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Phenolic compounds from marine organisms are far less studied than those from terrestrial sources since their structural diversity and variability require powerful analytical tools. However, both their biological relevance and potential properties make them an attractive group deserving increasing scientific interest. The use of efficient extraction and, in some cases, purification techniques can provide novel bioactives useful for food, nutraceutical, cosmeceutical and pharmaceutical applications. The bioactivity of marine phenolics is the consequence of their enzyme inhibitory effect and antimicrobial, antiviral, anticancer, antidiabetic, antioxidant, or anti-inflammatory activities. This review presents a survey of the major types of phenolic compounds found in marine sources, as well as their reputed effect in relation to the occurrence of dietary and lifestyle-related diseases, notably type 2 diabetes mellitus, obesity, metabolic syndrome, cancer and Alzheimer’s disease. In addition, the influence of marine phenolics on gut microbiota and other pathologies is also addressed.

In many cocoa intervention studies, health outcomes are related to cocoa components without taking into account the bioavailability of the main bioactive components: phenolic compounds and methylxanthines. The present work associates the results of bioavailability and randomised controlled crossover studies in humans carried out with similar cocoa products, so that the main phenol and methylxanthine metabolites observed in plasma and urine are associated to the health effects observed in the chronic studies. We outstand that doses of cocoa and consumption rate used are realistic. In the bioavailability study, a conventional (CC) and a methylxanthine-polyphenol rich (MPC) cocoa product were used, whereas in the chronic study a dietary fibre-rich (DFC) and a polyphenol-rich (PC) product were studied in healthy and cardiovascular risk subjects. The main phenolic metabolites formed after CC and MPC intake, 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-sulfate, 3'-methyl-epicatechin-5-sulfate, 4-hydroxy-5-(4'-hydroxyphenyl)valeric acid-sulfate, 5-phenyl-γ-valerolactone--sulfate and 5-(4'-hydroxyphenyl)-γ-valerolactone-3'-glucuronide, may contribute to the changes in cholesterol (and indirectly HDL-cholesterol) observed after the regular intake of both DFC and PC, in healthy and cardiovascular risk subjects, whereas 7-methylxanthine (the main cocoa methylxanthine metabolite) and theobromine, together with its content in insoluble dietary fibre, may be responsible for the decrease of IL-1β and hypoglycemic effects observed with DFC. With both phenolic and methylxanthine metabolites a strong dose-response effect was observed. After the regular consumption of both DFC and PC, positive changes were observed in volunteer's lipid profile, which may be related to the long-lasting presence of colonic phenolic metabolites in blood. In contrast, the anti-inflammatory and hypoglycemic effects were only observed with DFC, and these may be related to methylxanthine metabolites, and it is likely that insoluble dietary fibre may have also played a role.

Background/Objectives: Loquat (Eriobotrya japonica) is widely cultivated for its fruit, while its aerial by-products remain largely underexploited despite increasing interest in plant-derived bioactive compounds and sustainable food systems. This study comprehensively investigates and compares the phenolic composition and in vitro bioactivities of loquat leaves and flowers to support their potential valorisation as functional ingredients. Methods: Extractable and non-extractable polyphenolic fractions were obtained and quantified, and the extractable fraction was further characterised using HPLC-ESI-QTOF-MS. In vitro bioactivity assessment included antioxidant capacity (FRAP and ABTS), glucose dialysis retardation index, and α-glucosidase inhibition. Results: Flowers contained significantly higher levels of both extractable and non-extractable polyphenols than leaves. Qualitative and semi-quantitative phenolic profiling, including multivariate analysis, revealed clear compositional differences between the two organs. Flowers showed a higher relative abundance of phenolic acids, as well as the presence of several compounds absent in leaves, such as kaempferol, naringenin-3-O-glucoside, and three glycosilated anthocyanins. Flower-derived fractions exhibited consistently higher antioxidant activity across all phenolic fractions than leaf-derived fractions, in agreement with their greater polyphenol content. Regarding antidiabetic activity, leaf samples showed a modest capacity to delay glucose diffusion, whereas this effect was not observed in flowers. In contrast, flower extracts displayed a strong inhibitory effect against α-glucosidase, exceeding that of the reference inhibitor acarbose, while this activity was not detectable in leaf extracts under the experimental conditions. Conclusions: These findings support the revalorisation of loquat by-products, particularly flowers, as sustainable sources of bioactive compounds with potential applications in functional foods and health-related products.

Hydroxytyrosol (HT) is a major phenolic compound in olives and extra virgin olive oil (EVOO), known for its antioxidant, anti-inflammatory, and cardiometabolic properties. The European Food Safety Authority (EFSA) has approved a health claim for the protection of LDL particles from oxidative damage only when HT is consumed within EVOO, which limits its direct use in supplements or functional foods. Since its biological effects depend on absorption, distribution, metabolism, and excretion (ADME), understanding how formulation and delivery strategies influence bioavailability is essential. HT is mainly present as secoiridoid derivatives in EVOO, whereas in supplements, it often appears in its free form, potentially affecting its metabolic fate. This review summarizes human studies on HT bioavailability from EVOO, isolated supplements, and enriched foods, and examines how matrix type, chemical modifications of HT, and advanced delivery systems, such as emulsions, encapsulation, and vesicular carriers, modulate absorption and metabolism. The gut microbiota is highlighted as an emerging factor in HT biotransformation, although its role remains underexplored. Further well-designed human studies are needed to guide the development of nutraceutical formulations capable of replicating the health benefits of EVOO beyond its natural matrix.

Hydroxytyrosol (HT), the primary phenolic compound in virgin olive oil, has notable cardiovascular benefits, particularly in preventing low-density lipoprotein (LDL) oxidation. However, its hydrophilicity limits its solubility and integration into lipid-based formulations. This study aimed to enhance its lipophilicity by synthesizing hydroxytyrosyl eicosapentaenoate (HT-EPA), a derivative of HT and eicosapentaenoic acid (EPA), using a one-step enzymatic catalysis with lipase B from Candida antarctica (CALB). The reaction, performed as a suspension of HT in ethyl eicosapentaenoate (Et-EPA) (1:9 molar ratio) under vacuum, achieved higher yields and shorter reaction times than previously reported, with a purity exceeding 98%, confirmed by 1H-NMR. For the first time, the antioxidant capacity of HT-EPA in comparison with other natural antioxidants was assessed using the FRAP assay, while its oxidative stability in an omega-3-rich oil matrix was evaluated via the Rancimat method. HT-EPA and hydroxytyrosyl acetate (HT-Ac) displayed antioxidant activity comparable to HT but significantly higher than α-tocopherol, a common food antioxidant. Given the scarcity of effective lipid-soluble antioxidants, HT-EPA represents a promising candidate for omega-3 nutraceuticals, offering enhanced stability and potential health benefits. This study provides a simple, efficient, and scalable strategy for developing functional lipid-based formulations with cardioprotective potential by improving HT solubility while preserving its antioxidant properties.

Biliary tract tumours, including bile duct, gallbladder, and ampulla of Vater malignancies, pose a rare but formidable oncologic challenge. Typically diagnosed at advanced stages, these tumours offer limited treatment options and dismal prognoses, with a five-year survival rate below 20%. First-line chemotherapy with gemcitabine-cisplatin has demonstrated only modest efficacy, leaving a pressing need for improved therapeutic strategies. This comprehensive review provides a detailed examination of the current landscape of second-line chemotherapy for biliary tract tumours. The pivotal ABC-06 trial established FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as the standard second-line therapy, demonstrating improved overall survival compared to active symptom control alone. Conversely, the NIFTY trial introduced nal-IRI (nanoliposomal irinotecan) plus 5-FU/LV (5-fluorouracil and leucovorin) as an alternative option, demonstrating substantial gains in progression-free and overall survival. However, the posterior NALIRICC trial presented conflicting results, raising questions about the added benefit of nal-IRI. Challenges in delivering second-line chemotherapy include rapid patient performance deterioration post-first-line treatment and limited access to second-line therapy. Only a fraction of eligible patients receive second-line therapy, emphasising the need for more effective first-line therapies to maintain patient fitness. The role of monotherapy in the second-line setting remains uncertain, particularly in unfit patients, and the absence of biomarkers for tailored treatment underscores the need for ongoing research. While challenges persist, ongoing investigations offer hope for optimising second-line therapy for biliary tract tumours, promising improved outcomes for patients facing this disease. This review provides an overview of current facts and challenges when delivering second-line chemotherapy for advanced biliary tract tumours.

The valorization of agricultural residues assumes a pivotal position in the circular economy by transforming waste into a useful and environmentally friendly product, with the cultivation of corn, as one of the world’s predominant crops, being crucial. This article aimed to investigate the feasibility of using residues from corn crop as biofuels, going more in-depth into determining the effect that crop variety may have on its thermal qualities. Specifically, 12 samples of corn crop residues were studied in three main groups: conventional, forage, and transgenic varieties. To achieve this, proximate and ultimate analyses, thermogravimetric analyses, and differential scanning calorimetry were conducted, along with a study of gas emissions and a statistical comparison of different varieties. From the results obtained, it is worth highlighting the low ash content in all the samples (between 5.55% and 8.42%) and high calorific values (higher than 17 MJ/kg in all cases), as well as optimal thermal results for all the samples studied in both pyrolysis and combustion processes. Significant differences were found between the different varieties; in particular, it was observed that the forage variety presented more optimal conditions for its application in both processes. This may represent a potential competitive advantage for the forage varieties.

Background: Hydroxytyrosol (HT) is a phenolic compound found in extra virgin olive oil that modulates oxidative and inflammatory status. However, clinical trials evaluating HT as a stand-alone supplement remain scarce, and its underlying mechanisms and pathway modulation are not yet fully understood. This study aimed to investigate the metabolic effects of HT supplementation in individuals with overweight and prediabetes using an untargeted metabolomics approach. Methods: An untargeted liquid chromatography–mass spectrometry (LC–MS)-based metabolomics analysis was performed on serum samples from 49 participants with overweight and prediabetes enrolled in a randomized controlled trial. Participants received either HT (15 mg/day for 16 weeks; n = 24) or placebo (n = 25). Global metabolomic profiling was used to compare metabolic changes between the two groups. Results: HT supplementation induced a distinct metabolic profile compared with placebo. Participants in the HT group showed reduced levels of nitrogenous base derivatives and arachidonic acid, together with increased concentrations of phosphatidylcholines, lysophosphatidylcholines and sphingomyelins. These alterations suggest modulation of two key metabolic pathways including purine degradation and arachidonic acid metabolism. Conclusions: These findings provide mechanistic insights into the biological effects of HT and support the integration of metabolomics and multi-omics approaches in future clinical studies to validate these pathways in larger populations.

Brunfelsia grandiflora is an ancient plant widely used for its promising medicinal properties, although little explored scientifically. Despite being a rich source of phenolic compounds responsible in part for the proven anti-inflammatory activity, its characterization has not been carried out to date. The present work deals with the exhaustive identification and quantification of its phenolic fraction, along with its antioxidant activity. Decoction resulting from the bark as fine powder was filtered and lyophilized, and polyphenols were extracted from the resulting product by aqueous-organic solvents. Seventy-nine polyphenols were identified using LC-MSn. Hydroxycinnamates was the most abundant group of compounds (up to 66.8%), followed by hydroxycoumarins (15.5%), lignans (6.1%), flavonols (5.7%), phenolic simples (3.1), gallates (2.3%), flavanols (0.3%), and flavanones (0.2%). About 64% of the characterized phenols were in their glycosylated forms. The quantification of these phytochemicals by LC-QToF showed that this medicinal plant contained 2014.71 mg of phenolic compounds in 100 g dry matter, which evidences a great antioxidant potency determined by ABTS and DPPH assays. Therefore, Brunfelsia grandiflora represents an important source of polyphenols which supports its therapeutic properties scientifically proven.

Cocoa products present great health potential due to their high content of polyphenols, mainly of flavanols. However, the antioxidant, anti-inflammatory and other health effects of regularly consuming cocoa products seem to depend on the intake and health status of the consumer, etc. and need to be further clarified. A randomised, controlled, cross-over, free-living study was carried out in healthy (n 24) and moderately hypercholesterolaemic (>2000 mg/l, n 20) subjects to assess the influence of regularly consuming (4 weeks) two servings (15 g each) of a cocoa product rich in fibre (containing 33·9 % of total dietary fibre (TDF) and 13·9 mg/g of soluble polyphenols) in milk v. consuming only milk (control) on (1) serum lipid and lipoprotein profile, (2) serum malondialdehyde levels, carbonyl groups, ferric reducing/antioxidant power, oxygen radical absorbance capacity and free radical-scavenging capacity, (3) IL-1β, IL-6, TNF-α, IL-10, IL-8, monocyte chemoattractant protein-1, and vascular and intracellular cell adhesion molecule levels, and (4) systolic and diastolic blood pressure and heart rate. Throughout the study, the diet and physical activity of the volunteers, as well as any possible changes in weight or other anthropometric parameters, were also evaluated. The intake of TDF increased (P< 0·001) to the recommended levels. Serum HDL-cholesterol (HDL-C) levels were increased (P< 0·001), whereas glucose (P= 0·029), IL-1β (P= 0·001) and IL-10 (P= 0·001) levels were decreased. The rest of the studied cardiovascular parameters, as well as the anthropometric ones, remained similar. In conclusion, regularly consuming a cocoa product with milk improves cardiovascular health by increasing HDL-C levels and inducing hypoglycaemic and anti-inflammatory effects in healthy and hypercholesterolaemic individuals without causing weight gain.