Developing functional markers for vitamin E biosynthesis in oil palm

Yajing Dou, Wei Xia, Annaliese S Mason, Dongyi Huang, Xiwei Sun, Haikuo Fan, Yong Xiao

PLoS One . 2021 Nov 19;16(11):e0259684. doi: 10.1371/journal.pone.0259684. eCollection 2021.

Abstract

Vitamin E is essential for human health and plays positive roles in anti-oxidation. Previously, we detected large variation in vitamin E content among 161 oil palm accessions. In this study, twenty oil palm accessions with distinct variation in vitamin E contents (171.30 to 1 258.50 ppm) were selected for genetic variation analysis and developing functional markers associated with vitamin E contents. Thirty-seven homologous genes in oil palm belonging to vitamin E biosynthesis pathway were identified via BLASTP analysis, the lengths of which ranged from 426 to 25 717 bp (average 7 089 bp). Multiplex PCR sequencing for the 37 genes found 1 703 SNPs and 85 indels among the 20 oil palm accessions, with 226 SNPs locating in the coding regions. Clustering analysis for these polymorphic loci showed that the 20 oil palm accessions could be divided into five groups. Among these groups, group I included eight oil palm accessions whose vitamin E content (mean value: 893.50 ppm) was far higher than other groups (mean value 256.29 to 532.94 ppm). Correlation analysis between the markers and vitamin E traits showed that 134 SNP and 7 indel markers were significantly (p < 0.05) related with total vitamin E content. Among these functional markers, the indel EgTMT-1-24 was highly correlated with variation in vitamin E content, especially tocotrienol content. Our study identified a number of candidate function associated markers and provided clues for further research into molecular breeding for high vitamin E content oil palm.

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.

Abstract

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.

Ram Lakhan, Manoj Sharma, Kavita Batra, Frazier B Beatty

Healthcare (Basel) . 2021 Nov 18;9(11):1573. doi: 10.3390/healthcare9111573.

Abstract

With the aging population, dementia emerges as a public health concern. In 2012, the Health and Retirement Study found that 8.8% of adults over 65 years suffered from dementia. The etiopathogenesis and treatment of dementia are not well understood. Antioxidant properties of Vitamin E and its major elements tocopherols and tocotrienols have been reported to be effective in slowing down the progression of dementia from its initial stage of Mild cognitive impairment (MCI). Therefore, the current review aims to explore the role of vitamin E on MCI. A literature search using the key words “Vitamin E, tocopherols, tocotrienols, and mild cognitive impairment” was conducted in MEDLINE (PubMed), CINAHL, and Google Scholar. The inclusion criteria were: (1) articles published in the past ten years; (2) published in English language; (3) published in peer-reviewed journals; and (4) descriptive and epidemiological or evaluation studies. Articles published prior to 2010, focused on other forms of dementia than MCI, grey literature and non-peer-reviewed articles were excluded. A total of 22 studies were included in the narrative synthesis. The results were equivocal. Eleven studies showed some level of the neuroprotective effect of Vitamin E, tocopherols and tocotrienols on the progression of MCI. The mixed results of this review suggest further exploration of the possible protective effects of Vitamin E on the development of dementia. Future studies can be conducted to decipher antioxidant properties of vitamin E and its association with slowing down the cognitive decline.

Nurul 'Izzah Ibrahim, Hasnul 'Iffah Mohd Noor, Ahmad Naqib Shuid, Sharlina Mohamad, Mohd Maaruf Abdul Malik, Putri Ayu Jayusman, Ahmad Nazrun Shuid, Isa Naina Mohamed

Front Pharmacol . 2021 Nov 18;12:706747. doi: 10.3389/fphar.2021.706747. eCollection 2021.

Abstract

Osteoporosis, the most common bone disease, is associated with compromised bone strength and increased risk of fracture. Previous studies have shown that oxidative stress contributes to the progression of osteoporosis. Specifically, for postmenopausal osteoporosis, the reduction in estrogen levels leads to increased oxidative stress in bone remodeling. Tocotrienol, a member of vitamin E that exhibits antioxidant activities, has shown potential as an agent for the treatment of osteoporosis. Most studies on the osteoprotective effects of tocotrienols had used the oral form of tocotrienols, despite their low bioavailability due the lack of transfer proteins and high metabolism in the liver. Several bone studies have utilized tocotrienol combined with a nanocarrier to produce a controlled release of tocotrienol particles into the system. However, the potential of delivering tocotrienol-nanocarrier combination through the intraosseous route has never been explored. In this study, tocotrienol was combined with a nanocarrier, poly lactic-co-glycolic acid (PLGA), and injected intraosseously into the bones of ovariectomized rats to produce targeted and controlled delivery of tocotrienol into the bone microenvironment. This new form of tocotrienol delivery was compared with the conventional oral delivery in terms of their effects on bone parameters. Forty Sprague-Dawley rats were divided into five groups. The first group was sham operated, while other groups were ovariectomized (OVX). Following 2 months, the right tibiae of all the rats were drilled at the metaphysis region to provide access for intraosseous injection. The estrogen group (OVX + ESTO) and tocotrienol group (OVX + TTO) were given daily oral gavages of Premarin (64.5 mg/kg) and annatto-tocotrienol (60 mg/kg), respectively. The locally administered tocotrienol group (OVX + TTL) was given a single intraosseous injection of tocotrienol-PLGA combination. After 8 weeks of treatment, both OVX + TTO and OVX + TTL groups have significantly lower bone markers and higher bone mineral content than the OVX group. In terms of bone microarchitecture, both groups demonstrated significantly higher trabecular separation and connectivity density than the OVX group (p < 0.05). Both groups also showed improvement in bone strength by the significantly higher stress, strain, stiffness, and Young’s modulus parameters. In conclusion, daily oral tocotrienol and one-time intraosseous injection of tocotrienol-PLGA combination were equally effective in offering protection against ovariectomy-induced bone changes.

Santanu Sasidharan, Timir Tripathi, Prakash Saudagar

ACS Omega . 2021 Nov 16;6(47):31396-31403. doi: 10.1021/acsomega.1c05046. eCollection 2021 Nov 30.

Abstract

Despite global therapeutic advancements, tropical parasitic infections like trypanosomiasis and leishmaniasis continue to be a major health concern in developing countries. These two tropical infectious diseases lead to enormous economic loss, significant disability, and morbidity, accounting for over one million deaths per year worldwide. The causative parasites, which shuttle between an insect vector and a mammalian host, thrive either in the bloodstream or in the intramacrophage environments. Essentially, the parasites live in an environment of oxidative stress and therefore require metabolic pathways to counterbalance the host immune response and survive the adverse conditions. Apart from the trypanothione pathway elucidated in the parasites, there exists a tocopherol pathway that functions to scavenge the reactive chemical species. This pathway, unique to photosynthetic organisms, is essential for the parasite’s survival, though the enzymes involved remain largely uncharacterized. Consequently, an understanding of the origin of the pathway and where and how the interconnected tocopherol pathway functions may result in the identification of promising and potential therapeutic interventions to combat these deadly diseases. Recent works underline the presence of the tocopherol pathway in trypanosomatids and hypothesize that trypanosomatids may be tocopherol prototrophs. This review focuses on the biosynthesis of tocopherols in Trypanosoma and Leishmania in light of the current evidence.

Qing Jiang

Free Radic Biol Med . 2021 Nov 14;S0891-5849(21)00806-6. doi: 10.1016/j.freeradbiomed.2021.11.012. Online ahead of print.

Abstract

Natural forms of vitamin E comprise four tocopherols and four tocotrienols. During the last twenty years, there have been breakthroughs in our understanding of vitamin E metabolism and biological activities of vitamin E metabolites. Research has established that tocopherols and tocotrienols are metabolized via ω-hydroxylase (CYP4F2)-initiated side chain oxidation to form 13′-hydroxychromanol and 13′-carobyxychromanol (13′-COOH). 13′-COOHs are further metabolized via β-oxidation and sulfation to intermediate carboxychromanols, terminal metabolite carboxyethyl-hydroxychroman (CEHC), and sulfated analogs. Animal and human studies show that γ-, δ-tocopherol and tocotrienols are more extensively metabolized than α-tocopherol (αT), as indicated by higher formation of CEHCs and 13′-COOHs from non-αT forms than those from αT. 13′-COOHs are shown to be inhibitors of cyclooxygenase-1/-2 and 5-lipoxygenase and much stronger than CEHCs for these activities. 13′-COOHs inhibit cancer cell growth, modulate cellular lipids and activate peroxisome proliferator-activated receptor-γ and pregnane X receptor. Consistent with mechanistic findings, αT-13′-COOH or δTE-13′-COOH, respective metabolites of αT or δ-tocotrienol, show anti-inflammatory and cancer-preventive effects, modulates the gut microbiota and prevents β-amyloid formation in mice. Therefore, 13′-COOHs are a new class of bioactive compounds with anti-inflammatory and anti-cancer activities and potentially capable of modulating lipid and drug metabolism. Based on the existing evidence, this author proposes that metabolites may contribute to disease-preventing effects of γ-, δ-tocopherol and tocotrienols. The role of metabolites in αT’s actions may be somewhat limited considering controlled metabolism of αT because of its association with tocopherol-transport protein and less catabolism by CYP4F2 than other vitamin E forms.

Ali Qusay Khalid, Saatheeyavaane Bhuvanendran, Kasthuri Bai Magalingam, Premdass Ramdas, Mangala Kumari, Ammu Kutty Radhakrishnan

Nutrients . 2021 Nov 12;13(11):4056. doi: 10.3390/nu13114056.

Abstract

The last decade has witnessed tremendous growth in tocotrienols (T3s) research, especially in the field of oncology, owing to potent anticancer property. Among the many types of cancers, colorectal cancer (CRC) is growing to become a serious global health threat to humans. Chemoprevention strategies in recent days are open to exploring alternative interventions to inhibit or delay carcinogenesis, especially with the use of bioactive natural compounds, such as tocotrienols. This scoping review aims to distil the large bodies of literature from various databases to identify the genes and their encoded modulations by tocotrienols and to explicate important mechanisms via which T3s combat CRC. For this scoping review, research papers published from 2010 to early 2021 related to T3s and human CRC cells were reviewed in compliance with the PRISMA guidelines. The study included research articles published in English, searchable on four literature databases (Ovid MEDLINE, PubMed, Scopus, and Embase) that reported differential expression of genes and proteins in human CRC cell lines following exposure to T3s. A total of 12 articles that fulfilled the inclusion and exclusion criteria of the study were short-listed for data extraction and analysis. The results from the analysis of these 12 articles showed that T3s, especially its γ and δ analogues, modulated the expression of 16 genes and their encoded proteins that are associated with several important CRC pathways (apoptosis, transcriptional dysregulation in cancer, and cancer progression). Further studies and validation work are required to scrutinize the specific role of T3s on these genes and proteins and to propose the use of T3s to develop adjuvant or multi-targeted therapy for CRC.

Deniz Tazeoğlu, Cüneyt Akyüz, Mehmet Gökçeimam, Gülçin Harman Kamalı, Ayhan Özsoy, Servet Rüştü Karahan

Ulus Travma Acil Cerrahi Derg . 2021 Nov;27(6):605-612. doi: 10.14744/tjtes.2020.89054.

Abstract

Background: Acute pancreatitis is an inflammatory disease accompanied by pancreatic inflammation characterized by acinar cell damage and leukocyte infiltration in the tissue. At present, mortality and morbidity rates are high despite the current treatment of pancreatitis; therefore, new studies and treatment studies are needed. In this study, the effects of alpha-tocopherol on different doses of L-arginine-induced experimental acute pancreatitis model were investigated.

Methods: Thirty adult male Sprague-Dawley albino rats were randomly divided into four groups; control (sham) group (n=6), acute pancreatitis group (n=8), low-dose alpha-tocopherol (200 mg/kg once intraperitoneal [IP]) group (n=8), and high dose alpha-tocopherol (400 mg/kg once ip) group (n=8). Experimental acute pancreatitis model was created by a single IP dose of 5 g/kg of L-arginine. Alpha-tocopherol was administered in a single dose intraperitoneally, 30 min before the creation of the experimental model of acute pancreatitis induced by L-arginine induction in Groups 3 and 4. Tissue and blood samples were taken under anesthesia 72 h after L-arginine injection; then the rats were sacrificed by decapitation. Serum amylase, lipase, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-alpha, and C-reactive protein (CRP) levels were examined. Pancreatic tissue samples were examined under a light microscope for histopathological examination.

Results: When the acute pancreatitis group (Group 2) was compared to the control group (Group 1), serum amylase, lipase, IL-1β, IL-6, TNF-alpha, and CRP levels were all significantly increased (p<0.05 for all). Histopathological examination showed significant difference in edema (p<0.001) and inflammation (p=0.007) scores. When the low (Group 3) and high (Group 4) dose alpha-tocopherol groups were compared to Group 2, amylase, lipase, IL-1β, IL-6, TNF-alpha, and CRP parameters were statistically significantly lower (p<0.05 for all). In the histopathological comparison of Groups 2, 3, and 4, edema and inflammation scores were decreased in Groups 3 and 4 compared to Group 2. Comparing Group 4 to Group 3, lipase (p<0.01), IL-6 (p=0.038), and TNF-alpha (p=0.002) levels were significantly decreased; no significant difference was observed in the histopathological evaluation.

Conclusion: Alpha-tocopherol was found to reduce inflammation and pancreatic damage in acute pancreatitis and was more effective in high doses.

Zeru Lou, Ke Wu, Yizi Xu, Xiaokun Cai, Fang Tian, Yingyi Mao, Yanrong Zhao, Meiqin Cai

Wei Sheng Yan Jiu . 2021 Nov;50(6):914-918. doi: 10.19813/j.cnki.weishengyanjiu.2021.06.007.

Abstract

Objective: The study aimed to investigate the contents and isomer composition of vitamin E in mature milk in different regions of China.

Methods: Simultaneously recruited 604 lactating mothers aged(29.58±3.43) from Shanghai, Guangzhou, Tianjin, Chengdu, Lanzhou and Changchun cities. They were mainly primiparas with good education background. A total number of 604 mature milk samples was collected. The contents of α-, γ-, δ-tocopherols and the stereoisomers of α-tocopherol were determined by high performance liquid chromatography(HPLC).

Results: The M(P25, P75) concentrations of α-tocopherol, RRR-α-tocopherol, γ-tocopherol and δ-tocopherol in Chinese mature milk were 3.16(2.29, 4.16)mg/L, 2.57(1.77, 3.48)mg/L, 0.89(0.58, 1.27)mg/L and 0.17(0.09, 0.27)mg/L, respectively. The total α-TE level was 3.09(2.22, 4.10)mg/L with statistically regional differences(P<0.001). RRR-α-tocopherol was the predominated stereoisomers of α-tocopherol, accounting for 83.17%(76.36%, 88.43%). The proportion of RRR in Tianjin mature milk was significantly lower than that in Lanzhou(77.11% vs. 86.16%, P<0.001) while breast milk samples from other regions had similar RRR-α-tocopherol proportions(82.82%-85.39%).

Conclusion: Vitamin E content in mature milk was mainly composed of α-tocopherol. Even though the contents of tocopherols have large regional differences, RRR-α-tocopherol was predominated form in all breast milk samples. It is suggested that RRR-α-tocopherol was the main active form of vitamin E in the early stage of life.

Aman B Upaganlawar, Nitu L Wankhede, Mayur B Kale, Mohit D Umare, Aayush Sehgal, Sukhbir Singh, Saurabh Bhatia, Ahmed Al-Harrasi, Agnieszka Najda, Renata Nurzyńska-Wierdak, Simona Bungau, Tapan Behl

Biomed Pharmacother . 2021 Nov;143:112146. doi: 10.1016/j.biopha.2021.112146. Epub 2021 Sep 8.

Abstract

Epilepsy is the most common neurological disorder, affecting nearly 50 million people worldwide. The condition can be manifested either due to genetic predisposition or acquired from acute insult which leads to alteration of cellular and molecular mechanisms. Evaluating the latest and the current knowledge in regard to the mechanisms underlying molecular and cellular alteration, hyperexcitability is a consequence of an imbalanced state wherein enhance excitatory glutamatergic and reduced inhibitory GABAergic signaling is considered to be accountable for seizures associated damage. However, neurodegeneration contributing to epileptogenesis has become increasingly appreciated. The components at the helm of neurodegenerative alterations during epileptogenesis include GABAergic neuronal and receptor changes, neuroinflammation, alteration in axonal transport, oxidative stress, excitotoxicity, and other cellular as well as functional changes. Targeting neurodegeneration with vitamin E as an antioxidant, anti-inflammatory and neuroprotective may prove to be one of the therapeutic approaches useful in managing epilepsy. In this review, we discuss and converse about the seizure-induced episodes as a link for the development of neurodegenerative and pathological consequences of epilepsy. We also put forth a summary of the potential intervention with vitamin E therapy in the management of epilepsy.