Interactions between grapefruit juice and psychotropic medications: an update of the literature and an original case series.

INTRODUCTION: There is a large body of preclinical data implicating that grapefruit juice (GJ) inhibits many CYP 450 isoforms. The potential of GJ-to-drug is of high relevance to clinical psychiatry, because a wide range of psychotropic medicines undergo CYP 450 metabolism and P-gp transport. AREAS COVERED: Relevant data were identified by searching the electronic databases up to February 2024. This work constitutes a summary of preclinical and clinical data on GJ impact on CYP 450 metabolism, P-glycoprotein, and organic anion-transporting polypeptides (OATPs), with focus on studies that assessed GJ-to-psychotropic drug interactions. Additionally, an unpublished case series of nine patients is provided. EXPERT OPINION: The impact of GJ on CYP 3A4 appears to be the critical mechanism for the majority of GJ-to-psychopharmacotherapy interactions described in human studies or case reports. However, there are studies and cases of patients clearly showing that this is not the only route explaining the GJ effect, and at times, this particular is of no relevance and that other CYP 450 isoforms as well as drug transporting proteins might be involved. The risk of GJ-to-psychotropic drugs needs to be further evaluated in a 'real-world' setting and apply not only measures of pharmacokinetics but also treatment effectiveness and safety.

Amination of naringinase to improve citrus juice debittering using a catalyst immobilized on glyoxyl-agarose.

A naringinase complex was chemically aminated prior to its immobilization on glyoxyl-agarose to develop a robust biocatalyst for juice debittering. The effects of amination on the optimal pH and temperature, thermal stability, and debittering performance were analyzed. Concentration of amino groups on catalysts surface increased in 36 %. Amination reduced the ß-glucosidase activity of naringinase complex; however, did not affect optimal pH and temperature of the enzyme and it favored immobilization, obtaining α-l-rhamnosidase and ß-d-glucosidase activities of 1.7 and 4.2 times the values obtained when the unmodified enzymes were immobilized. Amination favored the stability of the immobilized biocatalyst, retaining 100 % of both activities after 190 h at 30 °C and pH 3, while its non-aminated counterpart retained 80 and 52 % of α-rhamnosidase and ß-glucosidase activities, respectively. The immobilized catalyst showed a better performance in grapefruit juice debittering, obtaining a naringin conversion of 7 times the value obtained with the non-aminated catalyst.

Cellulose nanofiber-based multifunctional composite films integrated with zinc doped-grapefruit peel-based carbon quantum dots.

This study aimed to develop a multifunctional active composite film to extend the shelf life of minced pork. The composite film was prepared by incorporating zinc-doped grapefruit peel-derived carbon quantum dots (Zn-GFP-CD) into a cellulose nanofiber (CNF) matrix. The resulting film significantly improved UV-blocking properties from 39.0 % to 85.7 % while maintaining the film transparency. Additionally, the CNF/Zn-GFP-CD5% composite film exhibits strong antioxidant activity with ABTS and DPPH radical scavenging activities of 99.8 % and 77.4 %, respectively. The composite film also showed excellent antibacterial activity against both Gram-negative and Gram-positive bacteria. When used in minced pork packaging, the composite films effectively inhibit bacterial growth, maintaining bacterial levels below 7 Log CFU/g after 15 days and sustaining a red color over a 21-day storage period. Additionally, a significant reduction in the lipid oxidation of the minced pork was observed. These CNF/Zn-GFP-CD composite films have a great potential for active food packaging applications to extend shelf life and maintain the visual quality of packaged meat.

Anti-breast cancer activity of the essential oil from grapefruit mint (Mentha suaveolens × piperita).

Grapefruit mint (Mentha suaveolens × piperita) is a hybrid, perennial, and aromatic plant widely cultivated all over the world and used in the food, cosmetics, and pharmaceutical industries mostly for its valuable essential oil. Herein, we evaluated the anticancer activity of the grapefruit mint essential oil, cultivated in Iran. For the chemical composition analysis of essential oil, GC-MS was used. MTT assay was utilized for assessing the cytotoxic activity of the essential oil. The type of cell death was determined by annexin V/PI staining. Essential oil effect on the expression of maternally expressed gene 3 (MEG3), a regulatory lncRNA involved in cell growth, proliferation, and metastasis, was studied using qRT-PCR. Linalool (43.9%) and linalool acetate (40.1%) were identified as the dominant compounds of essential oil. Compared with MCF-7, the MDA-MB-231 cells were more sensitive to essential oil (IC50 = 7.6 µg/ml in MCF-7 and 5.9 µg/ml in MDA-MB-231 after 48 h). Essential oil induced cell death by apoptosis. Wound healing scratch assay confirmed the anti-invasive effect of essential oil. In addition, essential oil upregulated the tumor suppressor MEG3 in breast cancer cells. These results provide new insights into grapefruit mint essential oil potential application as an anticancer adjuvant in combination treatments for breast cancer patients.

Environmentally Friendly Approach to Pectin Extraction from Grapefruit Peel: Microwave-Assisted High-Pressure CO2/H2O.

In this research, pectin extraction from grapefruit peel (GPP) was performed using a microwave-assisted high-pressure CO2/H2O (MW-HPCO2) system. The Box-Behnken design of response surface methodology was applied for the optimization of MW-HPCO2 extraction conditions to obtain the highest pectin yield. The effects of temperature, time, and liquid/solid ratio on pectin yield were examined in the range of 100-150 °C, 5-15 min, and 10-20 mL g-1, respectively. Under the optimum extraction conditions (147 °C, 3 min, and 10 mL g-1), pectin was obtained with a yield of 27.53%. The results obtained showed that the extraction temperature and time had a strong effect on the pectin yield, while the effect of the liquid/solid ratio was not significant, and the pectin was effectively extracted from grapefruit peel (GP) using MW-HPCO2. Additionally, the application of GPP in apricot jam showed that MW-HPCO2-GPP can be used as a thickener in the food industry. The yield and physicochemical properties (ash, protein, galacturonic acid, reducing sugar and methoxyl content, degree of esterification, equivalent weight, color, viscosity) of pectin extracted in the optimum conditions of the MW-HPCO2 method were superior to pectin extracted by the traditional method. The results of this study revealed that MW-HPCO2 could be an innovative green and rapid technique for pectin extraction.

Structural, mechanical, barrier and antioxidant properties of pectin and xanthan gum edible films loaded with grapefruit essential oil.

This research focused on the development of films based on pectin and xanthan gum composite loaded with different concentrations of grapefruit essential oil (GFO). The fabricated films were characterized to assess the effect of GFO on the structural, mechanical, barrier, chemical, and antioxidant properties. The addition of GFO enhanced the functional properties of the films, as confirmed by FTIR analysis showing molecular interactions within the film matrix. SEM observations revealed that films with higher GFO content had a smoother, more compact structure with uniform oil distribution. Films loaded with oil demonstrated enhanced water resistance, as their decreased permeability ranged from 0.733 ± 0.009 to 0.561 ± 0.020 (g mm)/(m2.h.kPa). Additionally, these films showed a notable increase in tensile strength, ranging from 2.91 ± 0.19 to 8.55 ± 0.62 MPa. However, the addition of oil led to a reduction in the elongation at break of the films, which decreased from 52.84 ± 3.41 % to 12.68 ± 1.52 %, and a decline in transparency from 87.57 ± 0.65 % to 76.18 ± 1.12 %. Fabricated films exhibited enhanced antioxidant properties, as evidenced by increased DPPH• and ABTS•+ radical scavenging activities with the addition of GFO. The findings of the current study suggest that GFO is an effective natural additive for enhancing the physiochemical properties of pectin and xanthan gum-based films, making them more suitable for food packaging applications.

Integration of covalent organic frameworks and molecularly imprinted polymers for selective extraction of flavonoid naringenin from grapefruit (Citrus × paradisi Macf.) peels.

Grapefruit (Citrus × paradisi Macf.) peel, a by-product of the citrus-processing industry, possesses an important economic value due to the richness of bioactive compounds. In this study, boron-linked covalent organic frameworks integrated with molecularly imprinted polymers (CMIPs) were developed via a facile one-pot bulk polymerization approach for the selective extraction of naringenin from grapefruit peel extract. The obtained CMIPs possessed a three-dimensional network structure with uniform pore size distribution, large surface areas (476 m2/g), and high crystallinity. Benefiting from the hybrid functional monomer APTES-MAA, the acylamino group can coordinate with the boronate ligands of the boroxine-based framework to form B-N bands, facilitating the integration of imprinted cavities with the aromatic skeleton. The composite materials exhibited a high adsorption capacity of 153.65 mg/g, and a short adsorption equilibrium time of 30 min for naringenin, together with favorable selectivity towards other flavonoid analogues. Additionally, the CMIPs captured the template molecules through π-π* interaction and hydrogen bonding, as verified by FT-IR and XPS. Furthermore, they had good performance when employed to enrich naringenin in grapefruit peels extract compared with the common adsorbent materials including AB-8, D101, cationic exchange resin, and active carbon. This research highlights the potential of CMIPs composite materials as a promising alternative adsorbent for naringenin extraction from grapefruit peel.

Alginate Microbeads Containing Halloysite and Layered Double Hydroxide as Efficient Carriers of Natural Antimicrobials.

The present paper describes the preparation and characterization of novel microbeads from alginate filled with nanoclay such as halloysite nanotubes (HNTs). HNTs were used as support for the growth of layered double hydroxide (LDH) crystals producing a flower-like structure (HNT@LDH). Such nanofiller was loaded with grapefruit seed oil (GO), an active compound with antimicrobial activity, up to 50% wt. For comparison, the beads were also loaded with HNT and LDH separately, and filled with the same amount of GO. The characterization of the filler was performed using XRD and ATR spectroscopy. The beads were analyzed through XRD, TGA, ATR and SEM. The functional properties of the beads, as nanocarriers of the active compound, were investigated using UV-vis spectroscopy. The release kinetics were recorded and modelled as a function of the structural characteristics of the nanofiller.

Identification and structural characterization of key prebiotic fraction of soluble dietary fiber from grapefruit peel sponge layer and its regulation effect on gut microbiota.

In this study, the key prebiotic fraction of grapefruit peel sponge layer soluble dietary fiber (GSLSDF) was identified, and its structure characteristics and modulatory effect on intestinal microorganisms were investigated. Firstly, two fractions (GSLSDF-1 and GSLSDF-2) were isolated from GSLSDF, and the GSLSDF-1 showed a better prebiotic activity. Subsequently, GSLSDF-1 was found to have a low molecular weight and crystallinity, a loose and porous microstructure, and a high glucose content. Meanwhile, GSLSDF-1 was a dextran with a main chain linked by ß-1, 4 glycosidic bonds and branched by a ß-1, 6 glycosidic bonds. These structural characteristics were responsible for the favorable prebiotic activity of GSLSDF-1. Finally, the regulation effect of GSLSDF-1 on gut microbiota was analyzed in vitro fecal fermentation. Compared with the blank and GSLSDF groups, GSLSDF-1 could increase the relative abundances of Lactobacillus, Bacteroides, Bifidobacterium and Faecalibacterium coupled with decrease the relative abundances of Clostridium and Clostridioides. Furthermore, GSLSDF-1 promoted the production of short-chain fatty acids (SCFAs) by modulating the SCFAs synthesis pathway of intestinal microorganisms, while the NH3-N synthesis of intestinal microorganisms was inhibited by GSLSDF-1. Above results indicated that GSLSDF-1 was the key prebiotic fraction of GSLSDF, which could effectively optimize the intestinal microorganism composition.

Ex Vivo Anti-Leukemic Effect of Exosome-like Grapefruit-Derived Nanovesicles from Organic Farming-The Potential Role of Ascorbic Acid.

Citrus fruits are a natural source of ascorbic acid, and exosome-like nanovesicles obtained from these fruits contain measurable levels of ascorbic acid. We tested the ability of grapefruit-derived extracellular vesicles (EVs) to inhibit the growth of human leukemic cells and leukemic patient-derived bone marrow blasts. Transmission electron microscopy and nanoparticle tracking analysis (NTA) showed that the obtained EVs were homogeneous exosomes, defined as exosome-like plant-derived nanovesicles (ELPDNVs). The analysis of their content has shown measurable amounts of several molecules with potent antioxidant activity. ELPDNVs showed a time-dependent antiproliferative effect in both U937 and K562 leukemic cell lines, comparable with the effect of high-dosage ascorbic acid (2 mM). This result was confirmed by a clear decrease in the number of AML blasts induced by ELPDNVs, which did not affect the number of normal cells. ELPDNVs increased the ROS levels in both AML blast cells and U937 without affecting ROS storage in normal cells, and this effect was comparable to ascorbic acid (2 mM). With our study, we propose ELPDNVs from grapefruits as a combination/supporting therapy for human leukemias with the aim to improve the effectiveness of the current therapies.

Composite optimization and characterization of dietary fiber-based edible packaging film reinforced by nanocellulose from grapefruit peel pomace.

The development of edible packaging films was motivated due to resource waste and environmental damage caused by chemically produced plastic packaging. The development of edible packaging film based on grapefruit peel pomace dietary fiber has significant technological and functional potential because grapefruit processing waste is a potential source of high-quality dietary fiber. In this study, the first successful development of an edible packaging film based on dietary fiber using grapefruit soluble dietary fiber (GSDF) from grapefruit peel pomace as a substrate and nanocellulose (GNCC) as a filler was developed. Principal component analysis, membership function synthesis, and response surface methods were used to determine the optimal process to prepare the edible packaging films, and the impact of GNCC on this material was analyzed. The results showed that the overall performance score of the edible packaging film with 1 wt% GNCC was 0.764. The maximum pyrolysis temperature increased from 226.36 °C to 227.10 °C, the melting temperature (Tm) increased by 5.54 °C, the crystallinity increased by 2.95 %. The film solution exhibited non-Newtonian characteristics and a solid-like property. Our results showed that the edible packaging film developed from grapefruit peel pomace and dietary fiber could have several potential applications in the food packaging field.

An eco-friendly ultra-performance liquid chromatography-mass spectrometry method for quantification of rivaroxaban and ticagrelor in rat plasma: grapefruit interactions.

Aim: An eco-friendly ultra-performance liquid chromatography-tandem mass spectrometry method was developed to study the pharmacokinetics of rivaroxaban and ticagrelor in rat plasma, utilizing moxifloxacin as an internal standard. The food-drug interaction between grapefruit juice and these drugs was also investigated. Methods: Liquid-liquid extraction was used. A nonporous stationary phase Agilent® Poroshell 120EC C18 column was used with methanol: 0.1% aqueous formic acid (95:5 v/v) as a mobile phase. The detection was performed in multiple reaction monitoring mode using positive electrospray ionization. The method's validation was conducted in accordance with US FDA and European Medicines Agency guidelines. Results & conclusion: Grapefruit juice should be ingested with caution in patients treated with antithrombotic medications as it may increase their plasma concentration, inducing bleeding, and requires close clinical monitoring.

Antibacterial Activity of Zinc Oxide Nanoparticles Loaded with Essential Oils.

One major problem with the overuse of antibiotics is that the microorganisms acquire resistance; thus the dose must be increased unsustainably. To overcome this problem, researchers from around the world are actively investigating new types of antimicrobials. Zinc oxide (ZnO) nanoparticles (NPs) have been proven to exhibit strong antimicrobial effects; moreover, the Food and Drugs Administration (FDA) considers ZnO as GRAS (generally recognized as safe). Many essential oils have antimicrobial activity and their components do not generate resistance over time. One of the drawbacks is the high volatility of some components, which diminishes the antimicrobial action as they are eliminated. The combination of ZnO NPs and essential oils can synergistically produce a stronger antimicrobial effect, and some of the volatile compounds can be retained on the nanoparticles' surface, ensuring a better-lasting antimicrobial effect. The samples were characterized with X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), and thermal analysis (TG-DSC) coupled with analysis of evolved gases using FTIR. The ZnO NPs, with a size of ~35 nm, exhibited a loading between 1.44% and 15.62%-the lower values were specific for limonene-containing oils (e.g., orange, grapefruit, bergamot, or limette), while high values were obtained from cinnamon, minzol, thyme, citronella, and lavender oils-highlighting differences among non-polar terpenes and alcohol or aldehyde derivatives. The antibacterial assay indicated the existence of a synergic action among components and a high dependency on the percentage of loaded oil. Loaded nanoparticles offer immense potential for the development of materials with specific applications, such as wound dressings or food packaging. These nanoparticles can be utilized in scenarios where burst delivery is desired or when prolonged antibacterial activity is sought.

Randomized Controlled Study in the Use of Aromatherapy for Pain Reduction and to Reduce Opioid Use in the Emergency Department.

INTRODUCTION: This study aimed to evaluate the effects of aromatherapy on emergency department patients' perception of pain and its ability to reduce the use of opioids in an emergency department. METHODS: This randomized, controlled, single-blinded study was conducted in a suburban/rural freestanding emergency department with a therapeutic group, sham group, and control group. RESULTS: A total of 230 patients, 171 females and 59 males, completed the study. Of those who received the therapeutic agent, an average reduction in pain of 1.04 points on the pain scale was reported, whereas the sham group averaged 0.38 and the control group 0.23. There was a statistically significant reduction of pain scores in the therapeutic group. A total of 13 received opioid pain medication during their visit. Of these, the therapeutic group averaged a total of 2.67 morphine milligram equivalents for their visit compared with 3.63 in the sham group and 4.36 in the control group; however, statistical significance was not achieved. DISCUSSION: This study supported what other studies have found, indicating that aromatherapy is effective in reducing pain. A difference between the placebo effect and a true therapeutic effect was seen by using a control group apart from the sham and therapeutic groups. Despite the small effect size (0.3), implementation of aromatherapy into standard practice may be practical considering the anxiolytic effects that have been shown in other studies. Aromatherapy with essential oils should be considered as another tool to use in a multimodal approach in the treatment of pain in the emergency department setting.

Propylene Glycol Potentiates the Inhibitory Action of CTZ Paste on Antibiotic-Resistant Enterococcus faecalis Isolated from the Root Canal: An In Vitro Study.

This study aimed to evaluate if the change of vehicle for CTZ (Chloramphenicol, Tetracycline, zinc oxide, and Eugenol) paste improves the inhibition of Enterococcus faecalis in vitro. The vehicles evaluated alone and mixed with CTZ were Eugenol, propylene glycol (PG), super-oxidized solution (SOS), grapefruit-seed extract (GSE), and 0.9% saline solution as a negative control. A clinical isolate of E. faecalis was morphologically and biochemically characterized, and its antimicrobial susceptibility was tested using 20 antimicrobial agents. Once characterized, the clinical isolate was cultivated to perform the Kirby-Bauer disc diffusion method with paper discs embedded with the different vehicles mixed or used alone, and incubated at 37 °C for 24 h. Data were analyzed using one-way ANOVA, and the means were compared using Tukey test with a significance level of p < 0.05. For vehicles used alone, GSE presented the greatest inhibition showing a statistically significant difference with the rest of the vehicles. When vehicles were mixed with the CTZ paste, PG showed a greater inhibition with a statistically significant difference from the rest of the vehicles. In conclusion, the vehicle used to mix the CTZ paste plays an important role in the inhibition of E. faecalis in vitro; therefore, we consider that this can be an important factor to achieve success in the use of this technique.

Examining the Naringin Content and Sensory Characteristics of Functional Chocolate Fortified with Grapefruit Peel Extract.

Grapefruit peel contains a high concentration of naringin- a potent antioxidant with strong bioactive properties. In this study, a new type of functional chocolate fortified with grapefruit peel extract and different concentrations of aqueous methanol and ethanol were evaluated as extraction solvents. A new high-performance liquid chromatography (HPLC) method to analyze the naringin content of the fortified chocolates was developed with a recovery of 107% ± 3.1% and repeatability below 3.5%. A sensory evaluation was conducted to assess the preference for the chocolates among individuals who self-described a preference for bitter flavors. No significant preference was observed in the cases of astringency and aftertaste while the increased bitterness proved to be favorable. However, taste, flavor and overall acceptability were regarded somewhat less favorably. While chocolate proved to be a satisfactory carrier for naringin and had several enjoyable characteristics, further research may focus on improving the organoleptic properties of chocolates fortified by naringin.

N, S, O Self-Doped Carbon Derived from Grapefruit Peel for High-Performance Supercapacitors.

The development of high-capacity carbon for supercapacitors is highly desirable but challenging. In this work, we design a N, S, O self-doped carbon electrode (NSOC-800) with high capacitance and good stability via the carbonization of grapefruit peel via a one-step KOH activation method without extra dopants. The existence of heteroatoms enables the NSOC-800 to have a high specific capacitance of 280 F/g and a great cycling performance, with 90.1% capacitance retention after 5000 cycles. Moreover, the symmetric supercapacitor with NSOC-800 electrodes delivers a maximum energy density of 5 Wh/kg with a power density of 473 W/kg. Such a promising method to achieve carbon materials with self-doping heteroatwoms is of great significance for developing highly efficient electrodes for energy storage devices.

Preparation of Acetylated Grapefruit Peel Polysaccharide.

Grapefruit peel polysaccharide has antioxidant, antitumor, hypoglycemic and other biological activities, and chemical modification can further improve the properties of the polysaccharide. Acetylation modification of polysaccharides has the advantages of simple operation, low cost and little pollution, and is widely used at present. Different degrees of acetylation modification have different effects on the properties of polysaccharides, so it is necessary to optimize the preparation technology of acetylated grapefruit peel polysaccharides. In this article, acetylated grapefruit peel polysaccharide was prepared by acetic anhydride method. With the degree of acetyl substitution as the evaluation index, combined with the analysis of sugar content and protein content in the polysaccharide before and after modification, the effects of three feeding ratios of 1:0.6, 1 : 1.2 and 1 : 1.8 (polysaccharide: acetic anhydride, mass/volume) on acetylation modification were explored through single factor experiments. The results showed that the optimum ratio of material to liquid for acetylation modification of grapefruit peel polysaccharide was 1:0.6. Under these conditions, the degree of substitution of acetylated grapefruit peel polysaccharide was 0.323, the sugar content was 59.50 % and the protein content was 1.038 %. The results provide some reference for the study of acetylated grapefruit peel polysaccharide.

Comparison of chitosan and gelatin-based films and application to antimicrobial coatings enriched with grapefruit seed extract for cherry tomato preservation.

Bio-based single, composite, and bilayer edible films were developed based on chitosan and gelatin, including grapefruit seed extract (GSE) as an antimicrobial agent. The physicochemical and antimicrobial properties of films were analyzed, and it was found that compounding and laminating two polymers could enhance their physicochemical properties. The composite film was strong, endurable, and flexible compared with the single ones. In addition, the composite and bilayer films had lower water vapor permeability than the single ones. Edible films and coatings with GSE presented a greater bactericidal effect than the inactive ones. In addition, the hardness, weight, and color changes of the coated cherry tomatoes during 7-day storage did not differ, whereas a bacterial reduction against Salmonella Typhimurium was revealed. Taken together, composite and bilayer films with CH and GL and enriched with GSE were developed for food packaging applications, and it showed improved mechanical, water barrier, and antimicrobial properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01254-9.

Role of hydraulic traits in stomatal regulation of transpiration under different vapour pressure deficits across five Mediterranean tree crops.

The differential stomatal regulation of transpiration among plant species in response to water deficit is not fully understood, although several hydraulic traits have been reported to influence it. This knowledge gap is partly due to a lack of direct and concomitant experimental data on transpiration, stomatal conductance, and hydraulic traits. We measured sap flux density (Js), stomatal conductance (gs), and different hydraulic traits in five crop species. Our aim was to contribute to establishing the causal relationship between water consumption and its regulation using a hydraulic trait-based approach. The results showed that the species-specific regulation of Js by gs was overall coordinated with the functional hydraulic traits analysed. Particularly relevant was the negative and significant relationship found between the Huber value (Hv) and its functional analogue ratio between maximum Js and gs (Jsmax/gsmax) which can be understood as a compensation to maintain the hydraulic supply to the leaves. The Hv was also significantly related to the slope of the relationship between gs and Js response to vapour pressure deficit and explained most of its variability, adding up to evidence recognizing Hv as a major trait in plant water relations. Thus, a hydraulic basis for regulation of tree water use should be considered.