Therapeutic effects of intranasal tocotrienol-rich fraction on rhinitis symptoms in platelet-activating factor induced allergic rhinitis

Cheryl Wei Ling Teo, Stephanie Jia Ying Png, Yee Wei Ung, Wei Ney Yap

Allergy Asthma Clin Immunol . 2022 Jun 13;18(1):52


Background: Platelet-activating factor (PAF) has been suggested to be a potent inflammatory mediator in Allergic rhinitis (AR) pathogenesis. Vitamin E, an essential nutrient that comprises tocopherol and tocotrienol, is known as a potential therapeutic agent for airway allergic inflammation. This study aimed to investigate the beneficial effects of intranasal Tocotrienol-rich fraction (TRF) on PAF-induced AR in a rat model.

Methods: Sprague Dawley rats were randomly assigned into 3 groups: Control, PAF-induced AR and PAF-induced AR with TRF treatment. To induce AR, 50 μl of 16 μg/ml PAF was nasally instilled into each nostril. From day 1 to 7 after AR induction, 10 μl of 16 μg/μl TRF was delivered intranasally to the TRF treatment group. Complete upper skulls were collected for histopathological evaluation on day 8.

Results: The average severity scores of AR were significantly higher in the PAF-induced AR rats compared to both control and PAF-induced AR with TRF treatment. The histologic examination of the nasal structures showed moderate degree of inflammation and polymorphonuclear cells infiltration in the lamina propria, mucosa damage and vascular congestion in the PAF-induced AR rats. TRF was able to ameliorate the AR symptoms by restoring the nasal structures back to normal. H&E staining demonstrated a statistically significant benefit upon TRF treatment, where minimal degree of inflammation, and a reduction in the infiltration of polymorphonuclear cells, mucosa damage and vascular congestion were observed.

Conclusion: TRF exhibited symptomatic relief action in AR potentially due to its antioxidant, anti-inflammatory and anti-allergic properties.

The possible effects of α-tocopherol against amiodarone-treated lungs in rats: vimentin detection, lipid peroxidation assay, and histological and ultrastructural evaluations

Mohamed Samir Ahmed Zaki, Attalla F El-Kott, Hussah I M AlGwaiz, Shehata F Shehata, Muhammad Alaa Eldeen, Mohamed Andarawi, Refaat A Eid, Eman M Abd-Ella

Environ Sci Pollut Res Int . 2022 Apr 2. doi: 10.1007/s11356-022-19883-8. Online ahead of print.

The purpose of this study was to learn more about the pathogenesis of amiodarone (AD) on alveoli and also the possible preventive effect of α-tocopherol (α-T) against these hazards. Rats were divided into 4 groups, one of which acted as a control, the second received α-T, the third AD, and the fourth AD and α-T for 2 weeks. Light microscopy (LM), immunohistochemistry, transmission electron microscopy (TEM), and malondialdehyde (MDA) activity were analyzed in sections of lung tissue. Alveoli of lung tissue AD examined with LM showed dilatation of alveolar spaces, aggregation of red blood cells, and narrowing of alveolar septa. When stained with vimentin (VIM), alveoli showed a positive reaction in the majority and a moderate reaction in others. In the pneumocytes of the type II, some cytoplasmic vesicles had been deflated, whereas others contained lamellar bodies, a damaged nucleus, and vesicles in their heterochromatin. In the interstitial space, collagen fibers with aggregation of red blood cells and a disrupted blood-air barrier were detected. In rat lung alveoli treated with AD and α-T, the alveolar septum thickened and the alveolar spaces expanded as estimated. The alveoli of this group had more or less intact type I and II pneumocytes and a better appearance of the blood-air barrier. In the cells of the alveolar lining, the VIM staining leads to a diffuse positive response. Finally, lung parenchyma also improved, suggesting that α-T may help minimize the effects of AD.

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Serum level and clinical significance of vitamin E in pregnant women with allergic rhinitis

Sihai Wu, Aiping Wang

J Chin Med Assoc . 2022 Mar 25. doi: 10.1097/JCMA.0000000000000723. Online ahead of print.


Background: Allergic rhinitis is a frequent disorder during pregnancy, while in children it is triggered by significantly lower serum vitamin E level. This research aimed to investigate whether serum vitamin E level exhibited clinical significance in pregnant women with allergic rhinitis.

Methods: In this study, 37 pregnant women with allergic rhinitis and 35 healthy pregnant women were recruited. Allergic rhinitis severity was analyzed by the Total Nasal Symptom Score (TNSS) questionnaire. Blood samples were collected to evaluate serum vitamin E, interleukin (IL) and total IgE levels.

Results: In pregnant women with allergic rhinitis, serum level of vitamin E was significantly lower than in healthy pregnant women. Serum vitamin E level in pregnant women with allergic rhinitis showed negative correlation with TNSS, IL-13, IL-4, and total IgE levels.

Conclusion: In conclusion, this research has demonstrated that pregnant women with allergic rhinitis showed significantly lower serum level of vitamin E. The decreased vitamin E showed correlation with the pathogenesis of allergic rhinitis in pregnant women.

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Potential “Therapeutic” Effects of Tocotrienol-Rich Fraction (TRF) and Carotene “Against” Bleomycin-Induced Pulmonary Fibrosis in Rats via TGF-β/Smad, PI3K/Akt/mTOR and NF-κB Signaling Pathways

Yifei Lu, Yihan Zhang, Zhenyu Pan, Chao Yang, Lin Chen, Yuanyuan Wang, Dengfeng Xu, Hui Xia, Shaokang Wang, Shiqing Chen, Yoong Jun Hao, Guiju Sun

Nutrients . 2022 Mar 5;14(5):1094. doi: 10.3390/nu14051094.


Background: Pulmonary fibrosis (PF) is a chronic, progressive, and, ultimately, terminal interstitial disease caused by a variety of factors, ranging from genetics, bacterial, and viral infections, to drugs and other influences. Varying degrees of PF and its rapid progress have been widely reported in post-COVID-19 patients and there is consequently an urgent need to develop an appropriate, cost-effective approach for the prevention and management of PF.

Aim: The potential “therapeutic” effect of the tocotrienol-rich fraction (TRF) and carotene against bleomycin (BLM)-induced lung fibrosis was investigated in rats via the modulation of TGF-β/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways.

Design/methods: Lung fibrosis was induced in Sprague-Dawley rats by a single intratracheal BLM (5 mg/kg) injection. These rats were subsequently treated with TRF (50, 100, and 200 mg/kg body wt/day), carotene (10 mg/kg body wt/day), or a combination of TRF (200 mg/kg body wt/day) and carotene (10 mg/kg body wt/day) for 28 days by gavage administration. A group of normal rats was provided with saline as a substitute for BLM as the control. Lung function and biochemical, histopathological, and molecular alterations were studied in the lung tissues.

Results: Both the TRF and carotene treatments were found to significantly restore the BLM-induced alterations in anti-inflammatory and antioxidant functions. The treatments appeared to show pneumoprotective effects through the upregulation of antioxidant status, downregulation of MMP-7 and inflammatory cytokine expressions, and reduction in collagen accumulation (hydroxyproline). We demonstrated that TRF and carotene ameliorate BLM-induced lung injuries through the inhibition of apoptosis, the induction of TGF-β1/Smad, PI3K/Akt/mTOR, and NF-κB signaling pathways. Furthermore, the increased expression levels were shown to be significantly and dose-dependently downregulated by TRF (50, 100, and 200 mg/kg body wt/day) treatment in high probability. The histopathological findings further confirmed that the TRF and carotene treatments had significantly attenuated the BLM-induced lung injury in rats.

Conclusion: The results of this study clearly indicate the ability of TRF and carotene to restore the antioxidant system and to inhibit proinflammatory cytokines. These findings, thus, revealed the potential of TRF and carotene as preventive candidates for the treatment of PF in the future.

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Effect of α-tocopherol in alleviating the lipopolysaccharide-induced acute lung injury via inhibiting nuclear factor kappa-B signaling pathways

Mu Hu, Jielai Yang, Yang Xu

Bioengineered . 2022 Feb;13(2):3958-3968. doi: 10.1080/21655979.2022.2031399.


Acute respiratory distress syndrome (ARDS) leads to the acute lung injury (ALI), a form of diffused alveolars injury, accompanied by severe inflammation and oxidative damage of alveolar epithelial cells. α-Tocopherol (α-TOH), one of the eight isoforms of vitamin E, is a natural antioxidant-free radical. We aimed to understand the effect of α-TOH and mechanism involved in inducing the ALI. Lipopolysaccharide (LPS) is injected into the trachea of mice to generate ALI mouse models. α-TOH was used to administrate the mice intragastrically to detect the expression of inflammatory factors and antioxidant molecules by enzyme linked immunosorbent assay, hematoxylin-eosin staining and immunohistochemical staining. Mouse alveolar epithelial cell line (MLE-12 cells) was used to determine the effect of α-TOH on alveolar epithelial cells. Inflammatory factors such as, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α shows significant increase in the lung tissues of the mice induced by LPS and reduction in the expressions of superoxide dismutase (SOD)1/2 and glutathione peroxidase (GSH-Px). After treatment with α-TOH, the inflammation and oxidative stress levels shows substantial reduction in the lung tissues of the mice. Moreover, α-TOH also increases the proliferation ability of MLE-12 cells in vitro and reduces apoptosis level. In addition, α-TOH reduces p65 phosphorylation and nuclear translocation in alveolar epithelial cells in vivo and in vitro, thus, inhibiting the activity of the nuclear factor kappa-B (NF-κB) signaling pathway. α-TOH reduces the inflammation and oxidative stress of lung tissue by inhibiting the NF-κB signaling pathway, thereby alleviating the LPS-induced ALI.

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Change in plasma alpha-tocopherol associations with attenuated pulmonary function decline and with CYP4F2 missense variation

Jiayi Xu, Kristin A Guertin, Nathan C Gaddis, Anne H Agler, Robert S Parker, Jared M Feldman, Alan R Kristal, Kathryn B Arnold, Phyllis J Goodman, Catherine M Tangen, Dana B Hancock, Patricia A Cassano

Am J Clin Nutr . 2022 Jan 18;nqac013. doi: 10.1093/ajcn/nqac013. Online ahead of print.


Background: Vitamin E (vitE) is hypothesized to attenuate age-related decline in pulmonary function.

Objectives: We investigated the association between change in plasma vitE (∆vitE) and pulmonary function decline (forced expiratory volume in the first second [FEV1]) and examined genetic and non-genetic factors associated with ∆vitE.

Design: We studied 1,144 men randomized to vitE in the Selenium and Vitamin E Cancer Prevention Trial. ∆vitE was the difference between baseline and year 3 vitE concentrations measured with gas chromatography-mass spectrometry. FEV1 was measured longitudinally by spirometry. We genotyped 555 men (vitE-only arm) using the Illumina MEGAex array. We used mixed-effects linear regression modeling to examine the ∆vitE-FEV1 association.

Results: Higher ∆vitE was associated with lower baseline α-tocopherol, higher baseline γ-tocopherol, higher baseline free cholesterol, European ancestry (vs. African) (all P < 0.05), and the minor allele of a missense variant in CYP4F2 (rs2108622-T; 2.4 µmol/L higher ∆vitE, SE = 0.8, P = 0.0032). Higher ∆vitE was associated with attenuated FEV1 decline, with stronger effects in adherent participants (≥80% of supplements consumed): a statistically significant ∆vitE × time interaction (P = 0.014) indicated that a 1-unit increase in ∆vitE was associated with a 2.2 mL/year attenuation in FEV1 decline (SE = 0.9). The effect size for 1 standard deviation higher ∆vitE (+4 µmol/mmol free-cholesterol-adjusted α-tocopherol) is ∼¼ of the effect of one year of aging, but in the opposite direction. The ∆vitE-FEV1 association was similar in never smokers (2.4 mL/year attenuated FEV1 decline, SE = 1.0, P = 0.017, n = 364), and current smokers (2.8 mL/year, SE = 1.6, P = 0.079, n = 214), but there was little to no effect in former smokers (-0.64 mL/year, SE = 0.9, P = 0.45, n = 564).

Conclusions: Greater response to vitamin E supplementation was associated with attenuated FEV1 decline. The response to supplementation differed by rs2108622 such that individuals with the C allele, compared to the T allele, may need a higher dietary intake to reach the same plasma vitamin E concentration.

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Vitamin E relieves chronic obstructive pulmonary disease by inhibiting COX2-mediated p-STAT3 nuclear translocation through the EGFR/MAPK signaling pathway

Hui Zhao, Jiannan Gong, Lifang Li, Shuyin Zhi, Guang Yang, Pingping Li, Ruina Li, Jianqiang Li

Lab Invest . 2021 Nov 19. doi: 10.1038/s41374-021-00652-z. Online ahead of print.


Patients with chronic obstructive pulmonary disease (COPD) are characterized by an imbalance between oxidant enzymes and antioxidant enzymes. In the present study, we explored the protective effect of vitamin E on COPD and the underlying mechanisms. Targets of vitamin E were predicted by bioinformatics analysis. After establishing cigarette smoke (CS)-induced COPD rats, the expression levels of epidermal growth factor receptor (EGFR), cyclooxygenase 2 (COX2), and transcriptional activity of signal transducer and activator of transcription 3 (STAT3) were measured. Additionally, the effects of vitamin E on CS-induced COPD were explored by assessing inflammation, the reactive oxygen species (ROS), the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA), viability of human bronchial epithelioid (HBE) cells, and the expression of EGFR/MAPK pathway-related factors after loss- and gain- function assays. Vitamin E alleviated COPD. Vitamin E inhibited MAPK signaling pathway through decreasing EGFR expression. Additionally, vitamin E suppressed CS-induced HBE cell damage. Functionally, vitamin E attenuated CS-induced inflammation, apoptosis, and ROS by inhibiting the EGFR/MAPK axis, thereby inhibiting COX2-mediated p-STAT3 nuclear translocation. Moreover, overexpression of COX2 attenuated the protective effect of vitamin E on COPD rats. The present study shows that vitamin E inhibits the expression of COX2 by negatively regulating the EGFR/MAPK pathway, thereby inhibiting the translocation of phosphorylated STAT3 to the nucleus and relieving COPD.

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Is the lower serum level of vitamin E associated with pregnant women with allergic rhinitis?

Yiu-Tai Li, Wen-Ling Lee, Peng-Hui Wang

J Chin Med Assoc . 2021 Aug 1;84(8):739-740. doi: 10.1097/JCMA.0000000000000566.


It is well known that adequate maintenance or support of nutrition during pregnancy, including essential and trace elements and calorie intake, is a critical dimension not only to maintain peak health and performance of themselves but also for the lifelong health of the offspring.1–7 Malnutrition often results in inadequate protein intake, fewer calories, and deficiency of certain-type essential trace elements. Intake of enough calorie can be easily monitored by measuring gestational weight gain (GWG) in the entire pregnancy period or more accurately estimated by separating GWG according to the different trimesters3; however, it is hard to define whether these pregnant women have adequate dietary intake or meet recommendations for vitamins D, C, A, B complex, K, and E, as well as folate, choline, iron, calcium, potassium, magnesium, zinc, and other essential trace elements (minerals or essential amino acids and so on), partly because of difficulty to measure and monitor these essential trace elements, and partly because of overlooking its important and critical role on both maternal and offspring’s outcome.1,2,4–6 Additionally, these certain-type essential trace elements sometimes make physicians or healthcares confused, based on the presence of multifaced functions of these elements. It has been reported that continuous supplementation of vitamin E throughout offspring lifespan provides beneficial effects to the offspring, but one meta-analysis using experimental models and observational investigations, which are involved with more than 135 000 participants in 19 trials carried out between 1966 and 2004 did not support the above-mentioned findings, based on a significantly increasing mortality from all causes when high dosage vitamin E supplements are given as a supplement throughout their lifespan.

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Administration of vitamin E attenuates airway inflammation through restoration of Nrf2 in a mouse model of asthma

Quang Luu Quoc, Tra Cao Thi Bich, Seo-Hee Kim, Hae-Sim Park, Yoo Seob Shin

J Cell Mol Med . 2021 Jul;25(14):6721-6732. doi: 10.1111/jcmm.16675. Epub 2021 Jun 4.


Accumulating evidence reveals that ROS is one of the key mediators that contribute to the development of asthma. Studies on antioxidants have shown to have beneficial effects on asthma management. However, we still do not know the precise mechanism, and the effects depend on age. This study was conducted to assess the levels of ROS and the effect of antioxidants in younger and older mice using an eosinophilic asthma model. We analyzed airway hyperresponsiveness (AHR), cytokines in bronchoalveolar lavage fluid (BALF), inflammatory cell counts, and the expression levels of NFκB, Nrf2, EPx, and EDN in the lung tissue, as well as the level of ROS in the lung tissue and BALF. The degree of eosinophilia and the levels of IL-5, ROS, and NFκB were significantly increased, whereas the endogenous levels of vitamin E and Nrf2 were decreased in the lung and BALF in the older mice compared to younger mice. The administration of vitamin E attenuated AHR, airway inflammation, and the level of IL-13 and ROS and enhanced the Nrf2 level in the older mice compared to the younger mice. Taken together, vitamin E treatment may have the therapeutic potential through restoration of the Nrf2 level, especially in elderly asthma.

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The association of vitamin D and vitamin E levels at birth with bronchopulmonary dysplasia in preterm infants

Haiyan Ge, Weina Liu, Huimin Li, Ming Zhang, Mengbin Zhang, Chao Liu, Yanxia Qiao

Pediatr Pulmonol . 2021 Jul;56(7):2108-2113. doi: 10.1002/ppul.25414. Epub 2021 Apr 20.


Background: Despite improvements made in neonatal care, bronchopulmonary dysplasia (BPD) is still the most common respiratory disease in preterm infants. The relationship between the blood contents of vitamin D/E in premature infants and BPD is still controversial.

Methods: Preterm infants were recruited as the research subjects. On the basis of the inclusion and exclusion criteria, a total of 133 eligible cases were finally included. A total of 63 preterm infants with a clear diagnosis of BPD and 5 preterm infants who died before the diagnosis of BPD were in the case group, and 65 non-BPD preterm infants with equivalent baseline characteristics were in the control group. The BPD group included 38 cases in Grade Ⅰ, 18 cases in Grade Ⅱ, and 12 cases in Grade Ⅲ. The contents of vitamin D and E in the cord blood of different groups were detected by high-performance liquid chromatography and enzyme-linked immunosorbent assay. Correlation analysis adopted the Pearson correlation analytic method.

Results: The serum vitamin D and E levels at birth were remarkably lower in the BPD group than the non-BPD group, both of which were also correlated with the severity of BPD. The vitamin D and E contents were negatively correlated with the oxygen support duration required for premature infants with BPD.

Conclusion: This study deepens our understanding of the field of BPD pathogenesis by demonstrating an association between vitamin D/E deficiency and BPD severity, suggesting that vitamin D and E might have potential clinical value in the prognosis and treatment of BPD.

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