Impact of Foods and Dietary Supplements Containing Hydroxycinnamic Acids on Cardiometabolic Biomarkers: A Systematic Review to Explore Inter-Individual Variability

Plant-based diets rich in bioactive compounds such as polyphenols have been shown to positively modulate the risk of cardiometabolic (CM) diseases. The inter-individual variability in the response to these bioactives may affect the findings. This systematic review aimed to summarize findings from existing randomized clinical trials (RCTs) evaluating the effect of hydroxycinnamic acids (HCAs) on markers of CM health in humans. Literature searches were performed in PubMed and the Web of Science. RCTs on acute and chronic supplementation of HCA-rich foods/extracts on CM biomarkers were included. Forty-four RCTs (21 acute and 23 chronic) met inclusion criteria. Comparisons were made between RCTs, including assessments based on population health status. Of the 44 RCTs, only seven performed analyses on a factor exploring inter-individual response to HCA consumption. Results demonstrated that health status is a potentially important effect modifier as RCTs with higher baseline cholesterol, blood pressure and glycaemia demonstrated greater overall effectiveness, which was also found in studies where specific subgroup analyses were performed. Thus, the effect of HCAs on CM risk factors may be greater in individuals at higher CM risk, although future studies in these populations are needed, including those on other potential determinants of inter-individual variability. PROSPERO, registration number CRD42016050790

Systematic bioinformatic analyses of nutrigenomic modifications by polyphenols associated with cardiometabolic health in humans: Evidence from targeted nutrigenomic studies

Cardiometabolic disorders are among the leading causes of mortality in the human population. Dietary polyphenols exert beneficial effects on cardiometabolic health in humans. Molecular mechanisms, however, are not completely understood. Aiming to conduct in-depth integrative bioinformatic analyses to elucidate molecular mechanisms underlying the protective effects of polyphenols on cardiometabolic health, we first conducted a systematic literature search to identify human intervention studies with polyphenols that demonstrate improvement of cardiometabolic risk factors in parallel with significant nutrigenomic effects. Applying the predefined inclusion criteria, we identified 58 differentially expressed genes at mRNA level and 5 miRNAs, analyzed in peripheral blood cells with RT-PCR methods. Subsequent integrative bioinformatic analyses demonstrated that polyphenols modulate genes that are mainly involved in the processes such as inflammation, lipid metabolism, and endothelial function. We also identified 37 transcription factors that are involved in the regulation of polyphenol modulated genes, including RELA/NFKB1, STAT1, JUN, or SIRT1. Integrative bioinformatic analysis of mRNA and miRNA-target pathways demonstrated several common enriched pathways that include MAPK signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, focal adhesion, or PPAR signaling pathway. These bioinformatic analyses represent a valuable source of information for the identification of molecular mechanisms underlying the beneficial health effects of polyphenols and potential target genes for future nutrigenetic studies

Epidemiological study and analysis of the biological role of edible plants and their natural products from the region of Thrace

Introduction: The use of natural products as therapeutic agents has been the subject of several scientific articles in recent years. Nowadays, the evolution of societies, science, and technology allow and encourage the search for healing resources through the "pharmacy of nature". Many Greek natural products have been studied in terms of their healing properties, while one of the first points of research interest was olive oil, as a primary component of the Mediterranean Diet and Greek - or ancient Greek - culture. In addition, also as elements of the Mediterranean Diet, many of the native medicinal and aromatic plants (MAPs) of our country have been studied, presenting important characteristics of biological activity, and expanding the knowledge that begins with folk medicine through evidence of experimental practice.Scope: This study aimed to find evidence of folk remedies through a nutritional epidemiological study in the region of Thrace and to substantiate the findings through experimental practice regarding the use of natural products and their biological action. In detail, an epidemiological study was conducted with a properly structured questionnaire on the use of natural products in the region of Thrace, including answers from adults from the regions of Evros, Xanthi, and Rodopi. In addition, the antioxidant and anti-inflammatory activity of natural extracts of oregano from the areas of Alexandroupolis and Samothrace were studied, using the locally produced olive oil as an extraction matrix. Methods: The research protocols included the qualitative and quantitative characterization of the components extracted by gas chromatography (HS-SPME GC/MS) and biochemical methods for the detection of phytochemical components of the samples. In detail, the protocols performed were: Folin-Ciocalteu for the determination of total phenolic content, total flavonoid content via the colorimetry assay, and the ability to interact with DPPH and ABTS radicals. Also, both as evidence of antioxidant capacity and as indicators of potential anti-inflammatory action, the ability to inhibit linoleic acid peroxidation (AAPH/LLA) and the ability to inhibit lipoxygenase (LOX) activity were studied. All the samples were also examined for cytotoxicity (MTT method) in macrophage cells (RAW264.7), in which the antioxidant activity was additionally studied as the ability to bind OH- radicals (Nash reaction) and NO radicals (Griess reaction) after H2O2 exposure and lipopolysaccharide (LPS), respectively.Results: The 561 respondents (age: 39.7 ± 11.6 years) were primarily female (59.7%), with higher education (69.8%), working as public or private employees (55.4 %), and had a low/middle income (77.1%). Overall, more than 70% used MAPs for various medical conditions, the most common being chamomile against the common cold and flu. More than 20 different MAPs were used at lower frequencies in multiple conditions. Key factors contributing to the consumption of MAPs were gender (female vs. male), employment (employed vs. unemployed), education (higher vs. less), and higher body mass index (overweight and obese vs. normal), while consumption of fruits, fish, and vegetables was mainly associated with the use of MAPs as common food items and in pathological conditions.This study also presents the preparation and evaluation of the antioxidant activity of a lesser-known variety of olive oil from the Makri region, located in Alexandroupolis (Thrace) Greece, infused with two samples of dried oregano, one also from Alexandroupolis and the other from the island of Samothrace. Regarding the evaluation of the antioxidant activity through the ABTS and DPPH methods, it is worth noting that in this test, the combination of OA and VOOL, regardless of the extraction method, has overall higher results than the combination of OS and VOOL. Furthermore, in the DPPH evaluation, there was a similar trend of the samples with respect to the extraction time, which could also be related to the previous findings on the total phenolic content of the samples. In this context, the relationship between phenolic content and antioxidant potential is reported in previous literature, particularly for the evaluation of olive oil. A similar trend was observed in the study of the ability to inhibit the oxidation of linoleic acid, with the effect of the extraction time being more evident in the natural extraction samples. Regarding lipoxygenase inhibition capacity, little capacity was recorded for all samples while the preparation method had no significant effect. In addition, no toxicity of the examined samples was recorded in RAW264.7 cells, in which, however, an ability to bind OH and NO radicals was recorded, with the latter showing significant differences regarding the preparation method (in favor of natural extraction).Conclusions: The use of MAPs as part of the diet and as an element of therapeutic use is present in the examined population, while particular choices seem to be influenced by socioeconomic and lifestyle factors. Regarding the in vitro evaluation of the biological role of the samples in this study, it should be noted that a similar evaluation of the combined effects of these products is rare in the current literature. The results showed that ultrasonic extraction was beneficial for the total antioxidant profile of the final product, which was time-dependent, with 5-7 minutes being the most appropriate. Similarly, natural extraction had the best results at 10-20 days. Differences in the oregano samples were present but not decisive for the results. The two extraction methods had equally satisfactory results in all of the protocols evaluated with natural extraction being in the lead, up to a small degree. Further studies would be necessary to understand better the nutritional and biological contribution of these natural products and their combination in antioxidant protection.Εισαγωγή: Η χρήση των φυσικών προϊόντων ως θεραπευτικοί παράγοντες, έχει αποτελέσει αντικείμενο μελέτης για μια πλειάδα επιστημονικών αντικειμένων κατά τα τελευταία έτη. Σήμερα, η εξέλιξη των κοινωνιών, της επιστήμης και της τεχνολογίας επιτρέπουν και ενθαρρύνουν την αναζήτηση θεραπευτικών πηγών μέσα από το «φαρμακείο της φύσης». Πλήθος φυσικών προϊόντων έχουν μελετηθεί από τον Ελλαδικό χώρο ως προς τις θεραπευτικές τους ιδιότητες, ενώ από τα πρώτα σημεία ερευνητικού ενδιαφέροντος αποτέλεσε το ελαιόλαδο ως πρωτεύων συστατικό της Μεσογειακής Διατροφής αλλά και της Ελληνικής – ή και αρχαιοελληνικής κουλτούρας. Επιπλέον, επίσης ως στοιχεία της Μεσογειακής Διατροφής, έχουν μελετηθεί πολλά από τα αυτοφυή αρωματικά και φαρμακευτικά φυτά (ΑΦΦ) της χώρας μας, παρουσιάζοντας σημαντικά χαρακτηριστικά βιολογικής δραστικότητας και στοιχειοθετώντας εξελικτικά μέσα από την πειραματική πράξη, γνώσεις οι οποίες ξεκινούν από την λαϊκή θεραπευτική.Σκοπός της παρούσας μελέτης ήταν η εύρεση στοιχείων λαϊκής θεραπευτικής μέσα από μία διατροφική επιδημιολογική μελέτη στην περιοχή της Θράκης και η στοιχειοθέτηση των ευρημάτων μέσα από την πειραματική πράξη, αναφορικά με την χρήση φυσικών προϊόντων και την βιολογική τους δράση. Μεθοδολογία: Αναλυτικά, πραγματοποιήθηκε επιδημιολογική μελέτη με κατάλληλα δομημένο ερωτηματολόγιο, για την χρήση των φυσικών προϊόντων στην περιοχή της Θράκης συμπεριλαμβάνοντας απαντήσεις ενηλίκων από τις περιοχές του Έβρου, της Ξάνθης και της Ροδόπης. Επιπλέον, μελετήθηκε η αντιοξειδωτική, και αντιφλεγμονώδης δράση φυσικών εκχυλισμάτων αυτοφυούς ρίγανης από τις περιοχές της Αλεξανδρούπολης (ΟΑ) και της Σαμοθράκης (OS) οι οποίες εκχυλίστηκαν σε ελαιόλαδο (VOOL) και αγουρέλαιο (GOO) ποικιλίας «Μάκρης». Τα ερευνητικά πρωτόκολλα συμπεριλάμβαναν τον ποιοτικό και ποσοτικό χαρακτηρισμό των συστατικών που εκχυλίστηκαν με μεθόδους αέριας χρωματογραφίας (HS-SPME GC/MS) και βιοχημικών μεθόδων ανίχνευσης των φυτοχημικών συστατικών των δειγμάτων. Αναλυτικά, πραγματοποιήθηκαν πρωτόκολλα για τον προσδιορισμό του συνολικού φαινολικού περιεχομένου και των συνολικών φλαβονοειδών, καθώς επίσης μελέτη της αντιοξειδωτικής δράσης ως ικανότητα αλληλεπίδρασης με τις ρίζες DPPH και ABTS. Επίσης, τόσο ως στοιχεία αντιοξειδωτικής ικανότητας όσο και ως δείκτες πιθανής αντιφλεγμονώδους δράσης, μελετήθηκε η ικανότητα αναστολής της υπεροξείδωσης του λινελαϊκού οξέος (AAPH/LLA) και η ικανότητα αναστολής της δράσης της λιποξυγονάσης (LOX). Στο σύνολο των δειγμάτων εξετάστηκε επίσης η βιωσιμότητα (μέθοδος ΜΤΤ) σε μακροφάγα κύτταρα (RAW264.7), στα οποία μελετήθηκαν επιπλέον η αντιοξειδωτική δράση ως ικανότητα δέσμευσης ριζών ΟΗ- (αντίδραση Nash) και ριζών ΝΟ (αντίδραση Griess) έπειτα από την επίδραση Η2Ο2 και λιποπολυσακχαρίτη (LPS), αντίστοιχα. Αποτελέσματα: Οι 561 ερωτηθέντες (ηλικία: 39,7 ± 11,6 ετών) ήταν ως επί το πλείστων γυναίκες (59,7%), με ανώτερη εκπαίδευση (69,8%), εργάζονταν ως δημόσιοι ή ιδιωτικοί υπάλληλοι (55,4%) και είχαν χαμηλό/μεσαίο εισόδημα (77,1%). Συνολικά, περισσότερο από το 70% χρησιμοποιούσε ΑΦΦ σε διάφορες παθολογικές καταστάσεις, πιο συχνά χαμομήλι κατά του κοινού κρυολογήματος και της γρίπης. Περισσότερα από 20 διαφορετικά ΑΦΦ χρησιμοποιήθηκαν σε μικρότερες συχνότητες σε διάφορες συνθήκες. Βασικοί παράγοντες που συνέβαλαν στην κατανάλωση των ΑΦΦ ήταν το φύλο (γυναίκα έναντι ανδρών), η απασχόληση (απασχολούμενη έναντι ανέργων), η εκπαίδευση (τριτοβάθμια εκπαίδευση έναντι χαμηλότερης) και ο υψηλότερος δείκτης μάζας σώματος (υπέρβαροι και παχύσαρκοι έναντι φυσιολογικού), ενώ η κατανάλωση σε φρούτα, ψάρια και τα λαχανικά συνδέθηκαν κυρίως με τη χρήση των ΑΦΦ ως κοινών ειδών διατροφής και σε παθολογικές καταστάσεις.Στη μελέτη αυτή παρουσιάζεται επίσης η παρασκευή και η αξιολόγηση της αντιοξειδωτικής δράσης μιας λιγότερο γνωστής ποικιλίας ελαιολάδου από την περιοχή της Μάκρης, που βρίσκεται στην Αλεξανδρούπολη (Θράκη) Ελλάδας, εμποτισμένης με δύο δείγματα αποξηραμένης ρίγανης, το ένα επίσης από την Αλεξανδρούπολη και το άλλο από το νησί της Σαμοθράκης. Όσον αφορά την αξιολόγηση της αντιοξειδωτικής δράσης μέσω των μεθόδων ABTS και DPPH, αξίζει να σημειωθεί ότι σε αυτή τη δοκιμασία, ο συνδυασμός ΟΑ και VOOL, ανεξάρτητα από τη μέθοδο εκχύλισης, έχει συνολικά υψηλότερα αποτελέσματα σε σχέση με τον συνδυασμό OS και VOOL. Επιπλέον, στην αξιολόγηση DPPH υπήρξε παρόμοια τάση των δειγμάτων ως προς τον χρόνο εκχύλισης, η οποία θα μπορούσε επίσης να σχετίζεται με τα προηγούμενα ευρήματα σχετικά με τη συνολική περιεκτικότητα των δειγμάτων σε φαινολικά. Σε αυτό το πλαίσιο, η σχέση μεταξύ της περιεκτικότητας σε φαινολικά και του αντιοξειδωτικού δυναμικού αναφέρεται σε προηγούμενη βιβλιογραφία, ιδιαίτερα για την αξιολόγηση του ελαιολάδου. Παρόμοια τάση παρατηρήθηκε και στην μελέτη ικανότητας αναστολής της οξείδωσης του λινελαϊκού οξέος, με πιο εμφανή την επίδραση του χρόνου εκχύλισης στα δείγματα της φυσικής εκχύλισης. Αναφορικά με την ικανότητα αναστολής της λιποξυγονάσης, καταγράφηκε μικρή ικανότητα για το σύνολο των δειγμάτων ενώ η μέθοδος παρασκευής δεν είχε σημαντική επίδραση. Επιπλέον, δεν καταγράφηκε τοξικότητα των εξεταζόμενων δειγμάτων, σε κύτταρα RAW264.7, στα οποία ωστόσο καταγράφηκε ικανότητα δέσμευσης ριζών ΟΗ και ΝΟ, με την δεύτερη να παρουσιάζει σημαντικές διαφορές αναφορικά με την μέθοδο παρασκευής (προς όφελος της φυσικής εκχύλισης). Συμπεράσματα: Η χρήση των ΑΦΦ ως μέρος της διατροφής και ως στοιχείο θεραπευτικής χρήσης, είναι παρούσα στον εξεταζόμενο πληθυσμό, ενώ ιδιαίτερες επιλογές φαίνεται να επηρεάζονται από κοινωνικόοικονομικούς παράγοντες και παράγοντες του τρόπου ζωής. Όσον αφορά την in vitro αξιολόγηση του βιολογικού ρόλου των δειγμάτων αυτής της μελέτης, θα πρέπει να σημειωθεί ότι παρόμοια αξιολόγηση των συνδυασμένων επιδράσεων αυτών των προϊόντων είναι σπάνια στην τρέχουσα βιβλιογραφία. Τα αποτελέσματα έδειξαν ότι η εκχύλιση με υπερήχους ήταν ευεργετική για το συνολικό αντιοξειδωτικό προφίλ του τελικού προϊόντος, το οποίο εξαρτάται από το χρόνο, με καταλληλότερο τα 5-7 λεπτά. Παρομοίως, η φυσική εκχύλιση είχε τα καλύτερα αποτελέσματα στις 10-20 ημέρες. Διαφορές στα δείγματα ρίγανης ήταν παρούσες αλλά όχι καθοριστικές για τα αποτελέσματα. Οι δύο μέθοδοι εκχύλισης είχαν εξίσου ικανοποιητικά αποτελέσματα στο σύνολο των πρωτοκόλλων που αξιολογήθηκαν με την φυσική εκχύλιση να προηγείται σε ένα μικρό βαθμό. Περαιτέρω μελέτες θα ήταν απαραίτητες για την καλύτερη κατανόηση της διατροφικής και βιολογικής συμβολής αυτών των φυσικών προϊόντων και του συνδυασμού τους στην αντιοξειδωτική προστασία

Natural Functional Foods as a Part of the Mediterranean Lifestyle and Their Association with Psychological Resilience and Other Health-Related Parameters

Natural Functional Foods (NFFs) are unprocessed foods with proven health benefits beyond their nutritional value. The Mediterranean Diet (MD) and Mediterranean Lifestyle (MEDILIFE) are well known for their beneficial effects on health. Psychological Resilience (PsyR) is not only an important factor in human well-being; it is also regarded as a key indicator of mental health. The purpose of this study was to explore the relationship between NFFs and the MD and MEDILIFE in Greece, as well as their association with PsyR and other health-related parameters. In a cross-sectional design, 338 healthy adults participated voluntarily in an online research survey. There was a statistically significant association between the consumption of NFFs grown and produced in the Mediterranean region and the MD and MEDILIFE (p p p p p p < 0.01 compared with no weight loss). This study identified NFFs as a part of the MD and MEDILIFE. NFFs linked to the MEDILIFE could help predict the outcome of a weight loss diet and appear to have a positive effect on PsyR, sleep quality, and maintaining a healthy weight. Thus, the consumption of NFFs grown and produced in the Mediterranean region could be a natural, healthy, and sustainable way of enhancing physical–mental health. Randomised controlled trials should be conducted to confirm the findings of this cross-sectional study

The Role of Natural Products in Rheumatoid Arthritis: Current Knowledge of Basic In Vitro and In Vivo Research

Rheumatoid arthritis (RA) is an autoimmune disorder affecting a vast variety of the population. The onset of RA as well as the development of systematic immunization is affected by both genetic and environmental risk factors. This review aims to point out the role of natural products in the management of RA, focusing on the reports of basic research (in vitro and animal studies) emphasizing the antioxidant and anti-inflammatory properties considered in the field of RA. A systematic screening of the relevant literature was carried out on PubMed, Google Scholar, and Scopus with the following criteria: publication date, 2015–2020; language, English; study design, in vitro or animal models; and the investigation of one or several natural products in the context of RA, including, when available, the molecular mechanisms implicated. A total of 211 papers were initially obtained and screened. In vitro and animal studies referring to 20 natural products and 15 pure compounds were ultimately included in this review. The outcomes of this work provide an overview of the methods employed in basic research over the past five years, with emphasis on the limitations presented, while demonstrating the potential benefits of utilizing natural products in the management of RA as supported by in vitro and animal studies

Novel Pyrimidine Derivatives as Antioxidant and Anticancer Agents: Design, Synthesis and Molecular Modeling Studies

The heterocyclic ring system of pyrido [2,3-d]pyrimidines is a privileged scaffold in medicinal chemistry, possessing several biological activities. The synthesis of the pyrimidine derivatives was performed via the condensation of a suitable α,β-unsaturated ketone with 4-amino-6-hydroxy-2-mercaptopyrimidine monohydrate in glacial acetic acid. Chalcones were synthesized, as starting materials, via the Claisen–Schmidt condensation of an appropriately substituted ketone and an appropriately substituted aldehyde in the presence of aqueous KOH 40% w/v in ethanol. All the synthesized compounds were characterized using IR, 1H-NMR, 13C-NMR, LC-MS and elemental analysis. The synthesized compounds were evaluated for their antioxidant (DPPH assay), anti-lipid peroxidation (AAPH), anti-LOX activities and ability to interact with glutathione. The compounds do not interact significantly with DPPH but strongly inhibit lipid peroxidation. Pyrimidine derivatives 2a (IC50 = 42 μΜ), 2f (IC50 = 47.5 μΜ) and chalcone 1g (IC50 = 17 μM) were the most potent lipoxygenase inhibitors. All the tested compounds were found to interact with glutathione, apart from 1h. Cell viability and cytotoxicity assays were performed with the HaCaT and A549 cell lines, respectively. In the MTT assay towards the HaCaT cell line, none of the compounds presented viability at 100 μM. On the contrary, in the MTT assay towards the A549 cell line, the tested compounds showed strong cytotoxicity at 100 μM, with derivative 2d presenting the strongest cytotoxic effects at the concentration of 50 μΜ

Unraveling Natural Products’ Role in Osteoarthritis Management—An Overview

The natural process of aging gradually causes changes in living organisms, leading to the deterioration of organs, tissues, and cells. In the case of osteoarthritis (OA), the degradation of cartilage is a result of both mechanical stress and biochemical factors. Natural products have already been evaluated for their potential role in the prevention and treatment of OA, providing a safe and effective adjunctive therapeutic approach. This review aimed to assess the therapeutic potential of natural products and their derivatives in osteoarthritis via a systematic search of literature after 2008, including in vitro, in vivo, ex vivo, and animal models, along with clinical trials and meta-analysis. Overall, 170 papers were obtained and screened. Here, we presented findings referring to the preventative and therapeutic potential of 17 natural products and 14 naturally occurring compounds, underlining, when available, the mechanisms implicated. The nature of OA calls to initially focus on the management of symptoms, and, in that context, several naturally occurring compounds have been utilized. Underlying a global need for more sustainable natural sources for treatment, the evidence supporting their chondroprotective potential is still building up. However, arriving at that kind of solution requires more clinical research, targeting the implications of long-term treatment, adverse effects, and epigenetic implications

Olive oil consumption, as an indicator of Mediterranean diet adherence, is not education level-related in North Macedonia

The consumption of olive oil is one of the hallmarks of the Mediterranean diet (MD). Being rich in polyphenols, olive oil is considered to underlie, at least in part, the much appreciated positive influence of MD on health preservation and longevity. The work presented here is a part of a larger project, MeDiWeB (Mediterranean Diet and Wellbeing), conducted using an on-line questionnaire. One of the goals of the Project is to study the adherence to the MD among the citizens of North Macedonia, as a sub-Mediterranean country. The aim of the present work was to study the association between the education level of the participants and the amount of the consumed olive oil per day; therefore, only data obtained from these questions have been analyzed and presented here. Our results demonstrate that in general, the citizens of North Macedonia do not use the olive oil as a main cooking oil, and have a low amount of olive oil intake on a daily basis. This result was expected, since sunflower oil is used traditionally for cooking purposes. The results also demonstrate lack of association between the level of participants’ education and olive oil intake. It is expected that further analyses of the data collected with the MeDiWeB questionnaire will give a deeper understanding of the reasons for the low intake of olive oil in North Macedonia. In order to increase the olive oil intake, the general population can be more informed about the health benefits of regular olive oil consumption

Synthesis, Bioactivity, Pharmacokinetic and Biomimetic Properties of Multi-Substituted Coumarin Derivatives

A series of novel multi-substituted coumarin derivatives were synthesized, spectroscopically characterized, and evaluated for their antioxidant activity, soybean lipoxygenase (LOX) inhibitory ability, their influence on cell viability in immortalized human keratinocytes (HaCaT), and cytotoxicity in adenocarcinomic human alveolar basal epithelial cells (A549) and human melanoma (A375) cells, in vitro. Coumarin analogues 4a–4f, bearing a hydroxyl group at position 5 of the coumarin scaffold and halogen substituents at the 3-phenyl ring, were the most promising ABTS•+ scavengers. 6,8-Dibromo-3-(4-hydroxyphenyl)-4-methyl-chromen-2-one (4k) and 6-bromo-3-(4,5-diacetyloxyphenyl)-4-methyl-chromen-2-one (3m) exhibited significant lipid peroxidation inhibitory activity (IC50 36.9 and 37.1 μM). In the DCF-DA assay, the 4′-fluoro-substituted compound 3f (100%), and the 6-bromo substituted compounds 3i (80.9%) and 4i (100%) presented the highest activity. The 3′-fluoro-substituted coumarins 3e and 4e, along with 3-(4-acetyloxyphenyl)-6,8-dibromo-4-methyl-chromen-2-one (3k), were the most potent lipoxygenase (LOX) inhibitors (IC50 11.4, 4.1, and 8.7 μM, respectively) while displaying remarkable hydroxyl radical scavenging ability, 85.2%, 100%, and 92.9%, respectively. In silico docking studies of compounds 4e and 3k, revealed that they present allosteric interactions with the enzyme. The majority of the analogues (100 μΜ) did not affect the cell viability of HaCaT cells, though several compounds presented over 60% cytotoxicity in A549 or A375 cells. Finally, the human oral absorption (%HOA) and plasma protein binding (%PPB) properties of the synthesized coumarins were also estimated using biomimetic chromatography, and all compounds presented high %HOA (&gt;99%) and %PPB (60–97%) values