Nanoformulation of drugs is a highly important task in medicine to improve their solubility and dissolution. The lipid-based drug delivery systems (LBDDS) facilitate the encapsulation of a broad range of therapeutic agents. Preparation techniques have evolved from simple laboratory "bench" methods to sophisticated, high-throughput technologies. More recently, methods that offer precision, reproducibility, and scalability are in focus as the microfluidics. To the best of our knowledge, we are the first to demonstrate an optimized fabrication protocol of lipid-based colloidal carriers using a low-cost cleaned asolectin (ASO) with a continuously operating basic flow system that offers precise control and high reproducibility. We pointed out how the hydrodynamic diameter, stability, and encapsulation efficiency (EE) can be highly controlled by the initial parameters (flow conditions, pH, storage time, dialysis time, etc.). Tocopherol (TP) and polyvinyl alcohol (PVA) were used as the model drug and stabilizer, respectively. Drug-free carriers having 130 180 nm diameter and 190 300 nm drug-loaded colloids can be fabricated, and it can be confirmed that by nanoformulation the aqueous solubility of TP was increased by 17 20 times. We evaluated the effect of NaCl concentration and pH on the colloids’ stability. The application of the PVA stabilizer slightly increases the EE from 68.6% for ASO/TP to 78.4% for ASO/TP/PVA at a dialysis time of 120 min, and it also enables significant drug retention. In addition to diffusion-controlled processes, the presence of the stabilizer increases the role of carrier erosion, according to the fitting of the dissolution data with different kinetic models. • The flow technique is capable of preparing asolectin-based drug carrier particles. • Size, stability, and formulation ability can be greatly controlled by flow conditions. • Lipid-based nanoformulation of tocopherol increases its water solubility by ∼20 times. • Use of polyvinyl alcohol as a stabilizer enhances the formulation and drug retention.

Background: Flaxseed (Linum usitatissimum L.) Oil (FSO) is valued for its high content of Polyunsaturated Fatty Acids (PUFAs) and natural antioxidants but is susceptible to oxidative degradation during processing. The objective of this study was to evaluate the effects of microwave heat treatment on the compositional characteristics, oxidation stability, and sensory quality of Golden and Brown FSOs. Methods: Two flaxseed varieties were roasted at 2450 MHz for 3, 6, 9, and 12 min. The proximate composition (moisture, ash, fiber, protein, and oil), fatty acid profile, Tocopherol (TC) and Total Phenolic Contents (TPC), and oxidative stability parameters (Peroxide Value [PV], Acid Value [AV], Anisidine Value [AnV], Iodine Value [IV], and Malondialdehyde [MDA]) were determined using standard AOAC and ISO methods. Sensory attributes (color, transparency, odor, flavor, and overall acceptability) were evaluated by a trained panel using a 5-point hedonic scale. Results: Microwave roasting affected FSO composition and quality in a time-dependent manner. Fiber, ash, and protein did not change significantly, whereas moisture decreased from 6.24% to 3.51% (Golden) and 6.02% to 3.03% (Brown), and FSO content increased from 32.54% to 35.38% and 33.43% to 36.60%, respectively. Saturated Fatty Acids (SFA) were increased and Polyunsaturated Fatty Acids (PUFA) decreased with prolonged roasting, suggesting partial oxidation of Unsaturated Fatty Acids (USFA). Tocopherol (TC) and Total Phenolic Contents (TPC) were decreased, while oxidative parameters ((Peroxide Value [PV], Acid Value [AV], Anisidine Value [AnV], and Malondialdehyde [MDA])) increased and Iodine Value (IV) decreased over time. Sensory evaluation was highest at 3 min, suggesting short-term roasting optimally balances oil yield, nutritional quality, and sensory attributes. Conclusion: Optimized control of microwave roasting can optimize FSO production, balancing nutritional quality, sensory properties, and industrial applicability.

ABSTRACT The objective of this work was to generate and characterize complexes of quinoa proteins (QP) with either resveratrol (RSV) or tocopherol (TOC) whose dimensions fell into the nanoscale. The QP‐based nanocomplexes characterization was carried out jointly with encapsulation efficiency determination. Fourier‐Transform Infrared Spectroscopy (FTIR) showed no covalent bond formation and indicated that the protein's secondary structure was modified. Transmission Electron Microscopy (TEM) images and Dynamic Light Scattering (DLS) measurements confirmed that the addition of bioactive compounds did not substantially alter the protein's original size. A consistent particle diameter of 100 nm was observed in both types of nanocomplexes with and without RSV and TOC. The antioxidant capacity of nanocomplexes was analyzed after an in vitro simulated digestion process, showing an increase in this property postdigestion. These nanocomplexes hold great potential as functional ingredients.

Oxidative stress induced by excessive hydrogen peroxide (H2O2) is a critical pathological factor in skin aging, inflammatory disorders, and photodamage. While tocopherol (TCP) is a gold-standard antioxidant in cosmetics, its potential in H2O2-responsive systems remains underexplored. In this study, we report the design and characterization of ditocopheryl peroxalate (TOT), a novel tocopherol dimer linked via a H2O2-cleavable peroxalate linkage. TOT remains chemically stable under physiological conditions but undergoes selective chemiluminescence-like degradation upon exposure to H2O2, simultaneously scavenging H2O2 and liberating two TCP molecules. Notably, TOT demonstrated superior H2O2-scavenging efficiency and enhanced antioxidant and anti-inflammatory effects in H2O2-stimulated cells compared to monomeric TCP, while maintaining excellent biocompatibility. Structural analysis revealed that the rigid, linear configuration of TOT facilitates seamless integration into dipalmitoylphosphatidylcholine (DPPC) bilayers, yielding highly stable H2O2-responsive liposomes. These findings highlight TOT as a sophisticated multifunctional antioxidant platform for advanced cosmeceutical applications targeting photo-induced oxidative damage.

Poultry housing includes unavoidable stressors that impair birds' welfare and health. Global policies are banning antimicrobial growth promoters mainly due to antimicrobial resistance. Antioxidants modulate immunity by reducing oxidative stress, which impairs immune function. Thymol (THY), tocopherol (TOC) and ascorbyl palmitate (AP) have been studied for their antioxidant, antimicrobial and anxiety/fear-reducing properties. However, their effects on immune function and stress responses in broilers require further investigation. This study assesses whether dietary THY or a TOC and AP mix modulates immune and chronic stress-related responses in broilers. Cobb-500 chicks (n=960) were assigned to one of 6 dietary treatments: (1) Basal (control), (2) Promotor (Basal+flavomycin), (3) BHT (Basal+butylated hydroxytoluene), (4) Promotor-BHT (Basal+flavomycin+BHT), (5) THY (Basal+thymol) and (6) TOC-AP (Basal+tocopherol+AP). Immune and stress parameters were evaluated, including inflammatory response to phytohemagglutinin-P (PHA-P), antibody production against sheep red blood cells (SRBC) and heterophil-to-lymphocyte (H/L) ratio. Supplementation did not affect the PHA-P inflammatory response (p=0.72) but influenced SRBC antibody production and H/L ratio (p<0.003). Broilers supplemented with THY or TOC-AP exhibited significantly lower antibody responses, potentially avoiding an energy-demanding acquired immune activation. Additionally, both groups showed significantly lower H/L ratios, suggesting that these supplements may help mitigate physiological stress induced by routine husbandry practices. These findings provide evidence that THY and TOC-AP may serve as natural alternative to synthetic additives for improving welfare and mitigating stress-induced immune imbalance under commercial rearing conditions.

Background/Objectives: This study aimed to evaluate the therapeutic effects of combined 5% lifitegrast (LF) and tocopherol (TCP) eye drops in a murine experimental dry eye (EDE) model. Methods: Female C57BL/6 were divided into seven groups: untreated controls, EDE control, EDE + 0.05% cyclosporin A (CsA), EDE + tocopherol (TCP), EDE + 5% LF, EDE + 5% LF + TCP (once daily), and EDE + 5% LF + TCP (twice daily). Clinical parameters (tear volume, tear break-up time (TBUT), corneal fluorescein staining score (CFSS), tear film lipid layer grade (TFLLG)) were assessed on days 7 and 14. Goblet cell density in the conjunctiva, CD4+ IFN-γ+ T cells, interleukin levels, reactive oxygen species (ROS) levels, and corneal apoptotic cells were analyzed on day 14. Results: Monotherapy with 0.05% CsA and LF showed improvements in all clinical parameters compared to the EDE control (p < 0.05). Combination therapy groups demonstrated superior improvements in clinical parameters compared to the EDE control, 0.05% CsA, and 5% LF groups. CD4+ IFN-γ+ T cell percentages and ROS levels in the cornea and conjunctiva were markedly reduced in the combination groups compared with the 0.05% CsA and 5% LF groups (p < 0.01). Furthermore, corneal apoptotic cells significantly decreased in the combination groups compared to the 0.05% CsA and TCP groups (p < 0.05). Conclusions: Combined 5% LF and TCP eye drops improved tear film parameters and reduced inflammatory and oxidative stress markers. The combination therapy can mitigate ocular surface damage by managing inflammation and oxidative stress in dry eye.

The objective of the present contribution was to design and characterize resveratrol (RSV) and tocopherol (TOC) loaded quinoa protein (QP) nanocomplexes, their antioxidant and antiradical functionality were also evaluated. QP intrinsic fluorescence spectra showed a quenching effect exerted by RSV and TOC, demonstrating protein-bioactive compounds interactions. Stern-Volmer and Scatchard models application confirmed the static quenching effect and allowed to obtain parameters that described the QP-RSV or QP-TOC complexation process. Isothermal titration calorimetry allowed obtaining thermodynamic parameters to describe the interaction between RSV or TOC with QP. Protein aggregates up to 40nm in diameter were induced by bioactive compounds as detected by atomic force microscopy. QP-RSV and QP-TOC nanocomplexes showed additive effect in their antioxidant capacity. These nanocomplexes could constitute a real platform for the design of functional ingredients.

Nanocomplexes, which possess immense potential to function as nanovehicles, can link diverse ligand compounds. The objective of the present study was to design and characterize resveratrol (RSV)- and tocopherol (TOC)-loaded 11S quinoa seed protein nanocomplexes. Firstly, molecular docking was performed to describe the probable binding sites between protein and ligands, and binding energies of -5.6 and -6.2 kcal/mol were found for RSV and TOC, respectively. Isothermal titration calorimetry allowed us to obtain the thermodynamic parameters that described the molecular interactions between RSV or TOC with the protein, finding the complexation process to be exothermic and spontaneous. 11S globulin intrinsic fluorescence spectra showed quenching effects exerted by RSV and TOC, demonstrating protein-bioactive compound interactions. The application of Stern-Volmer, Scatchard, and Förster resonance energy transfer models confirmed static quenching and allowed us to obtain parameters that described the 11S-RSV and 11S-TOC complexation processes. RSV has a higher tendency to bind 11S globulin according to ITC and fluorescence analysis. Secondly, the protein aggregation induced by bioactive compound interactions was confirmed by dynamic light scattering and atomic force microscopy, with diameters <150 nm detected by both techniques. Finally, it was found that the antioxidant capacity of a single 11S globulin did not decrease; meanwhile, it was additive for 11S-RSV. These nanocomplexes could constitute a real platform for the design of nutraceutical products.

Introduction: This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. Methods: Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. Results: FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. Conclusion: The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.

Exploring somatic embryogenesis in Ajuga multiflora Bunge: Profiling lipophilic metabolites via HPLC, GC-FID, and GCMS– analysis

Abstract The objective of the present contribution was to design and characterize resveratrol (RSV) and tocopherol (TOC) loaded quinoa protein (QP) nanocomplexes, their antioxidant and antiradical functionality were also evaluated. QP intrinsic fluorescence spectra showed a quenching effect exerted by RSV and TOC, demonstrating protein-bioactive compounds interactions. Stern-Volmer and Scatchard models application confirmed the static quenching effect and allowed to obtain parameters that described the QP-RSV or QP-TOC complexation process. Isothermal titration calorimetry allowed obtaining thermodynamic parameters to describe the interaction between RSV or TOC with QP. Protein aggregates up to 40 nm in diameter were induced by bioactive compounds as detected by atomic force microscopy. QP-RSV and QP-TOC nanocomplexes showed additive effect in their antioxidant capacity. These nanocomplexes could constitute a real platform for the design of functional ingredients.

Drum drying of whole maize flour enhances bioaccessibility of zeaxanthin, α-tocopherol, phytosterols, phenolics and flavonoids

Metabolic syndrome (Met-S) reflects a congregate of metabolic derangements including central obesity, hypertension, insulin resistance, dyslipidemia leading to enhanced risk of developing cardiovascular disease and diabetes. Both tocopherol (TCP) and tocotrienol (T3) have significant role in Met-S. However, it is still unclear regarding better clinical efficacy of either one in management of Met-S. This review compares clinical efficacy of different isomers of tocopherol with tocotrienol in stewardship of Met-S by search of human clinical studies only. Literature search was conducted till 20th May 2023 on PubMed, google scholar, open google search, pak- medinet and Cochrane data-bases. So far evidence revealed that Tocotrienol have been found safer and more beneficial as compared to tocopherol, having great potential in improving diabetes, hypertension and hyperlipidemia in Met-S patients and robust candidate for further future research regarding ameliorating obesity in metabolic syndrome. Keywords: Metabolic Syndrome, Tocopherol, Tocotrienol, Obesity, Diabetes, Dyslipidemias. How to Cite This: Rafique S, Khan DA, Farhat K, Noor M, Khan MA, Sharif M. Tocopherol Vs Tocotrienol (Vitamin E) in the Management of Metabolic Syndrome. Isra Med J. 2023; 15(2): 74-77.DOI: https://doi.org/10.55282/imj.ra52

This study aimed to fabricate new variations of glycerol-based polyesters by grafting poly(glycerol adipate) (PGA) with hydrophobic bioactive moieties, tocopherol (TOC), and cholesterol (CHO). Their effects on nanoparticle (NP) formation, drug release, and cellular responses in cancer and normal cells were evaluated. CHO and TOC were successfully grafted onto PGA backbones with 30% and 50% mole grafting. Increasing the percentage of mole grafting in both molecules increased the glass transition temperature and water contact angle of the final polymers but decreased the critical micelle concentration of the formulated particles. PGA-TOC NPs reduced the proliferation of MDA-MB-231 cancer cells. However, they enhanced the proliferation of primary dermal fibroblasts within a specific concentration range. PGA-CHO NPs minimally affected the growth of cancer and normal cells. Both types of NPs did not affect apoptosis or the cell cycle of cancer cells. PGA-CHO and PGA-TOC NPs were able to entrap SN-38, a hydrophobic anticancer drug, with a particle size <200 nm. PGA-CHO NPs had a higher drug loading capacity and a greater drug release than PGA-TOC NPs. However, SN-38-loaded PGA-TOC NPs showed higher toxicity than SN-38 and SN-38-loaded PGA-CHO NPs due to the combined effects of antiproliferation and higher cellular uptake. Compared with SN-38, the drug-loaded NPs more profoundly induced sub-G1 in the cell cycle analysis and apoptosis of cancer cells in a similar pattern. Therefore, PGA-CHO and PGA-TOC polymers have potential applications as delivery systems for anticancer drugs.

Diabetic neuropathy (DN) causes sensory dysfunction, such as numbness, tingling, or burning sensations. Traditional medication may not ease pain and discomfort, but natural remedies such as Berberine (BR) and vitamin E or Tocopherol (TOC) have therapeutic potential to reduce inflammation while improving nerve function. Novel substances offer a more potent alternative method for managing severe chronic neuropathic pain that does not react to standard drug therapy by targeting various pathways that regulate it. Rats with diabetic control received oral doses of BR + TOC that showed significant changes in serum insulin levels compared to DN controls after 90 days, suggesting a decrease in sensitivity to painful stimuli partly by modulating the oxidative stress of the inflammatory pathway such as TNF-α suppression or stimulation of TNF-α depending on the amount of dose consumed by them. NF-kB also played its role here. Administering doses of BR and TOC reduced heightened levels of NF-kB and AGEs, effectively counteracting inflammation-targeted key factors in diabetes, promising possibilities for the benefits of these molecules revealed through in vivo investigation. In summary, treating neuropathy pain with a more comprehensive and organic approach can involve harnessing the powerful capabilities of BR and TOC. These compounds have been found to not only considerably decrease inflammation but also provide effective nerve protection while enhancing overall nerve function. With their multifunctional impacts on various neuropathic pain pathways in the body, these naturally occurring substances offer an exciting possibility for those who encounter high levels of neuropathic distress that do not respond well to conventional medication-centred therapies.

ABSTRACT: The production of bioactive food is one of the goals of agriculture. Sprouts used for human consumption are an efficient way to increase the intake of essential nutrients, such as minerals, vitamins, and other bioactive compounds. The use of elicitors can increase the nutritional value of these products. Biomass production, phenolic compound content, and antioxidant activity of mung bean sprouts (Vigna radiata L.) after elicitation were examined in this study. Mung bean sprouts were treated with salicylic acid (SA), ascorbic acid (AA), and tocopherol (TOC) at different concentrations and numbers of applications. Shoot and root lengths and dry mass were measured on five-day-old sprouts. Total phenol content and antioxidant activity were determined using the DPPH assay on dried ethanolic extracts. Total soluble protein content and superoxide dismutase activity were measured in frozen hypocotyls. All elicitors stimulated the antioxidant functions of sprouts and, at the highest concentrations, reduced the biometric parameters; therefore, lower concentrations were better. For the first time, a balance between elicitor concentration and application in instalments was achieved to maintain the production of sprouts with enhanced nutritional characteristics.

UPLC/ESI-Q-TOF-MS analysis of (poly)phenols, tocols and amino acids in Chaenomeles leaves versus in vitro anti-enzyme activities

Scavenging of superoxide radical anion (O2•−) by tocopherols (TOH) and related compounds was investigated on the basis of cyclic voltammetry and in situ electrolytic electron spin resonance spectrum in N,N-dimethylformamide (DMF) with the aid of density functional theory (DFT) calculations. Quasi-reversible dioxygen/O2•− redox was modified by the presence of TOH, suggesting that the electrogenerated O2•− was scavenged by α-, β-, γ-TOH through proton-coupled electron transfer (PCET), but not by δ-TOH. The reactivities of α-, β-, γ-, and δ-TOH toward O2•− characterized by the methyl group on the 6-chromanol ring was experimentally confirmed, where the methyl group promotes the PCET mechanism. Furthermore, comparative analyses using some related compounds suggested that the para-oxygen-atom in the 6-chromanol ring is required for a successful electron transfer (ET) to O2•− through the PCET. The electrochemical and DFT results in dehydrated DMF suggested that the PCET mechanism involves the preceding proton transfer (PT) forming a hydroperoxyl radical, followed by a PCET (intermolecular ET–PT). The O2•− scavenging by TOH proceeds efficiently along the PCET mechanism involving one ET and two PTs.

Purpose To investigate the efficacy of topical application of 3% diquafosol sodium (DQS) and tocopherol (TCP) acetate mixtures in a mouse model of experimental dry eye (EDE). Methods After exposure to desiccating stress for 5 days, eye drops consisting of 3% DQS alone, 0.01% TCP alone, or 3% DQS and 0.005% or 0.01% TCP mixture were applied for the treatment of EDE. Tear volume, tear film break-up time (TBUT), corneal fluorescein staining scores (CFSS), and tear film lipid layer grades (TFLLG) were measured at 0, 5 and 10 days after treatment. The 2',7'-dichlorodihydrofluorescein diacetate assay (DCFDA) for reactive oxygen species (ROS) production, enzyme-linked immunosorbent assay (ELISA) for malondialdehyde (MDA), and flow cytometry for CD4 + interferon (IFN)-γ+ T cells were evaluated on the ocular surface at 10 days after treatment. In addition, levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and chemokine CC motif ligand 4 (CCL4) in the conjunctiva were measured using a multiplex immunobead assay, and conjunctival goblet cells were counted by periodic acid-Schiff staining at 10 days after treatment. Results Both the TCP mixture groups indicated a significant improvement in TBUT, ROS production, and MDA concentrations compared to those in the DQS alone group. Furthermore, the 0.01% TCP mixture group also showed higher tear film lipid layer grades and conjunctival goblet cell density and lower corneal fluorescein staining scores, number of CD4 + IFN-γ+ T cells, and levels of TNF-α, IL-1β, and CCL4 than the DQS alone group (P < 0.05). Conclusions Application of eye drops containing the mixture of DQS and TCP could stabilize the tear film lipid layer, improve TBUT and corneal epithelial damages, decrease ROS production, inflammatory molecules, and T cells, and increase conjunctival goblet cell density on the ocular surface. Topical DQS and TCP mixtures may have a greater therapeutic effect on clinical signs, oxidative damage, and inflammation of dry eye than DQS eye drops.

Flaxseed is a plant that grows and is cultivated in more than 50 countries; the main flax producer countries are Canada, China, the United States, and India. The purpose of the present study was to overview the source, chemical compounds, and mechanisms of the therapeutic effects of this valuable plant. For writing this manuscript, we made a list of relevant keywords and phrases, and then we started searching for studies in PubMed, Scopus, and Web of Science databases. The main constituents of flaxseed include lipids, proteins, lignans, fibers, and minerals. Flaxseed is full of antioxidants such as tocopherols, betacarotene, cysteine, and methionine which result in a decrease in blood pressure, heart disease, hepatic and neurological disorders, and increased insulin sensitivity. Flaxseed is commonly used for its antidiabetic and anticancer activities and also it is beneficial for cardiovascular, gastrointestinal, hepatic, urological, and reproductive disorders, and because of these beneficial effects, it is recognized as a medical plant.