In vitro antiaging evaluation of sunscreen formulated from nanostructured lipid carrier and tocotrienol-rich fraction

Chee Chin Chu, Zafarizal Aldrin Bin Azizul Hasan, Chin Ping Tan, Kar Lin Nyam

J Pharm Sci . 2021 Aug 20;S0022-3549(21)00423-8. doi: 10.1016/j.xphs.2021.08.020.

Abstract

Chronic exposure to ultraviolet (UV) radiation leads to photoaging. There is a tremendous rise in products having a dual activity of photoprotection and antiaging. In vitro analysis in dermal fibroblasts and their biological mechanisms involved are critical to determine antiaging potential. The study aimed to investigate the antiaging potential of sunscreen formulated from nanostructured lipid carrier and tocotrienol-rich fraction (NLC-TRF sunscreen). The antioxidant activity of the NLC-TRF sunscreen was evaluated by radical scavenging and hydrogen peroxide inhibition properties. Also, collagenase, elastase and matrix metalloproteinase-1 (MMP-1) inhibition activities, and type I collagen and elastin protein expression were studied. Quantitative real-time polymerase chain reaction (qPCR) was used to evaluate the mRNA expression of fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), type I collagen (COL1A1), elastin (ELN), MMP-1, MMP-2, and tissue inhibitor matrix metalloproteinase-1 (TIMP-1). The results suggested that NLC-TRF sunscreen is effective in radical, anti-hydrogen peroxide, and collagenase, elastase and MMP-1 inhibition activities. Besides, a significant increase for type I collagen (3.47-fold) and elastin (2.16-fold) protein and fibroblast regeneration genes (FGF (2.12-fold), VEGF (1.91-fold), TGF-β1 (2.84-fold), TIMP-1 (1.42-fold), ELN (2.13-fold)) were observed after sample treatment. These findings support the therapeutic potential of NLC-TRF sunscreen in antiaging.

Maria Ester La Torre, Ines Villano, Marcellino Monda, Antonietta Messina, Giuseppe Cibelli, Anna Valenzano, Daniela Pisanelli, Maria Antonietta Panaro, Nicola Tartaglia, Antonio Ambrosi, Marco Carotenuto, Vincenzo Monda, Giovanni Messina, Chiara Porro

Brain Sci . 2021 Aug 20;11(8):1098. doi: 10.3390/brainsci11081098.

Abstract

Microglia are the first line of defense at the level of the central nervous system (CNS). Phenotypic change in microglia can be regulated by various factors, including the orexin system. Neuroinflammation is an inflammatory process mediated by cytokines, by the lack of interaction of specific receptors such as the OX2-OX2R complex, caused by systemic tissue damage or, more often, associated with direct damage to the CNS. Chronic activation of microglia could lead to long-term neurodegenerative diseases. This review aims to explore how tocopherol (vitamin E) and the orexin system may play a role in the prevention and treatment of microglia inflammation and, consequently, in neurodegenerative diseases thanks to its antioxidant properties. The results of animal and in vitro studies provide evidence to support the use of tocopherol for a reduction in microglia inflammation as well as a greater activation of the orexinergic system. Although there is much in vivo and in vitro evidence of vitamin E antioxidant and protective abilities, there are still conflicting results for its use as a treatment for neurodegenerative diseases that speculate that vitamin E, under certain conditions or genetic predispositions, can be pro-oxidant and harmful.

Parichehr Behfarnia, Mina Dadmehr, Seyedeh Negin Hosseini, Seyed Amir Mirghaderi

Dent Res J (Isfahan) . 2021 Aug 18;18:62. eCollection 2021.

Abstract

Background: The purpose of this study was to evaluate the effect of Vitamin E supplements on chronic periodontitis based on the clinical parameters of pocket depth and clinical attachment level and total antioxidant capacity (TAC) of saliva.

Materials and methods: In this clinical trial, 16 patients with chronic periodontitis were selected and divided into two groups. The indices of pocket depth and attachment loss for 6 teeth per person were measured with a periodontal probe. A total of 41 teeth in the control group and 42 teeth in the case group were examined. Then, 2 ml nonstimulated saliva was collected from each patient. All patients were treated with scaling and root planing (SRP). The case group consumed 200 IU supplementary Vitamin E daily for up to 2 months. After 2 months, clinical indices were re-measured and 2 ml nonstimulated saliva was collected. The TAC of saliva samples was measured by using Zellbio’s TAC Kit. Data were analyzed by the SPSS software and were evaluated in each group between the first session and 2 months later with paired t-test. The differences between the two groups were evaluated through the independent t-test (α ≤ 0.05).

Results: Independent t-test showed that mean change in TAC (P = 0.14) and pocket depth changes (P = 0.33) was not significant between two groups 2 months after SRP, but mean attachment loss changes in the case group was significantly less than the control group (P = 0.03).

Conclusion: The results of this study indicate that Vitamin E supplementation with SRP can reduce the inflammatory process of periodontitis and improve periodontal clinical indices and decrease the amount of attachment loss.

Abolfathi Mohammad, Ebrahim Falahi, Mohd Yusof Barakatun-Nisak, Zubaidah Nor Hanipah, S Mohd Redzwan, Loqman Mohamad Yusof, Mohsen Gheitasvand, Farahnaz Rezaie

Diabetes Metab Syndr . Jul-Aug 2021;15(4):102158. doi: 10.1016/j.dsx.2021.05.031. Epub 2021 May 31.

Abstract

Background and aims: The studies have shown that α-tocopherol supplementation could improve lipid profile in diabetes mellitus (DM) patients. Nonetheless, the result remains inconsistent. Therefore, this meta-analysis was performed to evaluate the efficacy of α-tocopherol supplement on lipid parameters in DM patients.

Methods: We conducted an extensive search via Cochrane Library, PubMed, Scopus, and Web of Science databases to acquire the reported RCTs up to October 2020.

Results: The results showed no effects of α-tocopherol supplementation on lipid profile in DM patients except when used ≥12 weeks.

Conclusions: α-tocopherol supplementation in DM patients had no significant effect on lipid profiles.

Katalin Koczok, László Horváth, Zeljka Korade, Zoltán András Mezei, Gabriella P Szabó, Ned A Porter, Eszter Kovács, Károly Mirnics, István Balogh

Biomolecules . 2021 Aug 17;11(8):1228. doi: 10.3390/biom11081228.

Abstract

Smith-Lemli-Opitz syndrome (SLOS) is a severe monogenic disorder resulting in low cholesterol and high 7-dehydrocholesterol (7-DHC) levels. 7-DHC-derived oxysterols likely contribute to disease pathophysiology, and thus antioxidant treatment might be beneficial because of high oxidative stress. In a three-year prospective study, we investigated the effects of vitamin E supplementation in six SLOS patients already receiving dietary cholesterol treatment. Plasma vitamin A and E concentrations were determined by the high-performance liquid chromatography (HPLC) method. At baseline, plasma 7-DHC, 8-dehydrocholesterol (8-DHC) and cholesterol levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The clinical effect of the supplementation was assessed by performing structured parental interviews. At baseline, patients were characterized by low or low-normal plasma vitamin E concentrations (7.19-15.68 μmol/L), while vitamin A concentrations were found to be normal or high (1.26-2.68 μmol/L). Vitamin E supplementation resulted in correction or significant elevation of plasma vitamin E concentration in all patients. We observed reduced aggression, self-injury, irritability, hyperactivity, attention deficit, repetitive behavior, sleep disturbance, skin photosensitivity and/or eczema in 3/6 patients, with notable individual variability. Clinical response to therapy was associated with a low baseline 7-DHC + 8-DHC/cholesterol ratio (0.2-0.4). We suggest that determination of vitamin E status is important in SLOS patients. Supplementation of vitamin E should be considered and might be beneficial.

Aneta Wojdyło, Igor Piotr Turkiewicz, Karolina Tkacz, Francisca Hernandez

J Sci Food Agric . 2021 Aug 16. doi: 10.1002/jsfa.11481. Online ahead of print.

Abstract

Background: Nowadays it is highly important to find new, cheap and widely available sources of tocopherol and tocotrienol compounds, and leaves are promising unconventional sources. The main goal of this study was to extend the currently limited knowledge concerning tocopherol and tocotrienol isomers composition determined using ultra-high performance liquid chromatography with fluorescence detection analysis for various fruit tree leaves such as apple, pear, quince, apricot, peach, plum, sour cherry and sweet cherry. The leaves were collected 2 weeks after tree blooming and after fruit collection. Tocopherol and tocotrienol isomers were identified and quantified for the first time in all fruit tree leaves.

Results: The total tocopherol content ranged from 203.34 to 260.86 μg g^-1 dry weight for spring leaves and from 23.83 to 235.62 μg g^-1 dry weight for autumn leaves and consisted mainly of α-tocopherol. The rest of the isomers of tocopherol and tocotrienols were also found, but in trace amounts. A significantly lower content of tocopherols and tocotrienols was detected in leaves after autumn collection of fruits compared to leaves collected after blooming. Among the analyzed leaves, time collected and species were significantly more important than their cultivars. Regarding quantification analysis, apricot > peach > > plums > apples leaves were identified as the best sources of tocopherols, and sweet and sour cherry leaves exhibited a lower content.

Conclusion: Fruit tree leaves are a novel significant source and good material for isolation of α-tocopherol for application in cosmetics, pharmaceuticals or in the food industry – for example, production of beverages or other functional foods.

Oluwatosin O Ojo, David S Leake

Free Radic Res . 2021 Aug 16;1-10. doi: 10.1080/10715762.2021.1964494. Online ahead of print.

Abstract

Low density lipoprotein (LDL) might be oxidized by iron in the lysosomes of macrophages in atherosclerotic lesions. We have shown previously that the iron-storage proteinferritin can oxidize LDL at lysosomal pH. We have now investigated the roles of the most important antioxidant contained in LDL, α-tocopherol (the main form of vitamin E) and of ascorbate (vitamin C), a major water-soluble antioxidant, on LDL oxidation by ferritin at lysosomal pH (pH 4.5). We incubated LDL with ferritin at pH 4.5 and 37 °C and measured its oxidation by monitoring the formation of conjugated dienes at 234 n min a spectrophotometer. α-Tocopherol is well known to inhibit LDL oxidation at pH 7.4, but enrichment of LDL with α-tocopherol was unable to inhibit LDL oxidation by ferritin at pH 4.5. Ascorbate had a complex effect on LDL oxidation by ferritin at lysosomal pH and exhibited both antioxidant and pro-oxidant effects. It had no antioxidant effect on partially oxidized LDL, only a pro-oxidant effect. Ascorbate completely inhibited LDL oxidation by copper at pH 7.4 for a long period, but in marked contrast did not inhibit LDL oxidation by copper at lysosomal pH. Dehydroascorbate, the oxidation product of ascorbate, had a pronounced pro-oxidant effect on LDL incubated with ferritin at pH 4.5. The inability of α-tocopherol and ascorbate to effectively inhibit LDL oxidation by ferritin at lysosomal pH might help to explain why the large clinical trials with these vitamins failed to show protection against cardiovascular diseases.

Shoko Aoki, Kazumasa Yamagishi, Koutatsu Maruyama, Rie Kishida, Ai Ikeda, Mitsumasa Umesawa, Cui Renzhe, Yasuhiko Kubota, Mina Hayama-Terada, Yuji Shimizu, Isao Muraki, Hironori Imano, Tomoko Sankai, Takeo Okada, Akihiko Kitamura, Masahiko Kiyama, Hiroyasu Iso

Sci Rep . 2021 Aug 12;11(1):16429. doi: 10.1038/s41598-021-95671-7.

Abstract

Tocopherols, strong antioxidants, may be useful in preventing dementia, but the epidemiological evidence is insufficient. We performed a community-based follow-up study of Japanese, the Circulatory Risk in Community Study, involving 3739 people aged 40-64 years at baseline (1985-1999). Incident disabling dementia was followed up from 1999 through 2020. For subtype analysis, we classified disabling dementia into that with and that without a history of stroke. Dietary intake of tocopherols (total, α, β, γ, and δ) were estimated using 24-h recall surveys. During a median follow-up of 19.7 years, 670 cases of disabling dementia developed. Total tocopherol intake was inversely associated with risk of disabling dementia with multivariable hazard ratios (95% confidence intervals) of 0.79 (0.63-1.00) for the highest versus lowest quartiles of total tocopherol intake (P for trend = 0.05). However, the association was strengthened when further adjusted for α-linolenic acid intake (Spearman correlation with total tocopherol intake = 0.93), with multivariable hazard ratios of 0.50 (0.34-0.74) (P for trend = 0.001) but was weakened and nonsignificant when further adjusted for linoleic acid intake (Spearman correlation with total tocopherol intake = 0.92), with multivariable hazard ratios of 0.69 (0.47-1.01) (P for trend = 0.05). Similar but nonsignificant inverse associations were observed for α-, γ-, and δ-tocopherols but not for β-tocopherol. These results were similar regardless of the presence of a history of stroke. Dietary tocopherol intake was inversely associated with risk of disabling dementia, but its independent effect was uncertain owing to a high intercorrelation of α-linolenic linoleic acids with total tocopherol intake. Even with such confounding, a diet high in tocopherols may help prevent the onset of dementia.

Konstantin Neukirch, Khaled Alsabil, Chau-Phi Dinh, Rossella Bilancia, Martin Raasch, Alexia Ville, Ida Cerqua, Guillaume Viault, Dimitri Bréard, Simona Pace, Veronika Temml, Elena Brunner, Paul M Jordan, Marta C Marques, Konstantin Loeser, André Gollowitzer 1 2, Stephan Permann, Jana Gerstmeier, Stefan Lorkowski, Hermann Stuppner, Ulrike Garscha, Tiago Rodrigues, Gonçalo J L Bernardes, Daniela Schuster, Denis Séraphin, Pascal Richomme, Antonietta Rossi, Alexander S Mosig, Fiorentina Roviezzo, Oliver Werz, Jean-Jacques Helesbeux, Andreas Koeberle

J Med Chem . 2021 Aug 12;64(15):11496-11526. doi: 10.1021/acs.jmedchem.1c00806. Epub 2021 Jul 19.

Abstract

Endogenous long-chain metabolites of vitamin E (LCMs) mediate immune functions by targeting 5-lipoxygenase (5-LOX) and increasing the systemic concentrations of resolvin E3, a specialized proresolving lipid mediator. SAR studies on semisynthesized analogues highlight α-amplexichromanol (27a), which allosterically inhibits 5-LOX, being considerably more potent than endogenous LCMs in human primary immune cells and blood. Other enzymes within lipid mediator biosynthesis were not substantially inhibited, except for microsomal prostaglandin E₂ synthase-1. Compound 27a is metabolized by sulfation and β-oxidation in human liver-on-chips and exhibits superior metabolic stability in mice over LCMs. Pharmacokinetic studies show distribution of 27a from plasma to the inflamed peritoneal cavity and lung. In parallel, 5-LOX-derived leukotriene levels decrease, and the inflammatory reaction is suppressed in reconstructed human epidermis, murine peritonitis, and experimental asthma in mice. Our study highlights 27a as an orally active, LCM-inspired drug candidate that limits inflammation with superior potency and metabolic stability to the endogenous lead.

Chikako Kiyose, Haruka Takeuchi, Yoshimi Yabe, Tomoki Nojima, Mana Nagase, Chie Takahashi-Muto, Rieko Tanaka-Yachi

J Oleo Sci . 2021 Aug 6. doi: 10.5650/jos.ess21124. Online ahead of print.

Abstract

The study aim was to evaluate the potential anti-inflammatory effects of vitamin E analogs, especially α-tocopherol and δ-tocopherol. We used male C57BL/6JJcl mice, which were divided into four groups: the control (C), high-fat and high-sucrose diet (H), high-fat and high-sucrose diet+α-tocopherol (Ha) and high-fat and high-sucrose diet+δ-tocopherol (Hd) groups. The mice were fed for 16 weeks. To the high-fat and high-sucrose diet, 800 mg/kg of α-tocopherol or δ-tocopherol was added more. The final body weight was significantly higher in the H group than in the C group. On the other hand, the final body weight was drastically lower in the Ha group and Hd group than in the H group. However, the energy intake was not significantly different among all groups. Therefore, we assumed that α-tocopherol and δ-tocopherol have potential anti-obesity effect. Besides, inflammatory cytokine gene expression was significantly higher in the epididymal fat of the H group than in the C group. These results showed that inflammation was induced by epididymal fat of mice fed a high-fat and high-sucrose diet for 16 weeks. Unfortunately, addition of α-tocopherol or δ-tocopherol to the diet did not restrain inflammation of epididymal fat. Investigation of the anti-inflammatory effects of α-tocopherol or δ-tocopherol in co-cultured 3T3-L1 cells and RAW264.7 cells showed that δ-tocopherol inhibited increased gene expression of the inflammatory cytokines, IL-1β, IL-6, and iNOS. These results suggest that an anti-inflammatory effect in the δ-tocopherol is stronger than that in the α-tocopherol in vitro. We intend to perform an experiment by in vivo sequentially in the future.