBMCs). Malondialdehyde increased significantly in controls after the match in neutrophils, PBMCs and plasma compared to pre-match. Protein carbonyls also increased after the match in plasma in CG. In addition, malondialdehyde levels in neutrophils were significantly lower in the supplemented groups compared to controls. Post-match samples showed significant increases in neutrophil antioxidant activities in CG. Supplemented groups displayed variable results regarding neutrophil antioxidant activities, with superoxide dismutase activity significantly lower than in controls. Finally, post-match myeloperoxidase activity increased significantly in controls compared to pre-match and supplemented groups. In conclusion, polyphenolic antioxidant and anti-inflammatory supplements could be instrumental for optimal recovery after high intensity futsal games.

Antioxidant Supplementation Modulates Neutrophil Inflammatory Response to Exercise-Induced Stress.

The aim of the present report was to evaluate the inflammatory response to a 2000-m running test considering neutrophil myeloperoxidase as an inflammatory marker, and to verify if supplements rich in antioxidants could modulate Post-test antioxidant and anti-inflammatory responses. To this end, a 21-day homogenization period was carried out with three groups: a control group, a supplemented group taking an almond beverage enriched with vitamins C and E and a third group consuming the same beverage but enriched with Lippia citriodora extract. At the end of this period, participants performed a 2000-m run, and blood samples were obtained the day before and immediately after the running test. Plasma and neutrophils were isolated. As a result, plasma creatine kinase and myoglobin increased, indicating Post-test muscle damage. Plasma oxidative markers were increased in all groups, except in the group supplemented with the almond beverage. Neutrophil antioxidant enzymes were significantly increased only in the control group, suggesting an antioxidant effect of the supplements provided in the other groups. Myeloperoxidase activity was significantly increased after the test in the control group, while increased enzyme levels were detected in plasma of the supplement groups. Therefore, antioxidant consumption seems to favour myeloperoxidase release. The connection of this observation with post-exercise recovery will require further investigation.

Antioxidants and Skin Protection.

Natural products have a long history of use for skincare and the improvement of the appearance and function of aged and/or damaged skin [...].

Quercetin metabolites from Hibiscus sabdariffa contribute to alleviate glucolipotoxicity-induced metabolic stress in vitro.

Polyphenols from Hibiscus sabdariffa (HS) alleviate obesity-related metabolic complications but the metabolites responsible for such effects are unknown. We aimed to elucidate which of the potential plasma metabolites from a polyphenol-enriched HS (PEHS) extract contributed for the reversion of glucolipotoxicity-induced metabolic stress using 3T3-L1 adipocyte and INS 832/13 pancreatic ß-cell models under glucolipotoxic conditions. PEHS extract, quercetin (Q) and quercetin-3-O-glucuronide (Q3GA) showed stronger capacity to decrease glucolipotoxicity-induced ROS generation than ascorbic acid or chlorogenic acid. PEHS extract, Q and Q3GA decreased secretion of cytokines (leptin, TNF-α, IGF-1, IL-6, VEGF, IL-1α, IL-1ß and CCL2) and reduced CCL2 expression at transcriptional level. In addition, PEHS extract, Q and Q3GA reduced triglyceride accumulation, which occurred through fatty acid synthase (FASN) downregulation, AMPK activation and mitochondrial mass and biogenesis restoration via PPARα upregulation. Electron microscopy confirmed that PEHS extract and Q3GA decreased mitochondrial remodeling and mitophagy. Virtual screening leads us to postulate that Q and Q3GA might act as agonists of these protein targets at specific sites. These data suggest that Q and Q3GA may be the main responsible compounds for the capacity of PEHS extract to revert glucolipotoxicity-induced metabolic stress through AMPK-mediated decrease in fat storage and increase in fatty acid oxidation, though other compounds of the extract may contribute to this capacity.

Sweet Cherry Byproducts Processed by Green Extraction Techniques as a Source of Bioactive Compounds with Antiaging Properties.

In the cosmetic industry, there is a continuous demand for new and innovative ingredients for product development. In the context of continual renovation, both cosmetic companies and customers are particularly interested in compounds derived from natural sources due to their multiple benefits. In this study, novel and green-extractive techniques (pressurized solvent, supercritical CO2, and subcritical water extractions) were used to obtain three new extracts from sweet cherry stems, a byproduct generated by the food industry. The extracts were characterized by high-performance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS), and 57 compounds, mainly flavonoids but also organic and phenolic acids, fatty acids, and terpenes, were identified. After analytical characterization, a multistep screening approach, including antioxidant, enzymatic, and photoprotective cellular studies, was used to select the best extract according to its benefits of interest to the cosmetics industry. The extract obtained with supercritical CO2 presented the best characteristics, including a wide antioxidant capacity, especially against lipid peroxyl and OH free radicals, as well as relevant photoprotective action and antiaging properties, making it a potential new ingredient for consideration in the development of new cosmetics.

Rosemary Diterpenes and Flavanone Aglycones Provide Improved Genoprotection against UV-Induced DNA Damage in a Human Skin Cell Model.

Overexposure to solar ultraviolet (UV) radiation is the major cause of a variety of cutaneous disorders, including sunburn, photoaging, and skin cancers. UVB radiation (290-320 nm) causes multiple forms of DNA damage, p53 induction, protein and lipid oxidation, and the generation of harmful reactive oxygen species (ROS). In recent years, botanicals containing polyphenols with antioxidant and anti-inflammatory properties as skin photoprotective agents have emerged. This study evaluated the protective effects of two formulations against UVB-induced damage in a skin cell model. One of the formulations (F2) contained a combination of citrus and olive extracts and the other one (F1) also contained a rosemary extract. The antioxidant capacity of both formulations was estimated by different in vitro methods, and the cell viability, intracellular ROS generation, mitochondrial depolarization, and DNA damage were studied in UVB-irradiated human keratinocytes. Both formulations exerted photoprotective effects on skin cells and decreased mitochondrial depolarization and DNA damage. F1 which contained iridoids, rosemary diterpenes, glycosides and aglycones of citrus flavanones, and monohydroxylated flavones exhibited higher cellular photoprotective effects and mitochondrial membrane potential restoration, as well as an enhanced capacity to decrease DNA double strand breaks and the DNA damage response. In contrast, F2, which contained mostly iridoids, citrus flavanone aglycones, and mono- and dihydroxylated flavones, exhibited a higher capacity to decrease intracellular ROS generation and radical scavenging capacity related to metal ion chelation. Both formulations showed a similar capability to decrease the number of apoptotic cells upon UVB radiation. Based on our results and those of others, we postulate that the stronger capacity of F1 to protect against UVB-induced DNA damage in human keratinocytes is related to the presence of rosemary diterpenes and citrus flavanone aglycones. Nevertheless, the presence of the dihydroxylated flavones in F2 may contribute to inhibiting the generation of metal-related free radicals. To confirm the efficacy of these formulations as potential candidates for oral/topical photoprotection, human trials are required to circumvent the limitations of the cellular model.

Calorie Restriction Improves Physical Performance and Modulates the Antioxidant and Inflammatory Responses to Acute Exercise.

Our aim was to characterize the effects of calorie restriction on the anthropometric characteristics and physical performance of sportsmen and to evaluate the effects of calorie restriction and acute exercise on mitochondria energetics, oxidative stress, and inflammation. Twenty volunteer taekwondo practitioners undertook a calorie restriction of 30-40% on three alternate days a week for one month. Eleven volunteer sportsmen participated as controls. Both groups performed an energy efficiency test to evaluate physical performance, and samples were taken before and after exercise. The total weight of participants significantly decreased (5.9%) after calorie restriction, while the efficiency of work and the contributions of fat to obtain energy were enhanced by calorie restriction. No significant differences induced by acute exercise were observed in individual non-esterified fatty acid percentage or oxidative stress markers. Calorie restriction downregulated the basal gene expression of nitric oxide synthase, antioxidant enzymes, mitochondrial uncoupling proteins, and repairing stress proteins, but it enhanced the expression of sirtuins in peripheral blood mononuclear cells. In conclusion, one month of calorie restriction decreases body weight and increases physical performance, enhancing energy efficiency, moderating the antioxidant and inflammatory basal gene expression, and influencing its response to acute exercise.

The Potential Synergistic Modulation of AMPK by Lippia citriodora Compounds as a Target in Metabolic Disorders.

Lippia citriodora (LC) represents a complex plant-derived source of polyphenols and iridoids that has shown beneficial properties against obesity-related metabolic disorders. The complete extract and its major compound, verbascoside, have shown AMPK-activating capacity in cell and animal models. In this work, we aimed to elucidate the contribution of the different compounds present in the LC extract on the AMPK activation capacity of the whole extract. Semipreparative reversed-phase high-performance liquid chromatography coupled to electrospray ionization time-of-flight mass spectrometry (RP-HPLC-ESI-TOF-MS) was used to identify the major compounds with bioassay-guided fractionation in an adipocyte cell model for the measurement of AMPK activity. Twenty-two compounds were identified and purified almost to homogeneity in 16 fractions, and three compounds, namely verbascoside, luteolin-7-diglucuronide and loganic acid, showed the highest AMPK-activating capacity. The synergy study using the checkerboard and fractional inhibitory concentration index (FICI) methods exhibited synergistic behavior between loganic acid and luteolin-7-diglucuronide. Molecular docking experiments revealed that these three compounds might act as direct agonists of AMPK, binding to the AMP binding sites of the gamma subunit and/or the different sites of the interaction zones between the gamma and beta subunits. Although our findings conclude that the bioactivity of the extract is mainly due to verbascoside, the synergy found between loganic acid and luteolin-7-diglucuronide deserves further research aimed to develop optimized combinations of polyphenols as a new nutritional strategy against obesity-related metabolic disorders.

Marine Invertebrate Extracts Induce Colon Cancer Cell Death via ROS-Mediated DNA Oxidative Damage and Mitochondrial Impairment.

Marine compounds are a potential source of new anticancer drugs. In this study, the antiproliferative effects of 20 invertebrate marine extracts on three colon cancer cell models (HGUE-C-1, HT-29, and SW-480) were evaluated. Extracts from two nudibranchs (Phyllidia varicosa, NA and Dolabella auricularia, NB), a holothurian (Pseudocol ochirus violaceus, PS), and a soft coral (Carotalcyon sp., CR) were selected due to their potent cytotoxic capacities. The four marine extracts exhibited strong antiproliferative effects and induced cell cycle arrest at the G2/M transition, which evolved into early apoptosis in the case of the CR, NA, and NB extracts and necrotic cell death in the case of the PS extract. All the extracts induced, to some extent, intracellular ROS accumulation, mitochondrial depolarization, caspase activation, and DNA damage. The compositions of the four extracts were fully characterized via HPLC-ESI-TOF-MS analysis, which identified up to 98 compounds. We propose that, among the most abundant compounds identified in each extract, diterpenes, steroids, and sesqui- and seterterpenes (CR); cembranolides (PS); diterpenes, polyketides, and indole terpenes (NA); and porphyrin, drimenyl cyclohexanone, and polar steroids (NB) might be candidates for the observed activity. We postulate that reactive oxygen species (ROS) accumulation is responsible for the subsequent DNA damage, mitochondrial depolarization, and cell cycle arrest, ultimately inducing cell death by either apoptosis or necrosis.

Relationships Between Chemical Structure and Antioxidant Activity of Isolated Phytocompounds from Lemon Verbena.

Over the last few years, people have been concerned about the narrow relationship between nutrition and health leading to an increasing demand of nutraceutical products and functional food. Lemon verbena (Lippia citriodora Kunth) has been traditionally used for respiratory, digestive, and muscular diseases, showing effects that are promoted by the antioxidant activity of its phytoconstituents. The antioxidant power of several lemon verbena extracts has been tested but its isolated compounds activity has not been described. The aim of the present work was to isolate phytochemicals from a commercial lemon verbena extract through a semi-preparative high-performance liquid chromatography approach for further evaluation of its individual antioxidant activity using three different methods. The structure-antioxidant activity relationships revealed the influence of substitutions in the strong antioxidant power exerted by glycosylated phenylpropanoids, in contrast to the low antioxidant capacity showed by iridoids. Development of enriched extracts in these compounds could lead to greater antioxidant effects and improved functional ingredients to prevent chronic diseases.

Antioxidant and Photoprotective Activity of Apigenin and its Potassium Salt Derivative in Human Keratinocytes and Absorption in Caco-2 Cell Monolayers.

Ultraviolet (UV) radiation, especially types A (UVA) and B (UVB), is one of the main causes of skin disorders, including photoaging and skin cancer. Ultraviolent radiation causes oxidative stress, inflammation, p53 induction, DNA damage, mutagenesis, and oxidation of various molecules such as lipids and proteins. In recent decades, the use of polyphenols as molecules with an antioxidant and anti-inflammatory capacity has increased. However, some of these compounds are poorly soluble, and information regarding their absorption and bioavailability is scarce. The main objective of this study was to compare the intestinal absorption and biological activity of apigenin and its more soluble potassium salt (apigenin-K) in terms of antioxidant and photoprotective capacity. Photoprotective effects against UVA and UVB radiation were studied in human keratinocytes, and antioxidant capacity was determined by different methods, including trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Finally, the intestinal absorption of both apigenins was determined using an in vitro Caco-2 cell model. Apigenin showed a slightly higher antioxidant capacity in antioxidant activity assays when compared with apigenin-K. However, no significant differences were obtained for their photoprotective capacities against UVA or UVB. Results indicated that both apigenins protected cell viability in approximately 50% at 5 J/m2 of UVA and 90% at 500 J/m2 of UVB radiation. Regarding intestinal absorption, both apigenins showed similar apparent permeabilities (Papp), 1.81 × 10-5 cm/s and 1.78 × 10-5 cm/s, respectively. Taken together, these results suggest that both apigenins may be interesting candidates for the development of oral (nutraceutical) and topical photoprotective ingredients against UVA and UVB-induced skin damage, but the increased water solubility of apigenin-K makes it the best candidate for further development.

Differential effects of a combination of Hibiscus sabdariffa and Lippia citriodora polyphenols in overweight/obese subjects: A randomized controlled trial.

Plant-polyphenols have shown the capacity to ameliorate obesity-induced metabolic disturbances, both in cell and animal models, where most therapeutic approaches have failed. On the basis of previous research, a dietary supplement containing 500 mg of a combination of polyphenolic extracts from Lippia citriodora L. and Hibiscus sabdariffa L. (LC-HS), in the context of an equilibrated isocaloric diet, was evaluated in a double blind, placebo-controlled and randomized trial in 56 obese/overweight subjects for two months. Compared to controls, the consumption of the LC-HS polyphenols showed significant improvements in body weight, abdominal circumference of overweight subjects (-6.79 ± 0.80 cm in overweight LC-HS group vs -1.85 ± 0.83 cm in controls, p < 0.001) and body fat % (-1.33 ± 0.15% in overweight LC-HS group vs -0.66 ± 0.17% in controls, p < 0.05). Heart rate and systolic blood pressure also presented significant improvements in overweight LC-HS participants. However, changes were more modest in obese subjects. Further, LC-HS extract significantly reduced lipid content and increased AMPK activity in a hypertrophied adipocyte cell model. Therefore, consumption of 500 mg/day of LC-HS extracts enriched in polyphenols for two months in the context of an isocaloric diet by overweight subjects decreased symptoms associated to obesity-related diseases. Modulation of fat metabolism in adipose tissue, probably mediated by AMPK activation, is proposed as a molecular target to be explored in future research.