Interaction of Bioactive Compounds of Moringa oleifera Leaves with SARS-CoV-2 Proteins to Combat COVID-19 Pathogenesis: a Phytochemical and In Silico Analysis.

Novel SARS-CoV-2 claimed a large number of human lives. The main proteins for viral entry into host cells are SARS-CoV-2 spike glycoprotein (PDB ID: 6VYB) and spike receptor-binding domain bound with ACE2 (spike RBD-ACE2; PDB ID: 6M0J). Currently, specific therapies are lacking globally. This study was designed to investigate the bioactive components from Moringa oleifera leaf (MOL) extract by gas chromatography-mass spectroscopy (GC-MS) and their binding interactions with spike glycoprotein and spike RBD-ACE2 protein through computational analysis. GC-MS-based analysis unveiled the presence of thirty-seven bioactive components in MOL extract, viz. polyphenols, fatty acids, terpenes/triterpenes, phytosterols/steroids, and aliphatic hydrocarbons. These bioactive phytoconstituents showed potential binding with SARS-CoV-2 spike glycoprotein and spike RBD-ACE2 protein through the AutoDock 4.2 tool. Further by using AutoDock 4.2 and AutoDock Vina, the top sixteen hits (binding energy ≥ - 6.0 kcal/mol) were selected, and these might be considered as active biomolecules. Moreover, molecular dynamics simulation was determined by the Desmond module. Interestingly two biomolecules, namely ß-tocopherol with spike glycoprotein and ß-sitosterol with spike RBD-ACE2, displayed the best interacting complexes and low deviations during 100-ns simulation, implying their strong stability and compactness. Remarkably, both ß-tocopherol and ß-sitosterol also showed the drug- likeness with no predicted toxicity. In conclusion, these findings suggested that both compounds ß-tocopherol and ß-sitosterol may be developed as anti-SARS-CoV-2 drugs. The current findings of in silico approach need to be optimized using in vitro and clinical studies to prove the effectiveness of phytomolecules against SARS-CoV-2.

Deep eutectic solvent-based liquid-phase microextraction coupled with reversed-phase high-performance liquid chromatography for determination of α-, ß-, γ-, and δ-tocopherol in edible oils.

For simultaneous analysis of four fat-soluble tocopherols (α-, ß-, γ-, and δ-) in edible oils, an efficient and green method using deep eutectic solvent-based liquid-phase microextraction (DES-LPME) coupled with reversed-phase high-performance liquid chromatography (RP-HPLC) was developed. The DESs formed by different quaternary ammonium salts and ethanol were used as the extractants. Tetrabutylammonium chloride (TBAC)-ethanol DES at a molar ratio of 1:2 achieved the best extraction efficiency. Under the optimized conditions, the detection limits were in the range of 2.1-3.0 ng mL-1. The intra-day and inter-day repeatability were in the ranges of 3.9-5.3% and 4.8-7.1%, respectively, and the recoveries for the real samples varied from 80.7% to 105.4%. The developed method was successfully employed for the determination of all four tocopherol homologues with an RP-HPLC system containing a COSMOSIL π-NAP column in five edible oils collected locally. Graphical abstract.

Performance of antioxidative compounds under frying conditions: A review.

Although much study has been done assessing activity of antioxidants at ambient and accelerated storage temperatures, the results cannot correctly depict their performance under frying conditions. Due to the stringent conditions imposed, most conventional antioxidative compounds failed under frying conditions, suggesting the need for a continuous modification to improve their effectiveness. Although syntheses and performance evaluation of over a hundred (semi)synthetic antioxidants have been reported in literature, only a small fraction have been specifically designed and/or evaluated under frying conditions. Here, the performance under frying conditions of major natural and synthetic antioxidants is reviewed. The recent trend in the designing of antioxidants for frying applications is also reviewed with the view of stimulating further study in this direction.

Involvement of metabolites in early defense mechanism of oil palm (Elaeis guineensis Jacq.) against Ganoderma disease.

Understanding the mechanism of interaction between the oil palm and its key pathogen, Ganoderma spp. is crucial as the disease caused by this fungal pathogen leads to a major loss of revenue in leading palm oil producing countries in Southeast Asia. Here in this study, we assess the morphological and biochemical changes in Ganoderma disease infected oil palm seedling roots in both resistant and susceptible progenies. Rubber woodblocks fully colonized by G. boninense were applied as a source of inoculum to artificially infect the roots of resistant and susceptible oil palm progenies. Gas chromatography-mass spectrometry was used to measure an array of plant metabolites in 100 resistant and susceptible oil palm seedling roots treated with pathogenic Ganoderma boninense fungus. Statistical effects, univariate and multivariate analyses were used to identify key-Ganoderma disease associated metabolic agitations in both resistant and susceptible oil palm root tissues. Ganoderma disease related defense shifts were characterized based on (i) increased antifungal activity in crude extracts, (ii) increased lipid levels, beta- and gamma-sitosterol particularly in the resistant progeny, (iii) detection of heterocyclic aromatic organic compounds, benzo [h] quinoline, pyridine, pyrimidine (iv) elevation in antioxidants, alpha- and beta-tocopherol (iv) degraded cortical cell wall layers, possibly resulting from fungal hydrolytic enzyme activity needed for initial penetration. The present study suggested that plant metabolites mainly lipids and heterocyclic aromatic organic metabolites could be potentially involved in early oil palm defense mechanism against G. boninense infection, which may also highlight biomarkers for disease detection, treatment, development of resistant variety and monitoring.

Some rape/canola seed oils: fatty acid composition and tocopherols.

Seed samples of some rape and canola cultivars were analysed for oil content, fatty acid and tocopherol profiles. Gas liquid chromotography and high performance liquid chromotography were used for fatty acid and tocopherol analysis, respectively. The oil contents of rape and canola seeds varied between 30.6% and 48.3% of the dry weight (p<0.05). The oil contents of rapeseeds were found to be high compared with canola seed oils. The main fatty acids in the oils are oleic (56.80-64.92%), linoleic (17.11-20.92%) and palmitic (4.18-5.01%) acids. A few types of tocopherols were found in rape and canola oils in various amounts: α-tocopherol, γ-tocopherol, δ-tocopherol, ß-tocopherol and α-tocotrienol. The major tocopherol in the seed oils of rape and canola cultivars were α-tocopherol (13.22-40.01%) and γ-tocopherol (33.64-51.53%) accompanied by α-T3 (0.0-1.34%) and δ-tocopherol (0.25-1.86%) (p<0.05). As a result, the present study shows that oil, fatty acid and tocopherol contents differ significantly among the cultivars.

Circulating Alpha-Tocopherol and Insulin Sensitivity Among Older Men With Chronic Kidney Disease.

OBJECTIVE: Insulin resistance is common in individuals with chronic kidney disease (CKD) and may be partly explained by modifiable risk factors. In the general population, vitamin E supplementation has been suggested to improve both insulin sensitivity and secretion. We here explore the potential role of vitamin E as a modifiable risk factor for insulin resistance among individuals with CKD. DESIGN: Observational study. SETTING: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate < 60 mL/minute/1.73 m(2) or urinary albumin excretion rate ≥ 20 mg/minute from the third examination cycle of Uppsala Longitudinal Study of Adult Men. SUBJECTS: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate < 60 mL/minute/1.73 m(2) or urinary albumin excretion rate ≥ 20 µg/minute. METHODS: Serum α-, ß-, and γ-tocopherol concentrations were measured by high-performance liquid chromatography and expressed as µmol/total serum cholesterol and triglycerides (in mmol). Dietary vitamin E intake was estimated from 7-day food records. MAIN OUTCOME MEASURE: Insulin sensitivity index (M/I ratio) was measured by hyperinsulinemic-euglycemic glucose clamps. Univariate and multivariate regression models were fitted to assess the association between M/I and circulating concentrations of tocopherols. RESULTS: The mean serum concentration of α-, ß-, and γ- was 37.4 ± 6.58, 0.89 ± 0.23, and 4.32 ± 1.69 µmol/mmol, respectively. Median dietary vitamin E intake was 6.14 (interquartile range, 5.48-6.82) mg/day. In crude and fully-adjusted multivariate regression analyses, serum α-tocopherol levels were directly and strongly associated with M/I (standard ß = 0.17, P = .003). No such association was observed for dietary vitamin E, serum ß-, and γ-tocopherol concentrations. CONCLUSIONS: Serum α-tocopherol concentration associates with insulin sensitivity in nondiabetic older men with CKD.

Subcritical extraction of flaxseed oil with n-propane: Composition and purity.

Flaxseed (Linum usitatissimum L.) oil was obtained via subcritical n-propane fluid extraction (SubFE) under different temperatures and pressures with an average yield of 28% and its composition, purity and oxidative stability were compared to oils obtained via conventional solvent extraction methods (SEMs). When the oxidative stability was measured by differential scanning calorimetry, the oil was found to be up to 5 times more resistant to lipid oxidation as compared to the SEM oils. Direct infusion electrospray ionization mass spectrometry (ESI-MS) analysis showed characteristic and similar TAG profiles for SubFE and SEMs oils but higher purity for the SubFE oil. The flaxseed oil content of ß-tocopherol, campesterol, stigmasterol and sitosterol were quantified via GC-MS. SubFE showed to be a promising alternative to conventional SEM since SubFE provides an oil with higher purity and higher oxidation stability and with comparable levels of biologically active components.

Temperature dependence of autoxidation of perilla oil and tocopherol degradation.

Temperature dependence of the autoxidation of perilla oil and tocopherol degradation was studied with corn oil as a reference. The oils were oxidized in the dark at 20, 40, 60, and 80 degrees C. Oil oxidation was determined by peroxide and conjugated dienoic acid values. Tocopherols in the oils were quantified by HPLC. The oxidation of both oils increased with oxidation time and temperature. Induction periods for oil autoxidation decreased with temperature, and were longer in corn oil than in perilla oil, indicating higher sensitivity of perilla oil to oxidation. However, time lag for tocopherol degradation was longer in perilla oil, indicating higher stability of tocopherols in perilla oil than in corn oil. Activation energies for oil autoxidation and tocopherol degradation were higher in perilla oil (23.9 to 24.2, 9.8 kcal/mol, respectively) than in corn oil (12.5 to 15.8, 8.8 kcal/mol, respectively) indicating higher temperature-dependence in perilla oil. Higher stability of tocopherols in perilla oil was highly related with polyphenols. The study suggests that more careful temperature control is required to decrease the autoxidation of perilla oil than that of corn oil, and polyphenols contributed to the oxidative stability of perilla oil by protecting tocopherols from degradation, especially at the early stage of oil autoxidation.

Characterization of a potential nutraceutical ingredient: pomegranate (Punica granatum L.) seed oil unsaponifiable fraction.

The chemical fingerprinting of the unsaponifiable fraction of different Punica granatum seed oils was performed in order to evaluate their potential as a functional food ingredient. Qualitative and quantitative determinations of tocopherol, aliphatic alcohol (including policosanol), squalene, phytosterols and triterpene contents were performed by GC-MS. A high yield (3.1-4.2%) of unsaponifiable matter was obtained and consistent levels of squalene (up to 800 mg/kg) and policosanol (118-185 mg/kg) were noticed. ß-sitosterol (up to 8069 mg/kg) and cycloartenol (5916-7766 mg/kg) were predominant in phytosterol and triterpene fractions, while ß- and δ-tocopherol were the most abundant vitamin E forms. Some minor variations were noticed between samples. From the results obtained, it can be suggested that the seed oil of P. granatum can be considered an interesting alimentary source of substances of nutraceutical value involved in the modulation of cholesterol metabolism.

The comparison of black currant juice and vitamin E for the prevention of oxidative stress.

Black currant is known as a fruit with a very strong in vitro antioxidative capacity, but its in vivo antioxidant efficacy has not yet been characterized. The aim of the experiment was to determine the potency of black currant juice in comparison to vitamin E, for decreasing oxidative stress. Oxidative stress was induced by high intake of polyunsaturated fatty acids (PUFAs) in pigs as a model for humans. Twenty-four growing pigs were divided into four groups. All groups received isocaloric daily rations composed of an equal amount of basal diet that was supplemented with starch (CONT), linseed oil (OIL), linseed oil and black currant juice (OIL+BCJ), or linseed oil and vitamin E (OIL+VIT E). The experiment confirmed that the high proportion of PUFAs in the OIL group increased oxidative stress. In comparison with the OIL group, vitamin E supplementation significantly lowered plasma malondiadehyde (MDA) and the 24-hour urine MDA excretion rate, and reduced the degree of DNA damage in leukocytes to the level of the CONT group. The black currant juice intake failed to significantly decrease plasma MDA and 24-hour urine MDA excretion rate, but did reduce the degree of DNA damage in leukocytes to the level of the CONT group, as well as increase plasma beta+gamma-tocopherol concentrations. Although black currant juice did not reduce the formation of MDA, it efficiently prevented DNA damage induced by the high intake of PUFAs. It could be concluded that under these experimental conditions vitamin E was more efficient as an antioxidant that black currant juice.

Implications for degenerative disorders: antioxidative activity, total phenols, flavonoids, ascorbic acid, beta-carotene and beta-tocopherol in Aloe vera.

In order to demonstrate whether the known biological effects of Aloe vera (L.) Burm. fil. could correlate with the antioxidant activity of the plant, the antioxidant activity of the aqueous leaf extract was investigated. The present study demonstrated that the aqueous extract from A. vera leaves contained naturally occuring antioxidant components, including total phenols, flavonoids, ascorbic acid, beta-carotene and alpha-tocopherol. The extract exhibited inhibitory capacity against Fe(3+)/ascorbic acid induced phosphatidylcholine liposome oxidation, scavenged stable DPPH(*), ABTS(*+) and superoxide anion radicals, and acted as reductant. In contrast, the leaf inner gel did not show any antioxidant activity. It was concluded that the known beneficial effects of Aloe vera could be attributed to its antioxidant activity and could be related to the presence of phenolic compounds and antioxidant vitamins.

Distribution of alpha-, gamma (+beta)- and delta-tocopherol in the seminal plasma, spermatozoa and seminal vesicles of rabbit.

Dietary vitamin E supplementation plays a key role in animal reproduction by protecting germ cells from oxidative damage. Recently, alpha-tocopherol homologues (namely, beta-, gamma- and delta-tocopherol) have been the object of increasing research because of their peculiar nonantioxidant properties. We found that these tocol-derived compounds are not homogeneously distributed among semen components. Alpha-T was the major vitamin E homologue found in all semen fractions. Half of the total gamma (+beta)-T was found in germ cells, while more than 50% of total delta-T was preferentially accumulated in seminal plasma. The concentration of various tocol-derived compounds depended on their relative amounts in diet and the competition for saturable enzymes implicated in their metabolism. A higher concentration of delta-T in seminal plasma may be related to its more polar nature. However, the biological function of this compound in semen remains to be cleared. To our knowledge, this is the first study aimed at identifying alpha-tocopherol homologues in rabbit semen fractions.

Dietary alpha-, beta-, gamma- and delta-tocopherols in lung cancer risk.

Studies of vitamin E and cancer have focused on the alpha-tocopherol form of the vitamin. However, other forms of vitamin E, in particular gamma-tocopherol may have unique mechanistic characteristics relevant to lung cancer prevention. In an ongoing study of 1,088 incident lung cancer cases and 1,414 healthy matched controls, we studied the associations between 4 tocopherols (alpha-, beta-, gamma-, and delta-tocopherol) in the diet and lung cancer risk. Using multiple logistic regression analysis, the adjusted odds ratios (OR) and 95% confidence intervals (CI) of lung cancer for increasing quartiles of dietary alpha-tocopherol intake were 1.0, 0.63 (0.50-0.79), 0.58 (0.44-0.76) and 0.39 (0.28-0.53), respectively (p-trend < 0.0001). For dietary intake of beta-tocopherol, the OR and 95% CI for all subjects were: 1.0, 0.79 (0.63-0.98), 0.59 (0.45-0.78) and 0.56 (0.42-0.74), respectively (p-trend < 0.0001). Similar results for dietary gamma-tocopherol intake were observed: 1.0, 0.84 (0.67-1.06), 0.76 (0.59-0.97) and 0.56 (0.42-0.75), respectively (p- trend = 0.0002). No significant association between delta-tocopherol intake and lung cancer risk was detected. When the 4 tocopherols were summed as total tocopherol intake, a monotonic risk reduction was also observed. When we entered the other tocopherols in our model, only the association with dietary alpha-tocopherol intake remained significant; i.e., increasing intake of dietary alpha-tocopherol accounted for 34-53% reductions in lung cancer risk. To the best of our knowledge, this is the first report of the independent associations of the 4 forms of dietary tocopherol (alpha-, beta-, gamma- and delta-tocohperol) on lung cancer risk. Given the limitations with case-control studies, these findings need to be confirmed in further investigations.

Tocopherols enhance neurogenesis in dentate gyrus of adult rats.

In the dentate gyrus of the mammalian hippocampus, neurogenesis carries on throughout postnatal life. The aim of this work was to identify an exogenous control factor of adult neurogenesis. Neurogenesis in the adult dentate gyrus was previously found to be enhanced in vitamin E-deficient rats. The effects of alpha- or beta-tocopherol supplementation on neurogenesis in the adult dentate gyrus were investigated by 5-bromo-2'-deoxyuridine labeling. Tocopherol was found to increase the survival of newborn cells and the total number of granule cells in the adult rat dentate gyrus. Newborn cells were phenotypically characterized by expression of the immature neuron marker TOAD-64 (turned on after division-64). Therefore tocopherol in high doses possibly increases the number of granule cells in the dentate gyrus by saving newborn cells from death.