Development of hemp seed oil nanoemulsions loaded with ascorbyl palmitate: Effect of operational parameters, emulsifiers, and wall materials.

The perceived health properties of hemp seed oil, as one of the few plant-basedsources of omega-3 and omega-6 fatty acids with an ideal ratio of 1:3, suggest its incorporation in food-grade emulsions to improve its water solubility and oxidative stability. The current research's main aim was nanoemulsification of hemp seed oil using the oil-in-water emulsification method followed by ultrasonication. The entrapment efficiency of the nanoemulsions for antioxidant ascorbyl palmitate and its impact on oxidative stability of the oil was also evaluated. Gum arabic: maltodextrin in 75:25 ratio could result in nanoemulsion with entrapment efficiency of 97.10 % for ascorbyl palmitate and radical scavenging activity of oil-soluble bioactives of 92.13 %. Moreover, incorporation of ascorbyl palmitate could effectively retard the oxidation, specifically in nanoemulsions containing gum Arabic. The optimum formulation of nanoemulsion having an average droplet size of 293 nm can be applied as an ideal vegetarian source of omega-3 fatty acids.

Natural 8-C-ascorbyl-(-)-epigallocatechin as antidiabetic agent: α-glucosidase and PTP-1B signaling pathway dual regulators.

α-Glucosidase and protein tyrosine phosphatase 1B (PTP1B) signaling pathway dual regulators decrease postprandial blood glucose levels and improve insulin sensitivity, making it a new treatment strategy for type 2 diabetes. This study examined in vitro antidiabetic activities of 8-C-ascorbyl-(-)-epigallocatechin (AE), found in oolong tea. AE inhibited α-glucosidase (IC50 = 142.8 µM) with activity higher than that of acarbose (IC50 = 250.2 µM). AE significantly promoted glucose-consumption and activated the insulin signaling pathway through enhancing the protein levels of p-GSK3ß and p-Akt and inhibiting the expression of PTP1B, along with slightly inhibitory activity against PTP1B. Docking analysis showed AE inhibited α-glucosidase activity via binding to the catalytic site through hydrogen bonds and Pi-Pi interactions, as well as a good shape match to the active pocket. In addition, AE could relieve oxidative damage and possessed good antioxidant capacity. Taken together, the results of this study indicate that AE exhibits antidiabetic activity in vitro, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.

A ternary system of α-tocopherol with phosphatidylethanolamine and l-ascorbyl palmitate in bulk oils provides antioxidant synergy through stabilization and regeneration of α-tocopherol.

The stabilization of fats and oils against oxidative lipid deterioration is still a great challenge. The synergistic interaction between phospholipids, l-ascorbate, and tocopherols have not yet been comprehensively understood. The mechanism of the synergistic antioxidant effect of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (PE) in mixtures with l-ascorbyl palmitate (AP) and α-tocopherol (α-Toc) was investigated in an ethyl linoleate model and sunflower oil at 110 °C. The mixture of PE, AP, and α-Toc is stabilized through continuous regeneration of α-Toc from its oxidation product α-tocopherylquinone (α-TQ). This reaction is catalyzed by acids and proceeded through the formation of the α-tocopherone ion (T+) as an intermediate product. In addition to the direct reduction of T+ by AP, PE can also cause regeneration indirectly by reacting with dehydroascorbyl palmitate (DHAP) or other tricarbonyl compounds to form amino reductones. PE and AP undergo an amino-carbonyl reaction to form the condensate PE(AP)2.

Wharton's jelly mesenchymal stem cells embedded in PF-127 hydrogel plus sodium ascorbyl phosphate combination promote diabetic wound healing in type 2 diabetic rat.

BACKGROUND: Diabetic cutaneous ulcers (DCU) are a complication of diabetes with diabetic foot ulcers being the most common, and the wounds are difficult to heal, increasing the risk of bacterial infection. Cell-based therapy utilizing mesenchymal stem cells (MSCs) is currently being investigated as a therapeutic avenue for both chronic diabetic ulcers and severe burns. Wharton's jelly mesenchymal stem cell (WJMSC) with PF-127 hydrogel and sodium ascorbyl phosphate (SAP) improved skin wound healing in mice. Whether this combination strategy is helpful to diabetic ulcers wound healing remains to be explored. METHODS: Firstly, the WJMSCs embedded in PF-127 and SAP combination were transplanted onto excisional cutaneous wound bed in type 2 diabetic Sprague Dawley (SD) rats. Two weeks after transplantation, the skin tissue was collected for histological and immunohistochemical analysis. Further, overexpressing-EGFP WJMSCs were performed to investigate cell engraftment in the diabetic cutaneous ulcer. The apoptosis of WJMSCs which encapsulated with combination of PF-127 and SAP was detected by TUNEL fluorescence assay and RT-PCR in vitro. And the mitochondrial damage induced by oxidative stress assessed by MitoTracker and CMH2DCFDA fluorescence assay. RESULTS: In diabetic cutaneous wound rat model, PF-127 plus SAP-encapsulated WJMSCs transplantation promoted diabetic wound healing, indicating improving dermis regeneration and collagen deposition. In diabetic wound healing, less pro-inflammatory M1 macrophages, more anti-inflammatory M2 tissue-healing macrophages, and neovascularization were observed in PF-127 + SAP + WJMSCs group compared with other groups. SAP supplementation alleviated the apoptosis ratio of WJMSCs embedded in the PF-127 in vitro and promoted cell survival in vivo. CONCLUSION: PF-127 plus SAP combination facilitates WJMSCs-mediated diabetic wound healing in rat through promoting cell survival, the macrophage transformation, and angiogenesis. Our findings may potentially provide a helpful therapeutic strategy for patients with diabetic cutaneous ulcer.

Understanding the Therapeutic Potential of Ascorbic Acid in the Battle to Overcome Cancer.

Cancer, a fatal disease, is also one of the main causes of death worldwide. Despite various developments to prevent and treat cancer, the side effects of anticancer drugs remain a major concern. Ascorbic acid is an essential vitamin required by our bodies for normal physiological function and also has antioxidant and anticancer activity. Although the body cannot synthesize ascorbic acid, it is abundant in nature through foods and other natural sources and also exists as a nutritional food supplement. In anticancer drug development, ascorbic acid has played an important role by inhibiting the development of cancer through various mechanisms, including scavenging reactive oxygen species (ROS), selectively producing ROS and encouraging their cytotoxicity against tumour cells, preventing glucose metabolism, serving as an epigenetic regulator, and regulating the expression of HIF in tumour cells. Several ascorbic acid analogues have been produced to date for their anticancer and antioxidant activity. The current review summarizes the mechanisms behind ascorbic acid's antitumor activity, presents a compilation of its derivatives and their biological activity as anticancer agents, and discusses delivery systems such as liposomes, nanoparticles against cancer, and patents on ascorbic acid as anticancer agents.

Production of ascorbic acid, total protein, callus and root in vitro of non-heading Chinese cabbage by tissue culture.

The objective of the present work was the selection of cultivar, suitable medium and explant type for callus, root production, ascorbic acid, total ascorbic acid, dehydroascorbic and total protein of non-heading Chinese cabbage in two cultivars 'Caixin' and 'Suzhouqing'. We compared 10 types of MS media supplemented with 0.0, 1.0, 2.0 and 3.0 mg/l TDZ; 0.0, 0.25, 0.50 and 1.0 mg/l NAA and 0.0, 5.0, 7.5 and 9.0 mg/l AgNO3 and 5 kinds of explants as embryo, leaf, root, cotyledon and hypocotyl. Maximum frequency of callus fresh weight was recorded with hypocotyl explant, which were cultured on MS + 2.0 mg/l TDZ + 1.0 mg/l NAA + 9.0 mg/l AgNO3 in 'Suzhouqing', optimum callus dry weight was obtained on the same media. The highest result for root fresh and dry weight recorded with 'Caixin' with MS + 3.0 mg/l TDZ + 1.0 mg/l NAA + 9.0 mg/l AgNO3 when we used embryo as explant. The highest ascorbic acid content was found with callus cultured on MS + 1.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO3, when used leaf explant in 'Caixin' or root in 'Suzhouqing', and there were no significant difference between them. While the highest value of total AsA content was registered with callus cultured on MS + 2.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO3 extracted from cotyledon in 'Caixin'. The highest content of DHA was registered with MS + 2.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO3 with cotyledon in 'Caixin'. Also, in 'Caixin' MS + 3.0 mg/l TDZ + 0.25 mg/l NAA + 5.0 mg/l AgNO3 recorded the highest value of total protein content with embryo explant.

Improving the oxidative stability and lengthening the shelf life of DHA algae oil with composite antioxidants.

Based on various antioxidant mechanisms, four kinds of antioxidants including ascorbyl palmitate (AP), vitamin E (VE), phytic acid (PA) and one of the polyphenols (antioxidant of bamboo leaves, tea polyphenol palmitate or tea polyphenols (TP)) were used in combination to improve oxidative stability of docosahexaenoic acid (DHA) algae oil. To achieve the best effect, the formulations and mixture ratios of the antioxidant combinations were optimized. The effects were monitored by peroxide value, thiobarbituric acid-reactive substances, acid value, free radicals, Rancimat induction time and fatty acid composition of DHA algae oil undergoing accelerated storage. Finally, the DHA algae oil containing 80 mg/kg AP, 80 mg/kg VE, 40 mg/kg PA and 80 mg/kg TP had the highest oxidative stability. Furthermore, the shelf life of DHA algae oil containing the optimum composite antioxidant was predicted by using accelerated shelf life testing coupled with Arrhenius model, which was 3.80-fold longer than the control sample.

The Influence of Cell Culture Density on the Cytotoxicity of Adipose-Derived Stem Cells Induced by L-Ascorbic Acid-2-Phosphate.

Ascorbic acid-2-phosphate (A2-P) is an oxidation-resistant derivative of ascorbic acid that has been widely employed in culturing adipose-derived stem cells (ASCs) for faster expansion and cell sheet formation. While high dose ascorbic acid is known to induce cellular apoptosis via metabolic stress and genotoxic effects, potential cytotoxic effects of A2-P at high concentrations has not been explored. In this study, the relationship between ASC seeding density and A2-P-induced cytotoxicity was investigated. Spheroid-derived ASCs with smaller cellular dimensions were generated to investigate the effect of cell-cell contact on the resistance to A2-P-induced cytotoxicity. Decreased viability of ASC, fibroblast, and spheroid-derived ASC was noted at higher A2-P concentration, and it could be reverted with high seeding density. Compared to control ASCs, spheroid-derived ASCs seeded at the same density exhibited decreased viability in the A2-P-supplemented medium. The expression of antioxidant enzymes (catalase, SOD1, and SOD2) was enhanced in ASCs at higher seeding densities. However, their enhanced expression in spheroid-derived ASCs was less evident. Furthermore, we found that co-administration of catalase or N-acetylcysteine nullified the observed cytotoxicity. Collectively, A2-P can induce ASC cytotoxicity at higher concentrations, which can be prevented by seeding ASCs at high density or co-administration of another antioxidant.

Ascorbic acid derivative-loaded modified aspasomes: formulation, in vitro, ex vivo and clinical evaluation for melasma treatment.

Vitamin C (L-Ascorbic acid) has many favourable effects on the skin such as antioxidant, anti-aging and whitening effects. Its instability and low permeability limit its pharmaceutical use in cosmetic and dermatological products. Instead, Mg ascorbyl phosphate (MAP), an ascorbic acid derivative, has the same effect with higher stability is being used. In this work, a vesicular system, aspasomes, containing MAP was developed and evaluated. Aspasomes are multilayered vesicles formed by amphiphiles molecules, Ascorbyl palmitate (ASP), in combination with cholesterol and charged lipids for drug encapsulation. Here, we investigated the use of lecithin instead of the charged lipid dicetyl phosphate for aspasomes development. Nine formulations were prepared and evaluated for their entrapment efficiency, particle size, polydispersity index (PDI) and zeta potential. Their entrapment efficiency ranged from 33.00 ± 2.27 to 95.18 ± 1.06, while their particle size was from 373.34 ± 60.85 to 464.37 ± 93.46 nm with acceptable PDI (from 0.212 ± 0.068 to 0.351 ± 0.061) and zeta potential (from -37.52 ± 2.42 to -50.36 ± 1.82). Three formulations were selected and evaluated for their drug release, permeation and retention into skin. One formulation was selected to be formulated as aspasomal topical cream and gel. The aspasomal cream was found to have enhanced drug permeation and skin retention over the aspasomal gel as well as the aspasomes formulation. MAP aspasomal cream was evaluated clinically as an effective treatment for melasma against 15% trichloroacetic acid (TCA) and the results recorded that the aspasomal cream showed the greatest degree of improvement regarding the hemi-MASI scores with 35% of patients rating it as excellent treatment. The study showed that MAP aspasomal cream can be considered a novel treatment of melasma which is free of side effects. Its efficacy as a monotherapy is superior to that of chemical peeling using 15% TCA.

Ascorbic Acid 2-Glucoside Stably Promotes the Primitiveness of Embryonic and Mesenchymal Stem Cells Through Ten-Eleven Translocation- and cAMP-Responsive Element-Binding Protein-1-Dependent Mechanisms.

Aims: The naive or primitive states of stem cells (SCs) residing in specific niches are unstable and difficult to preserve in vitro. Vitamin C (VitC), in addition to suppressing oxygen radicals, exerts pleiotropic effects to preserve the core functions of SCs. However, this compound is labile and readily oxidized, resulting in cellular toxicity and preventing its reliable application in this context. We found that a VitC derivative, ascorbic acid 2-glucoside (AA2G), stably maintains the naive pluripotency of murine embryonic SCs (mESCs) and the primitiveness of human mesenchymal SCs (hMSCs) without cellular toxicity. Results: The beneficial effects of AA2G and related molecular mechanisms were evaluated in mESCs, induced pluripotent-SCs (iPSCs), and hMSCs. AA2G was stable in aqueous solution and barely induced cellular toxicity in cultured SCs, unlike VitC. AA2G supplementation recapitulated the well-known effects of VitC, including induction of ten-eleven translocation-dependent DNA demethylation in mESCs and suppression of p53 during generation of murine iPSCs. Furthermore, supplementation of hMSCs with AA2G improved therapeutic outcomes in an asthma mouse model by promoting their self-renewal, engraftment, and anti-inflammatory properties. Particularly, activation of the cAMP-responsive element-binding protein-1 (CREB1) pathway contributed to the ability of AA2G to maintain naive pluripotency of mESCs and functionality of hMSCs. Innovation and Conclusion: Given its long-lasting effects and low cellular toxicity, AA2G supplementation is useful to support the naive pluripotency of mESCs and the primitiveness of hMSCs, affecting their developmental potency and therapeutic efficacy. Furthermore, we demonstrate the significance of the CREB1 pathway in the mechanism of action of AA2G.

Comparative study of rosemary extracts and several synthetic and natural food antioxidants. Relevance of carnosic acid/carnosol ratio.

The antiradical power, at equal concentrations of active principles, of the following antioxidants were studied using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) assay: butylated-hydroxyanisole, butylated-hydroxytoluene, tert-butylhydroquinone, ascorbyl palmitate, tocopherol, grape seed extract, olive extract and five rosemary extracts with different concentrations of carnosic acid (CA) and carnosol (COL). The reaction kinetics of DPPH scavenging activity in each studied substance identified significant variations in the time needed to reach the steady state. Rosemary extracts were seen to be more effective than the other compounds. CA had higher antioxidant activity than COL, although COL seemed to react faster with DPPH. The relevance of the CA/COL ratio for the antioxidant activity of rosemary extracts was also analysed. The presence of COL in rosemary extracts increased the antioxidant activity with an optimal CA/COL ratio of 2.5-3.0. Olive extract and grape seed extract seem to be very promising additives for use as technological antioxidants.

Fabrication and characterization of hyaluronic acid microneedles to enhance delivery of magnesium ascorbyl phosphate into skin.

This study investigated the in vitro transdermal delivery of magnesium ascorbyl phosphate (MAP) through porcine ear skin treated with hyaluronic acid (HA) microneedles (MNs). In this study, the micro-molding method was used to fabricate HA MNs. HA solution (10% w/v) containing 3% of MAP was placed onto a poly(dimethyl siloxane) mold to fill the microchannels under vacuum followed by drying in a desiccator. Scanning electron microscopy was performed to record the dimensions of the MNs. Skin microporation was demonstrated by dye binding. Histological skin sections revealed the shape of microchannels under hematoxylin-eosin staining. The actual depth of the microchannels and drug distribution pathways were studied by confocal microscopy. In vitro permeation on Franz diffusion cells were performed to determine the rate and extent of drug delivery into and across the skin. SEM captured individual MNs from the array, and the length of each MN was found to be ~400 µm. The 10 × 10 MN array prepared, resulted in the formation of 95 to 100 microchannels after 2 mins of treatment. In addition, the histological evaluations showed the formation of microchannels in the skin, complementary in shape to the MNs. The depths of the formed microchannels amounted to ~125 µm as determined by confocal microscopy. The application of the current MN technology enhanced the delivery of MAP into skin (96.8 ± 3.9 µg/cm2) compared to the passive delivery strategy of MAP (44.9 ± 16.3 µg/cm2). HA MNs markedly enhanced the in vitro transdermal delivery of MAP into and across skin.

Ascorbic Acid Derivatives as Potential Substitutes for Ascorbic Acid To Reduce Color Degradation of Drinks Containing Ascorbic Acid and Anthocyanins from Natural Extracts.

Ascorbic acid is widely used in the food industry as a source of vitamin C or as antioxidant. However, it degrades quickly in beverages at acidic pH and can accelerate the degradation of anthocyanins, natural dyes used in beverages, leading to a loss of color. In this work, we investigated the possibility to replace ascorbic acid by ascorbic acid derivatives to prevent its degradation effect on anthocyanins from natural extracts (black carrot, grape juice, and purple sweet potato). For this, the thermal and photolytic stabilities under air and under N2 of ascorbic acid (as reference) and of some ascorbic acid derivatives (3-O-ethyl-l-ascorbic acid, 2-O-α-d-glucopyranosyl-l-ascorbic acid, l-ascorbic acid 2-phosphate sesquimagnesium salt hydrate, l-ascorbyl 2,6-dibutyrate, glyceryl ascorbate, (+)-5,6-O-isopropylidene-l-ascorbic acid), soluble in aqueous model beverages, were studied alone and in the presence of anthocyanins from the natural extracts in citrate buffer at pH 3. The stability was followed by UV-visible spectrometry. To extend the investigation, some properties of the ascorbic acid derivatives (pKa, oxidation potential, bond dissociation energy, ionization potential) were also determined. Moreover, the addition of chlorogenic acid was examined to further stabilize the mixture of anthocyanins with 2-O-α-d-glucopyranosyl-l-ascorbic acid, a promising ascorbic acid derivative.

Lipomatrix: A Novel Ascorbyl Palmitate-Based Lipid Matrix to Enhancing Enteric Absorption of Serenoa Repens Oil.

The class of lipophilic compounds coming from vegetal source represents a perspective in the adjuvant treatment of several human diseases, despite their poor bioavailability in humans. These compounds are generally soluble in fats and poorly soluble in water. The major reason for the poor bioavailability of lipophilic natural compounds after oral uptake in humans is related to their reduced solubility in enteric water-based fluids, leading to an ineffective contact with absorbing epithelium. The main goal to ensure efficacy of such compounds is then creating technological conditions to deliver them into the first enteric tract as hydro-dispersible forms to maximize epithelial absorption. The present work describes and characterizes a new technological matrix (Lipomatrix, Labomar Research, Istrana, TV, Italy) based on a molten fats core in which Ascorbyl Palmitate is embedded, able to deliver lipophilic compounds in a well-dispersed and emulsified form once exposed to duodenal fluids. Authors describe and quantify Lipomatrix delivery of Serenoa repens oil through an innovative in vitro model of human gastro-enteric digestion, reporting results of its improved bioaccessibility, enteric absorption and efficacy compared with not formulated Serenoa repens oil-containing commercial products using in vitro models of human intestine and prostatic tissue.

In vitro characterization of physico-chemical properties, cytotoxicity, bioactivity of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate nasal powder formulation.

An innovative lyophilized dry powder formulation consisting of urea-crosslinked hyaluronic acid (HA-CL) and sodium ascorbyl phosphate (SAP) - LYO HA-CL - SAP- was prepared and characterized in vitro for physico-chemical and biological properties. The aim was to understand if LYO HA-CL - SAP could be used as adjuvant treatment for nasal inflammatory diseases. LYO HA-CL - SAP was suitable for nasal delivery and showed to be not toxic on human nasal septum carcinoma-derived cells (RPMI 2650 cells) at the investigated concentrations. It displayed porous, polygonal particles with unimodal, narrow size distribution, mean geometric diameter of 328.3 ±â€¯27.5 µm, that is appropriate for nasal deposition with no respirable fraction and 88.7% of particles with aerodynamic diameter >14.1 µm. Additionally, the formulation showed wound healing ability on RPMI 2650 cells, and reduced interleukin-8 (IL-8) level in primary nasal epithelial cells pre-induced with lipopolysaccharide (LPS). Transport study across RPMI 2650 cells showed that HA-CL could act not only as carrier for SAP and active ingredient itself, but potentially also as mucoadhesive agent. In conclusion, these results suggest that HA-CL and SAP had anti-inflammatory activity and acted in combination to accelerate wound healing. Therefore, LYO HA-CL - SAP could be a potential adjuvant in nasal anti-inflammatory formulations.

Thymol, alpha tocopherol, and ascorbyl palmitate supplementation as growth enhancers for broiler chickens.

Consumer concern on the quality of products and animal welfare has greatly increased during the past decades. Dietary synthetic antibiotic products used as growth promoters have been restricted or banned in many countries. Edible plants, essential oils, or their main components were suggested as natural feed supplements to improve growth, products' quality, and welfare-related parameters. Thymol (THY), a main component of oregano essential oil, has been proved as an effective antimicrobial and antioxidant compound. Tocopherol (TOC) evidenced antioxidant activity with potential as a growth promoter and a synergic antioxidant activity between TOC and ascorbyl palmitate (AP) has also been reported. Herein, we evaluated whether broiler diet supplementation with THY, and THY with a formulation mix containing TOC and AP (1:0.5:0.5, respectively) have potential as growth enhancers under commercial conditions. Potential protective effects against foot pad dermatitis and hock burns were also evaluated. Newly hatched male broiler chicks with similar body weight (BW) were randomly assigned to 1 of 7 groups (4 replicates each) as follows: Basal (no feed supplements added), Promotor (Basal + 6.26 µmol flavomycin/kg feed), BHT (Basal + 1.33 mmol of buthylated hidroxytoluene (BHT)/kg feed), Prom-BHT (Basal + 6.26 µmol flavomycin/kg feed + 1.33 mmol of BHT/kg feed), TOC-AP (Basal + 0.67 mmoles of TOC + 0.67 mmoles of AP/kg feed), THY (Basal + 1.33 mmoles of THY/kg feed), and THY-TOC-AP (Basal + 0.67 mmoles of THY + 0.67 mmoles of a mix 1:1 of TOC-AP). Along 7 wk, BW, feed intake, and feed conversion ratio were evaluated. Skin injuries were assessed at 35 d of age. At the end of the study (42 d), compared to Basal group, similarly enhanced final BW were observed in all groups but TOC-AP. No main differences between groups were detected in feed intake, feed conversion ratio, or skin injuries. Findings suggest that THY itself or in combination with TOC-AP may have value as a natural growth enhancer alternative for broilers.

Ascorbic acid derivative DDH-1 ameliorates psoriasis-like skin lesions in mice by suppressing inflammatory cytokine expression.

Psoriasis is a chronic inflammatory skin disease in which inflammatory cytokines play a major role in its pathogenesis. Because DDH-1, a novel amphipathic ascorbic acid derivative, has been recently shown to reduce inflammatory cytokine expression in human keratinocytes in vitro, we investigated its effect on imiquimod-induced psoriasis-like skin lesions in C57BL/6 mice. We first found that IL-1ß and TNF-α mRNA expression was significantly decreased in the skin lesions treated with DDH-1. Furthermore, cutaneous administration of DDH-1 ameliorated psoriasis-like skin lesions. These results suggest that DDH-1 may be effective in the prevention and supplemental treatment of psoriasis.

Potential Antitumor Activity of 2-O-α-d-Glucopyranosyl-6-O-(2-Pentylheptanoyl)-l-Ascorbic Acid.

Intravenous administration of high-dose ascorbic acid (AA) has been reported as a treatment for cancer patients. However, cancer patients with renal failure cannot receive this therapy because high-dose AA infusion can have side effects. To solve this problem, we evaluated the antitumor activity of a lipophilic stable AA derivative, 2-O-α-d-glucopyranosyl-6-O-(2-pentylheptanoyl)-l-ascorbic acid (6-bOcta-AA-2G). Intravenous administration of 6-bOcta-AA-2G suppressed tumor growth in colon-26 tumor-bearing mice more strongly than did AA, even at 1/10 of the molar amount of AA. Experiments on the biodistribution and clearance of 6-bOcta-AA-2G and its metabolites in tumor-bearing mice showed that 6-bOcta-AA-2G was hydrolyzed to 6-O-(2-propylpentanoyl)-l-ascorbic acid (6-bOcta-AA) slowly to yield AA, and the results suggested that this characteristic metabolic pattern is responsible for making the antitumor activity of 6-bOcta-AA-2G stronger than that of AA and that the active form of 6-bOcta-AA-2G showing antitumor activity is 6-bOcta-AA. In in vitro experiments, the oxidized form of 6-bOcta-AA as well as 6-bOcta-AA showed significant cytotoxicity, while the oxidized forms of ascorbic acid showed no cytotoxicity at all, suggesting that the antitumor activity mechanism of 6-bOcta-AA-2G is different from that of AA and that the antitumor activity is due to the reduced and oxidized form of 6-bOcta-AA. The findings suggest that 6-bOcta-AA-2G is a potent candidate as an alternative drug to intravenous high-dose AA.

Vitamin C promotes oligodendrocytes generation and remyelination.

Oligodendrocyte-formed myelin sheaths play important roles in the neuronal functions in the central nervous system. In demyelinating diseases, such as Multiple Sclerosis, the myelin sheaths are damaged and the remyelinating process is somehow hindered. Restoration of the myelin sheaths requires the differentiation of the oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). To discover small molecule compounds that might promote the OPC to OL differentiation, a high-throughput screening system is established and L-ascorbyl-2-phosphate (As-2P), a stable form of Vitamin C (Vc), is found to greatly enhance the OPC to OL differentiation. As-2P promotes gradual expression of OL lineage markers, including O4, CNPase and MBP, in a dose- and time-dependent manner. It also facilitates the formation of myelin sheaths in OPC-neuron co-culture. As-2P also promotes the repair of the myelin sheaths in vivo and provides significant therapeutic effect in a cuprizone-mediated demyelination animal model. Interestingly, As-2P's function in promoting OPC differentiation is not related to its antioxidant activity. And an intracellular rather than an extracellular mechanism might be involved. Considering the safe use of Vc as a dietary supplement for many years, it might also be used as an alternative medicine for CNS demyelinating diseases.

Deep insemination with sex-sorted Cashmere goat sperm processed in the presence of antioxidants.

Flow cytometrically sex-sorted sperm have been widely used for improving reproductive management in the dairy industry. However, the industrial application of this technology in other domestic species is largely limited by the lower fertility after insemination. The aim of this study was to investigate effects of antioxidant supplementation during the sex-sorting and freezing process on the quality and functions of sorted sperm from Liaoning Cashmere goats. We tested the effects of antioxidant supplementation during sex-sorting and freezing process, including ascorbic acid-2-glucoside AA-2G, glutathione, melatonin and vitamin C (VC), on the quality and functions of sex-sorted fresh and frozen-thawed sperm. Based on these experiments, we performed deep insemination with sex-sorted sperm using our improved strategy, in comparison to unsorted sperm. In Experiment 1, compared with control group and other antioxidants, AA-2G supplementation significantly alleviated the degradation of motility and viability of fresh sperm after sorting and showed the highest percentage of sperm with normal morphology. In addition, AA-2G supplementation showed an evident protection against the sorting process-induced membrane and acrosome damage. In Experiment 2, AA-2G supplementation was most effective in protecting motility, while melatonin supplementation appears to facilitate the degradation of quality of frozen-thawed sex-sorted sperm. In Experiment 3, we performed deep insemination with sperm that were sorted and frozen in the presence of AA-2G and obtained a satisfying pregnancy rate comparable to that from unsorted sperm. The results showed that AA-2G supplementation efficiently protects quality and function of both fresh and frozen-thawed sex-sorted sperm of Cashmere goats, thus obtaining a satisfying pregnancy outcome.