Update on the Anti-Cancer Potency of Tocotrienols and α-Tocopheryl Polyethylene Glycol 1000 Succinate on Leukemic Cell Lines

Constantina Constantinou, Christiana Charalambous, Dimitrios Kanakis, Ourania Kolokotroni, Andreas I Constantinou

Nutr Cancer . 2020 Jul 22;1-7. doi: 10.1080/01635581.2020.1797128. Online ahead of print.


The natural isoforms of vitamin E γ-tocotrienol (γ-ΤΤ) and δ-tocotrienol (δ-ΤΤ) and the synthetic derivative α-tocopheryl polyethylene glycol 1000 succinate (TPGS) have promising anticancer potency in a variety of cancer cell lines and animal models of cancer. Ongoing clinical trials are investigating the anti-tumor effectiveness of TTs in combination with chemotherapeutic agents in patients suffering from breast, colon, non-small cell lung and ovarian cancers. Despite extensive research on different types of cancer, the anticancer potency of TTs and TPGS has not been thoroughly investigated in leukemias. Given the fact that certain types of leukemias have very low survival rates and that patients suffer significantly from the toxic side effects of chemotherapeutic drugs, there is a need to develop novel treatments with increased specificity against cancer cells and reduced toxicity to the patients. The aim of this review is to report current evidence on the anticancer potency of TTs and TPGS on leukemic cells lines and to discuss future studies that could be carried out to investigate the role of these agents in the management of leukemias.

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Acylphloroglucinol and tocotrienol derivatives from the fruits of Garcinia paucinervis

Xue Tan, Fangfang Zhong, Hongli Teng, Qingqing Li, Yitong Li, Zhinan Mei, Yu Chen, Guangzhong Yang

Fitoterapia . 2020 Jul 21;146:104688. doi: 10.1016/j.fitote.2020.104688. Online ahead of print.


Three undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) and three tocotrienols derivatives, named as paucinochymol A-F (1-3 and 10-12), together with six known PPAPs, were isolated from the fruits of Garcinia paucinervis. Their structures and absolute configurations were determined by extensive NMR analysis and electronic circular dichroism (ECD) calculation methods. Paucinochymol A (1) is the first compound of this type featuring a ω-isogeranyl with tetrahydrofuran unit at C-1. Paucinochymols D and E (4-5) belong to rare tocotrienol with one glorious macrocyclic and an ortho-quinone moiety, respectively. The antiproliferative and anti-inflammatory activities of all isolates were tested. Four PPAPs exhibited weak inhibitory activities against three human cancer cell lines (HepG2, T98, MCF-7) with IC50 values ranging from 10.0 to 16.0 μM. Paucinochymol D (10) displayed moderate inhibitory effects against nitric oxide (NO) production with the IC50 value of 19.8 μM.

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Inflammatory Diseases and Vitamin E-What Do We Know and Where Do We Go?

Maria Wallert, Lisa Börmel, Stefan Lorkowski

Mol Nutr Food Res . 2020 Jul 21;e2000097. doi: 10.1002/mnfr.202000097. Online ahead of print.


Inflammation-driven diseases and related comorbidities, such as the metabolic syndrome, obesity, fatty liver disease, and cardiovascular diseases cause significant global burden. There is a growing body of evidence that nutrients alter inflammatory responses and can therefore make a decisive contribution to the treatment of these diseases. Recently, the inflammasome, a cytosolic multiprotein complex, has been identified as a key player in inflammation and the development of various inflammation-mediated disorders, with nucleotide-binding domain and leucine-rich repeat pyrin domain (NLRP) 3 being the inflammasome of interest. Here an overview about the cellular signaling pathways underlying nuclear factor “kappa-light-chain-enhancer” of activated B-cells (NF-κB)- and NLRP3-mediated inflammatory processes, and the pathogenesis of the inflammatory diseases atherosclerosis and non-alcoholic fatty liver disease (NAFLD) is provided; next, the current state of knowledge for drug-based and dietary-based interventions for treating cardiovascular diseases and NAFLD is discussed. To date, one of the most important antioxidants in the human diet is vitamin E. Various in vitro and in vivo studies suggest that the different forms of vitamin E and also their derivatives have anti-inflammatory activity. Recent publications suggest that vitamin E-and possibly metabolites of vitamin E-are a promising therapeutic approach for treating inflammatory diseases such as NAFLD.

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Platelet function in stroke/transient ischemic attack patients treated with tocotrienol

Andrew Slivka, Cameron Rink, David Paoletto, Chandan K Sen

FASEB J . 2020 Jul 20. doi: 10.1096/fj.201902216RR. Online ahead of print.


The purpose of this study was to characterize the effects of tocotrienol form of vitamin E (TCT) on platelet function in patients with stroke or transient ischemic attack (TIA). A double blind, randomized, single center phase II clinical trial was conducted comparing placebo (PBO) and 400 and 800 mg TCT daily for a year in 150 patients with a sentinel ischemic stroke or TIA event in the prior 6 months. Platelet function was measured at baseline and then, at 3 month intervals for a year, using light transmission aggregometry. The incidence of aspirin resistance in aspirin-treated patients or platelet inhibition in patients on clopidogrel alone was compared between the three treatment groups. Results showed that in patients taking aspirin and clopidogrel, the incidence of aspirin resistance was significantly decreased from 40% in PBO-treated patients to 9% in the 400 mg TCT group and 25% in the TCT 800 mg group (P = .03). In conclusion, patients on aspirin and clopidogrel had a higher incidence of aspirin resistance than all patients treated with aspirin alone and TCT decreased the frequency of aspirin resistance in this group.

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Influence of specific management practices on blood selenium, vitamin E, and beta-carotene concentrations in horses and risk of nutritional deficiency

Mariya O Pitel, Erica C McKenzie, Jennifer L Johns, Robert L Stuart

J Vet Intern Med . 2020 Jul 20. doi: 10.1111/jvim.15862. Online ahead of print.


Background: Selenium or alpha-tocopherol deficiency can cause neuromuscular disease. Beta-carotene has limited documentation in horses.

Objective: To evaluate the effect of owner practices on plasma beta-carotene concentration and risk of selenium and alpha-tocopherol deficiencies.

Animals: Three-hundred and forty-nine adult (≥1 year), university and privately owned horses and mules.

Methods: Cross-sectional study. Whole blood selenium, plasma alpha-tocopherol, and plasma beta-carotene concentrations were measured once. Estimates of daily selenium and vitamin E intake, pasture access, and exercise load were determined by owner questionnaire. Data were analyzed using t tests, Mann-Whitney tests, parametric or nonparametric analysis of variance (ANOVA), Kruskal-Wallis test, Spearman’s correlation and contingency tables (P < .05).

Results: Nearly 88% of the horses received supplemental selenium; 71.3% received ≥1 mg/d. Low blood selenium concentration (<80 ng/mL) was identified in 3.3% of horses, and 13.6% had marginal concentrations (80-159 ng/mL). Non-supplemented horses were much more likely to have low blood selenium (odds ratio [OR], 20.2; 95% confidence interval [CI], 9.26-42.7; P < .001). Supplemental vitamin E was provided to 87.3% of horses; 57.7% received ≥500 IU/d. Deficient (<1.5 μg/mL) and marginal (1.5-2.0 μg/mL) plasma (alpha-tocopherol) occurred in 15.4% and 19.9% of horses, respectively. Pasture access (>6 h/d) and daily provision of ≥500 IU of vitamin E was associated (P < .001) with higher plasma alpha-tocopherol concentrations. Plasma beta-carotene concentration was higher in horses with pasture access (0.26 ± 0.43 versus 0.12 ± 0.13 μg/mL, P = .003).

Conclusions and clinical importance: Suboptimal blood selenium and plasma alpha-tocopherol concentrations occurred in 16.7% and 35.5% of horses, respectively, despite most owners providing supplementation. Inadequate pasture access was associated with alpha-tocopherol deficiency, and reliance on selenium-containing salt blocks was associated with selenium deficiency.

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Summary and evidence grading of over-the-counter scar treatments

Konstantin V Grigoryan, Jeremy T Kampp

Int J Dermatol . 2020 Jul 20. doi: 10.1111/ijd.15060. Online ahead of print.


Background: Many products claiming to improve scar appearance are readily available on the Internet. Data behind these claims are often difficult to find or summarize. Patients often ask their surgeon for advice for scarring postdermatologic surgery.

Objective: We aim to review the evidence behind several advertised products and techniques that claim to improve postsurgical scarring.

Methods: A PubMed search was performed using products and methods claiming to improve scar appearance along with the terms “scar” and “scarring”.

Results: Published literature on scar massage, taping of scars, silicone gel and sheeting, onion-based extract products, and vitamin E was reviewed. Silicone gel/sheeting as well as taping have the most evidence to help improve scarring, but even then the evidence is conflicting and weak.

Conclusion: Online advertising may tempt patients to buy and trial products to help minimize scarring, although the evidence for the effectiveness of these products is absent to minimal. Dermatologists must be aware of these products to maintain effective patient counseling.

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Application and Efficacy of Vitamin E-Bonded Polysulfone Membrane in Acute Blood Purification Therapy

Eiichi Himeno, Shigeru Goto, Satoru Inoue, Yoshihiro Hatanaka, Satoshi Hagiwara, Shigekiyo Matsumoto, Takaaki Kitano

Blood Purif . 2020 Jul 17;1-7. doi: 10.1159/000508276. Online ahead of print.


Introduction: Acute blood purification therapy (BPT) has been evaluated in the context of intensive care for serious conditions related to systemic inflammation, but its mechanism and efficacy are not fully understood.

Objective: This study examined the feasibility of using vitamin E-bonded polysulfone membranes (VEPS) for BPT in a LPS-induced rat model of systemic inflammation.

Methods: To evaluate the efficacy of BPT with a VEPS membrane, polysulfone (PS) membranes conventionally used in intensive care were bonded with the antioxidant vitamin E and used in a rat model of lipopolysaccharide (LPS)-induced systemic inflammation. BPT using a PS membrane (PS group) or a VEPS membrane (VEPS group) was performed 6 h after administration of LPS. Extracorporeal circulation was established in normal rats as a control (sham group). Survival rates, histology of lung specimens, and levels of myeloperoxidase (MPO) and high mobility group box-1 (HMGB-1) were examined in each group.

Results: Survival rates at 24 h after LPS administration were 100% in the VEPS group and 50% in the PS group. Pulmonary architecture was largely maintained and the level of infiltration of inflammatory cells remained moderate in the VEPS group. Levels of active MPO before and after BPT were significantly higher in the PS and VEPS groups than in the sham group, with no significant differences between the PS and VEPS groups. HMGB-1 levels were significantly elevated after BPT in the PS group.

Conclusions: This study demonstrated that use of the VEPS membrane for BPT increased survival rate and reduced lung injury in a rat model of systemic inflammatory response syndrome (SIRS), suggesting the possible use of VEPS membranes in the treatment of serious conditions related to systemic inflammation.

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Nutrient pattern of unsaturated fatty acids and vitamin E increase resting metabolic rate of overweight and obese women

Habib Yarizadeh, Leila Setayesh, Caroline Roberts, Mir Saeed Yekaninejad, Khadijeh Mirzaei

Int J Vitam Nutr Res . 2020 Jul 16;1-9. doi: 10.1024/0300-9831/a000664. Online ahead of print.


Objectives: Obesity plays an important role in the development of chronic diseases including cardiovascular disease and diabetes. A low resting metabolic rate (RMR) for a given body size and composition is a risk factor for obesity, however, there is limited evidence available regarding the association of nutrient patterns and RMR. The aim of this study was to determine the association of nutrient patterns and RMR in overweight and obese women. Study design: This cross-sectional study was conducted on 360 women who were overweight or obese. Method: Dietary intake was assessed using a semi-quantitative standard food frequency questionnaire (FFQ). Nutrient patterns were also extracted by principal components analysis (PCA). All participants were evaluated for their body composition, RMR, and blood parameters. Result: Three nutrient patterns explaining 64% of the variance in dietary nutrients consumption were identified as B-complex-mineral, antioxidant, and unsaturated fatty acid and vitamin E (USFA-vit E) respectively. Participants were categorized into two groups based on the nutrient patterns. High scores of USFA-vit E pattern was significantly associated with the increase of RMR (β = 0.13, 95% CI = 0.79 to 68.16, p = 0.04). No significant associations were found among B-complex-mineral pattern (β = -0.00, 95% CI = -49.67 to 46.03, p = 0.94) and antioxidant pattern (β = 0.03, 95% CI -41.42 to 22.59, p = 0.56) with RMR. Conclusion: Our results suggested that the “USFA-vit E” pattern (such as PUFA, oleic, linoleic, vit.E, α-tocopherol and EPA) was associated with increased RMR.

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Stereological and histopathological evaluation of doxorubicin-induced toxicity in female rats’ ovary and uterus and palliative effects of quercetin and vitamin E

M Samare-Najaf, F Zal, S Safari, F Koohpeyma, N Jamali

Hum Exp Toxicol . 2020 Jul 15;960327120937329. doi: 10.1177/0960327120937329. Online ahead of print


Doxorubicin (DOX) is a widely used chemotherapeutic agent with demonstrated reproductive toxicity. This study sought to determine the DOX-induced toxicity in the ovary and uterus and the preventive effects of quercetin (QCT) and vitamin E (Vit.E). Female rats were divided into six groups as follows: control, QCT (20 mg/kg), Vit.E (200 mg/kg), DOX (accumulative 15 mg/kg), DOX/QCT, and DOX/Vit.E. After 3 weeks, the toxicity of DOX in ovarian and uterine tissues and the potential palliative effects of QCT and Vit.E were evaluated by histopathological-stereological methods. The findings indicate a dramatic decline in the number of ovarian follicles (p < 0.001), ovarian and its associated structures volume, the volume of the uterus, its layers, and related structures (p < 0.05). Coadministration of QCT and Vit.E with DOX-treated rats demonstrated an alleviative effect on most of the studied parameters. Nevertheless, few adverse effects were recognized concerning these antioxidants administration (p < 0.05). In conclusion, the findings of this study support the protective role of these dietary supplements in the prevention of DOX-induced toxicity in uterine and ovarian tissues.

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Phytochemical Profiles of Rice and Their Cellular Antioxidant Activity Against ABAP Induced Oxidative Stress in Human Hepatocellular Carcinoma HepG2 Cells

Er Sheng Gong, Chengmei Liu, Bin Li, Wei Zhou, Hongyu Chen, Tong Li, Jianyong Wu, Zicong Zeng, Yuehua Wang, Xu Si, Yuxi Lang, Ye Zhang, Weijia Zhang, Guowen Zhang, Shunjing Luo, Rui Hai Liu

Food Chem . 2020 Jul 15;318:126484. doi: 10.1016/j.foodchem.2020.126484. Epub 2020 Feb 25.


The phytochemical contents, peroxyl radical scavenging capacities (PSCs) and cellular antioxidant activities (CAAs) of free and bound fractions of rice were reported. Black rice had the highest total phenolic content and total flavonoid content in free and bound fractions, followed by red rice, brown rice, and polished rice. Black rice contained much more free phenolic compounds than other rice samples, such as cyanidin-3-O-glucoside, protocatechuic acid, and vanillic acid. Tocopherols and tocotrienols contents were highest in red rice, then in black rice, brown rice, and polished rice. PSCs and CAAs of free and bound fractions were in the order: black rice > red rice > brown rice > polished rice, except that bound CAA of red rice was higher than that of black rice. The cellular uptake rate of free phenolics was highest in red rice, while cellular uptake rates of bound phenolics were highest in brown rice and polished rice.

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