Antioxidant, Antitumoral, Antimicrobial, and Prebiotic Activity of Magnetite Nanoparticles Loaded with Bee Pollen/Bee Bread Extracts and 5-Fluorouracil.

The gut microbiota dysbiosis that often occurs in cancer therapy requires more efficient treatment options to be developed. In this concern, the present research approach is to develop drug delivery systems based on magnetite nanoparticles (MNPs) as nanocarriers for bioactive compounds. First, MNPs were synthesized through the spraying-assisted coprecipitation method, followed by loading bee pollen or bee bread extracts and an antitumoral drug (5-fluorouracil/5-FU). The loaded-MNPs were morphologically and structurally characterized through transmission electron microscopy (TEM), selected area electron diffraction (SAED), scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Dynamic Light Scattering (DLS), and thermogravimetric analysis. UV-Vis spectroscopy was applied to establish the release profiles and antioxidant activity. Furthermore, the antibacterial and antitumoral activity of loaded-MNPs was assessed. The results demonstrate that MNPs with antioxidant, antibacterial, antiproliferative, and prebiotic properties are obtained. Moreover, the data highlight the improvement of 5-FU antibacterial activity by loading on the MNPs' surface and the synergistic effects between the anticancer drug and phenolic compounds (PCs). In addition, the prolonged release behavior of PCs for many hours (70-75 h) after the release of 5-FU from the developed nanocarriers is an advantage, at least from the point of view of the antioxidant activity of PCs. Considering the enhancement of L. rhamnosus MF9 growth and antitumoral activity, this study developed promising drug delivery alternatives for colorectal cancer therapy.

Natural Bioactive Compounds and Human Health.

Natural bioactive compounds encompass a vast array of molecules derived from plants, fungi, marine organisms, and other natural sources [...].

Comprehensive Analysis of Novel Synergistic Antioxidant Formulations: Insights into Pharmacotechnical, Physical, Chemical, and Antioxidant Properties.

(1) Background: Oxidative stress plays a pivotal role in the pathogenesis of various diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and diabetes, highlighting the pressing need for effective antioxidant interventions. (2) Methods: In this study, we aimed to develop and characterise two novel antioxidant formulations, F3 and F4, as therapeutic interventions for oxidative stress-related conditions. (3) Results: The physicochemical characterisation, preformulation analysis, formulation, preparation of filling powders for capsules, capsule content evaluation, and antioxidant activity assessment of the two novel antioxidant formulations were assessed. These formulations comprise a combination of well-established antioxidants like quercetin, biotin, coenzyme Q10, and resveratrol. Through comprehensive testing, the formulations' antioxidant efficacy, stability, and potential synergistic interactions were evaluated. (4) Conclusions: The findings underscore the promising potential of these formulations as therapeutic interventions for oxidative stress-related disorders and highlight the significance of antioxidant interventions in mitigating their progression.

Assessment of Dietary and Lifestyle Quality among the Romanian Population in the Post-Pandemic Period.

BACKGROUND: The pandemic caused by the SARS-CoV-2 virus demonstrated the importance of prevention through a healthy diet and lifestyle, the most vulnerable people being those with severe chronic conditions, those who are overweight, and those with an unbalanced immune system. This study aims to examine the nutritional status and lifestyle behaviors of the Romanian population. METHODS: The evaluation of the eating habits and lifestyle of the Romanian population in the post-pandemic period was carried out based on a cross-sectional observational study with the help of a questionnaire. RESULTS: A total of 4704 valid answers were registered (3136 female and 1568 male respondents). Among the respondents, most of them belong to the young population, 2892 between the ages of 18 and 40, i.e., 61.5%. Most male respondents are overweight (1400) and obese (780). Most respondents indicated a tendency to consume 1-2 meals per day irregularly (p = 0.617). Only 974 respondents adopted a healthy diet, and 578 a healthy lifestyle. CONCLUSIONS: The present study reports low adherence to a healthy diet (20.7%) and healthy lifestyle (12.28%), especially among the young population (<30 years). In the current context, it reports a reduced tendency to consume vegetables and fruits among the population, below the daily average recommended by the nutrition guidelines, a tendency towards sedentary behavior, and even deficient hydration of some of the respondents; these negative aspects can create a long-term series of nutritional and psycho-emotional imbalances. Our results evidence that complex surveys among the population are regularly required to investigate nutritional or lifestyle deficiencies; moreover, it could be helpful in further educational measures in nutrition, food, and environmental safety.

Bee Bread: A Promising Source of Bioactive Compounds with Antioxidant Properties-First Report on Some Antimicrobial Features.

Bee bread has received attention due to its high nutritional value, especially its phenolic composition, which enhances life quality. The present study aimed to evaluate the chemical and antimicrobial properties of bee bread (BB) samples from Romania. Initially, the bee bread alcoholic extracts (BBEs) were obtained from BB collected and prepared by Apis mellifera carpatica bees. The chemical composition of the BBE was characterized by Fourier Transform Infrared Spectroscopy (FTIR) and the total phenols and flavonoid contents were determined. Also, a UHPLC-DAD-ESI/MS analysis of phenolic compounds (PCs) and antioxidant activity were evaluated. Furthermore, the antimicrobial activity of BBEs was evaluated by qualitative and quantitative assessments. The BBs studied in this paper are provided from 31 families of plant species, with the total phenols content and total flavonoid content varying between 7.10 and 18.30 mg gallic acid equivalents/g BB and between 0.45 and 1.86 mg quercetin equivalents/g BB, respectively. Chromatographic analysis revealed these samples had a significant content of phenolic compounds, with flavonoids in much higher quantities than phenolic acids. All the BBEs presented antimicrobial activity against all clinical and standard pathogenic strains tested. Salmonella typhi, Candida glabrata, Candida albicans, and Candida kefyr strains were the most sensitive, while BBEs' antifungal activity on C. krusei and C. kefyr was not investigated in any prior research. In addition, this study reports the BBEs' inhibitory activity on microbial (bacterial and fungi) adhesion capacity to the inert substratum for the first time.

Pharmacotechnical, Physico-Chemical, and Antioxidant Evaluation of Newly Developed Capsule Formulations.

The excess of free radicals causes numerous imbalances in the body that lead to premature aging, the degradation of internal structures, and the appearance of numerous pathologies responsible for the increased risk of premature death. The present work aims to evaluate the physical, chemical, pharmacotechnical, and antioxidant activity of newly achieved capsule formulations. These two formulations were F1a.i., which contains melatonin:biotin:coenzyme Q10 (weight ratio of 1:2:60), and F2a.i., which contains quercetin:resveratrol:biotin:coenzyme Q10 (weight ratio of 10:10:1:10). The adequate selection of the excipient types and amounts for final capsule formulations (F1c.c., F2c.c.) was based on preformulation studies performed on the powders containing active ingredients. The antioxidant activity assessed using three methods (ABTS, DPPH, and FRAP) compared with acid ascorbic as a positive control demonstrated that the F2c.c. formulation possesses the strongest antioxidant capacity. The results confirmed the suitable formulation and the accurate selection of the types and amounts of active ingredients, as well as the auxiliary excipients used in newly developed capsule formulations as supplements with an excellent antioxidant effect on the human body.

Resistance, Tolerance, Virulence and Bacterial Pathogen Fitness-Current State and Envisioned Solutions for the Near Future.

The current antibiotic crisis and the global phenomena of bacterial resistance, inherited and non-inherited, and tolerance-associated with biofilm formation-are prompting dire predictions of a post-antibiotic era in the near future. These predictions refer to increases in morbidity and mortality rates as a consequence of infections with multidrug-resistant or pandrug-resistant microbial strains. In this context, we aimed to highlight the current status of the antibiotic resistance phenomenon and the significance of bacterial virulence properties/fitness for human health and to review the main strategies alternative or complementary to antibiotic therapy, some of them being already clinically applied or in clinical trials, others only foreseen and in the research phase.

Chemical and Biological Studies of Achillea setacea Herba Essential Oil-First Report on Some Antimicrobial and Antipathogenic Features.

The essential oil of Achillea setacea was isolated by hydrodistillation and characterized by GC-MS. The antioxidant and antimicrobial activity of Achillea setacea essential oil was evaluated, as well as its biocompatibility (LDH and MTT methods). DPPH, FRAP, and CUPRAC methods were applied for antioxidant activity evaluation, while qualitative and quantitative assays (inhibition zone diameter, minimum inhibitory concentration, and minimum fungicidal concentration), NO release (by nitrite concentration determination), and microbial adhesion capacity to the inert substrate (the biofilm microtiter method) were used to investigate the antimicrobial potential. A total of 52 compounds were identified by GC-MS in A. setacea essential oil, representing 97.43% of the total area. The major constituents were borneol (32.97%), 1,8-cineole (14.94%), camphor (10.13%), artemisia ketone (4.70%), α-terpineol (3.23%), and γ-eudesmol (3.23%). With MICs ranging from 0.78 to 30 µg/mL, the A. setacea essential oil proved to inhibit the microbial adhesion and induce the NO release. To the best of our knowledge, the present study reports for the first time the antimicrobial activity of A. setacea EO against clinically and biotechnologically important microbial strains, such as Shigella flexneri, Listeria ivanovii, L. innocua, Saccharomyces cerevisiae, Candida glabrata, Aspergillus niger, Rhizopus nigricans, Cladosporium cladosporioides, and Alternaria alternata, demonstrating its antimicrobial applications beyond the clinical field.

Wound Healing and Anti-Inflammatory Effects of a Newly Developed Ointment Containing Jujube Leaves Extract.

Ziziphus jujuba Mill. (jujube) is a well-known medicinal plant with pronounced wound healing properties. The present study aimed to establish the chemical composition of the lyophilized ethanolic extract from Romanian Ziziphus jujuba leaves and to evaluate the healing and anti-inflammatory properties of a newly developed lipophilic ointment containing 10% dried jujube leaves extract. The ultra-High-Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry method was used, and 47 compounds were detected, among them the novel epicatechin and caffeic acid. The extract contains significant amounts of rutin (29.836 mg/g), quercetin (15.180 mg/g) and chlorogenic acid (350.96 µg/g). The lipophilic ointment has a slightly tolerable pH, between 5.41-5.42, and proved to be non-toxic in acute dermal irritation tests on New Zealand albino rabbits and after repeated administration on Wistar rats. The ointment also has a healing activity comparable to Cicatrizin (a pharmaceutical marketed product) on Wistar rats and a moderate anti-inflammatory action compared to the control group, but statistically insignificant compared to indomethacin in the rat-induced inflammation test by intraplantar administration of kaolin. The healing and anti-inflammatory properties of the tested ointment are due to phenolic acids and flavonoids content, less because of minor components as apocynin, scopoletin, and isofraxidin.

Therapeutic Benefits and Dietary Restrictions of Fiber Intake: A State of the Art Review.

Throughout history, malnutrition and deficiency diseases have been a problem for our planet's population. A balanced diet significantly influences everyone's health, and fiber intake appears to play a more important role than previously thought. The natural dietary fibers are a category of carbohydrates in the constitution of plants that are not completely digested in the human intestine. High-fiber foods, such as fruits, vegetables and whole grains, have consistently been highly beneficial to health and effectively reduced the risk of disease. Although the mode of action of dietary fiber in the consumer body is not fully understood, nutritionists and health professionals unanimously recognize the therapeutic benefits. This paper presents the fiber consumption in different countries, the metabolism of fiber and the range of health benefits associated with fiber intake. In addition, the influence of fiber intake on the intestinal microbiome, metabolic diseases (obesity and diabetes), neurological aspects, cardiovascular diseases, autoimmune diseases and cancer prevention are discussed. Finally, dietary restrictions and excess fiber are addressed, which can cause episodes of diarrhea and dehydration and increase the likelihood of bloating and flatulence or even bowel obstruction. However, extensive studies are needed regarding the composition and required amount of fiber in relation to the metabolism of saprotrophic microorganisms from the enteral level and the benefits of the various pathologies with which they can be correlated.

Bee Pollen Extracts: Chemical Composition, Antioxidant Properties, and Effect on the Growth of Selected Probiotic and Pathogenic Bacteria.

This paper evaluated the chemical and biological properties of bee pollen samples from Romania. Firstly, the bee pollen alcoholic extracts (BPEs) were obtained from raw bee pollen harvested by Apis mellifera carpatica bees. The chemical composition of BPE was obtained by determination of total phenol content and total flavonoid content, UHPLC-DAD-ESI/MS analysis of phenolic compounds, and GC-MS analysis of fatty acids, esters, and terpenes. Additionally, the antioxidant activity was evaluated by the Trolox Equivalent Antioxidant Capacity method. Furthermore, the biological properties of BPE were evaluated (antimicrobial and cytotoxic activity). The raw BP samples studied in this paper had significant phenolic acid and flavonoid content, and moderate fatty acid, ester, and terpene content. P1, P2, and P4 have the highest TPC and TFC levels, and the best antioxidant activity. All BPEs studied had antimicrobial activity on pathogenic strains isolated from the clinic or standard strains. A synergistic antimicrobial effect of the BPEs was observed along with the soluble compounds of L. rhamnosus MF9 and E. faecalis 2M17 against some pathogenic (clinical) strains and, considering the tumour proliferation inhibitory activity, makes BP a potential prebiotic and antitumour agent for the gut environment.

Food Habits and Lifestyle of Romanians in the Context of the COVID-19 Pandemic.

The pandemic caused by the SARS-CoV-2 virus has produced significant changes in socio-cultural life, diet, and interpersonal relationships across the world's population. The present study aims to identify changes in lifestyle and diet among the Romanian population one year after the onset of the COVID-19 pandemic. An online questionnaire with 58 items (addressing the following aspects: socio-demographic and anthropometric data, current eating habits, and lifestyle changes) was distributed using institutional mailing lists and social media. A total number of 2040 respondents participated in the study, of whom 1464 were women, and 576 men. Among the respondents, 1598 came from urban areas and 442 from rural areas. The processing of the collected data showed significant changes in the behavior of the respondents caused by the pandemic situation with psycho-affective changes in some cases. The number of people who had anxiety, depression and nervousness increased by up to 20%. The majority of respondents (over 57%) were up to 30 years old, either students (43.50%) or employees going to workplaces (33.20%). Analyzing eating habits, we found that diet modification was needed to increase the daily consumption of fruits, vegetables, fish, and seafood. Regarding weight status during the pandemic, we noticed that 34.7% of normal-weight respondents said that they gained weight while 49.7% of overweight people and 52.5% of obese people said that they gained weight (p < 0.0001). Regarding psycho-emotional behavior, 11.81% of the surveyed women stated that they frequently had depressive states during the pandemic period and 11.63% of the men stated that they frequently presented depressive states during the pandemic (p = 0.005).

Black Sea Mussels Qualitative and Quantitative Chemical Analysis: Nutritional Benefits and Possible Risks through Consumption.

Mussels have a particular nutritional value, representing a highly valued food source and thus sought after worldwide. Their meat is a real culinary delicacy, rich in proteins, lipids, carbohydrates, trace elements, enzymes, and vitamins. The seasonal variation of mussels' biochemical composition has been studied to determine the best harvesting period to capitalize on various biologically active fractions. In this work biochemical determinations have been performed on fresh flesh samples of Mytilus galloprovincialis specimens from the Black Sea coast to study seasonal variations in mussels' biochemical compounds. An analysis of significant lipid classes and the fatty acid composition of lipid extracts obtained from mussel flesh has also been performed. Since mussels retain pollutants from the marine environment, in parallel, the concentration of heavy metals in the meat of mussels collected for the analysis of the chemical composition was investigated. The impact and risk of heavy metal poisoning due to food consumption of mussels contaminated due to pollution of the marine harvesting area was evaluated by the bio-concentration factor of metals and estimated daily intakes of heavy metals through mussel consumption.

Original Contributions to the Chemical Composition, Microbicidal, Virulence-Arresting and Antibiotic-Enhancing Activity of Essential Oils from Four Coniferous Species.

This study aimed to establish the essential oil (EO) composition from young shoots of Picea abies, Larix decidua, Pseudotsuga menziesii, and Pinus nigra harvested from Romania and evaluate their antimicrobial and anti-virulence activity, as well as potential synergies with currently used antibiotics. The samples' EO average content varied between 0.62% and 1.02% (mL/100 g plant). The mono- and sesquiterpene hydrocarbons were dominant in the composition of the studied EOs. The antimicrobial activity revealed that the minimum inhibitory concentration (MIC) values for the tested EOs and some pure compounds known for their antimicrobial activity ranged from 6.25 to 100 µL/mL. The most intensive antimicrobial effect was obtained for the Pinus nigra EO, which exhibited the best synergistic effect with some antibiotics against Staphylococcus aureus strains (i.e., oxacillin, tetracycline, erythromycin and gentamycin). The subinhibitory concentrations (sMIC) of the coniferous EOs inhibited the expression of soluble virulence factors (DN-ase, lipase, lecithinase, hemolysins, caseinase and siderophore-like), their efficiency being similar to that of the tested pure compounds, and inhibited the rhl gene expression in Pseudomonas aeruginosa, suggesting their virulence-arresting drug potential.

Chemical Composition, Antipathogenic and Cytotoxic Activity of the Essential Oil Extracted from Amorpha fruticosa Fruits.

The purpose of this paper was to characterize and investigate the antimicrobial potential of Amorpha fruticosa fruits essential oil (EO). The EO was extracted by hydrodistillation, analyzed by GC-MS, and then evaluated for its interaction with microbial and mammalian cells. The antimicrobial activity was assessed against bacterial and fungal strains, in a planktonic and adherent growth state, using qualitative and quantitative assays. The main components identified in A. fruticosa fruits EO were δ-cadinene, γ-muurolene, and α-muurolene. The Gram-positive strains proved to be more susceptible than Gram-negative bacteria and fungal strains. The EO exhibited good antibiofilm activity, inhibiting the microbial adherence to the inert (96-well plates and Foley catheter section) and cellular substrata. The flow cytometry analysis revealed as one of the possible mechanisms of antimicrobial action the alteration of cell membrane hydrophobicity. The cytotoxicity on the L929 cell line occurred at concentrations higher than 0.3 mg/mL. Taken together, our results demonstrate that A. fruticosa fruits EO contains active compounds with selective inhibitory effect on different microbial strains in planktonic and biofilm growth state, explained at least partially by the interference with microbial membranes due to their hydrophobic character.

Valorization of Gleditsia triacanthos Invasive Plant Cellulose Microfibers and Phenolic Compounds for Obtaining Multi-Functional Wound Dressings with Antimicrobial and Antioxidant Properties.

Gleditsia triacanthos is an aggressive invasive species in Eastern Europe, producing a significant number of pods that could represent an inexhaustible resource of raw material for various applications. The aim of this study was to extract cellulose from the Gleditsia triacanthos pods, characterize it by spectrophotometric and UHPLC-DAD-ESI/MS analysis, and use it to fabricate a wound dressing that is multi-functionalized with phenolic compounds extracted from the leaves of the same species. The obtained cellulose microfibers (CM) were functionalized, lyophilized, and characterized by ATR-FTIR and SEM. The water absorption and retention capacity as well as the controlled release of phenolic compounds with antioxidant properties evaluated in temporal dynamics were also determined. The antimicrobial activity against reference and clinical multi-drug-resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, Enterobacter cloacae, Candida albicans, and Candida parapsilosis strains occurred immediately after the contact with the tested materials and was maintained for 24 h for all tested microbial strains. In conclusion, the multi-functionalized cellulose microfibers (MFCM) obtained from the reproductive organs of an invasive species can represent a promising alternative for the development of functional wound dressings with antioxidant and antimicrobial activity, as well as being a scalable example for designing cost-effective, circular bio-economy approaches to combat the accelerated spread of invasive species.

Heavy metal and pesticide levels in dairy products: Evaluation of human health risk.

Cattle milk's health benefits can be compromised by the presence of contaminants. The levels of cadmium, copper, lead and zinc, and residues of dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD), dichlorodiphenyltrichloroethane (DDT) were determined in soil, milk and cheese samples collected from cow farms from 3 Romanian areas with industrial and agriculture tradition. A new methodology was applied for the determination of the corrected estimated daily intake (cEDI) corresponding to the aggregate dietary exposure. For the risk assessment, we calculated the source hazard quotient (HQs) for each contaminant and the adversity specific hazard index (HIA). Cadmium, copper, lead and zinc, and the sum of DDT levels in soil samples were below maximum residue levels (MRLs). The MRLs of lead and DDD were exceeded in milk and cheese samples from all the 3 areas. The MRLs of copper and zinc were exceeded in cheese samples from area 2 and 3. HQs >10 for lead indicates increased risk, while HQ > 1 for copper and sum of DDT indicates moderate risk for both milk and cheese. By calculating the HIA, we identified a moderate and increase risk for nephrotoxicity, hepatotoxicity, hematotoxicity, cardiotoxicity and reproduction toxicity after consumption of the dairy products from the 3 areas.

Saccharomyces cerevisiae cells lacking transcription factors Skn7 or Yap1 exhibit different susceptibility to cyanidin.

Anthocyanidins - the aglycone moiety of anthocyanins - are responsible for the antioxidant traits and for many of the health benefits brought by the consumption of anthocyanin-rich foods, but whether excessive anthocyanidins are deleterious to living organisms is still a matter of debate. In the present study we used the model eukaryotic microorganism Saccharomyces cerevisiae to evaluate the potential toxicity of cyanidin, one of the most prevalent anthocyanidins found in berries, grapes, purple vegetables, and red wine. We found that yeast cells lacking the transcription factors responsible for regulating the response to oxidative stress - Skn7 and Yap1 - exhibited different sensitivities to cyanidin. Cells lacking the transcription factor Skn7 were sensitive to low concentrations of cyanidin, a trait that was augmented by exposure to visible light, notably blue or green light. In contrast, the growth of yeast cells devoid of Yap1 was stimulated by low concentrations, but it was impaired by high cyanidin exposure. High, but not low cyanidin was shown to induce Yap1 translocation from cytosol to nucleus, probably by generating reactive oxygen species such as H2O2. Taken together, these observation suggested that Skn7 and Yap1 have complementary roles in adaptation to cyanidin stress, with Skn7 involved in adaptation to low concentrations and with Yap1 responsible for adaptation to high concentrations of cyanidin. The results imply that caution is needed when utilizing cyanidin-enriched supplements, especially when in combination with prolonged exposure to visible light.

In Vitro Evaluation of the Antimicrobial and Immunomodulatory Activity of Culinary Herb Essential Oils as Potential Perioceutics.

Due to their antimicrobial, immunomodulatory, antioxidant, and regenerative activities, culinary herbs have multiple medicinal uses, among which to prevent and treat oral diseases. The whole essential oils (EOs) have multiple advantages over purified components, such as a low probability to select for antimicrobial resistance, synergic effects of different components, and multi-pharmacological activities. In this study, we aimed to evaluate essential oils from Salvia officinalis (sage), Satureja hortensis (summer savory), and Anethum graveolens (dill) using an in vitro analysis of their antimicrobial activity against Gram-positive and Gram-negative bacterial strains isolated from the oral cavity of patients with periodontitis; the assays addressed both the planktonic and biofilm growth states and used culture-based approaches. Some of the tested EOs exhibited excellent bactericidal and antibiofilm activity, being active at concentrations as low as 0.08-1.36 mg/mL. Flow cytometry was used to investigate the potential mechanisms of their antibacterial activity and confirmed that the tested EOs act by permeabilizing the bacterial membrane and by inhibiting the activity of the efflux pumps. The immunomodulatory effect of the three EOs was determined by analyzing the gene expression profiles for pro- and anti-inflammatory cytokines of the THP-1 cells. The summer savory EO induced a clear proinflammatory effect, while the others did not significantly influence the cytokines profile of the tested cells. Taken together, our results indicate that summer savory EO and, to a lesser extent, sage and dill EOs could be used to inhibit bacteria involved in oral plaque formation and to reduce the expression of genes known to contribute to the inflammatory response using cell culture assessment.

Dietary Anthocyanins and Stroke: A Review of Pharmacokinetic and Pharmacodynamic Studies.

Cerebrovascular accidents are currently the second major cause of death and the third leading cause of disability in the world, according to the World Health Organization (WHO), which has provided protocols for stroke prevention. Although there is a multitude of studies on the health benefits associated with anthocyanin (ACN) consumption, there is no a rigorous systematization of the data linking dietary ACN with stroke prevention. This review is intended to present data from epidemiological, in vitro, in vivo, and clinical studies dealing with the stroke related to ACN-rich diets or ACN supplements, along with possible mechanisms of action revealed by pharmacokinetic studies, including ACN passage through the blood-brain barrier (BBB).