Advancing skin delivery of α-tocopherol and γ-tocotrienol for dermatitis treatment via nanotechnology and microwave technology

Mohd Saufi Harun, Tin Wui Wong, Chee Wai Fong

Int J Pharm . 2021 Jan 25;593:120099. doi: 10.1016/j.ijpharm.2020.120099. Epub 2020 Nov 28.

Abstract

This study investigated combination nanocarrier and microwave system for α-tocopherol and γ-tocotrienol delivery against dermatitis, without skin thinning effect of steroids. The vitamin E was formulated into water-rich/water-poor nanoemulsions, and had their droplet size, zeta potential, morphology, therapeutic content, encapsulation efficiency and release, in vitro skin therapeutics/nanoemulsion penetration, retention and permeation profiles, and in vivo pharmacodynamics characteristics examined, with skin pre-treated by precision microwave when applicable. The nanoemulsions had droplet sizes <150 nm and negative zeta potential values. The skin pre-treatment by microwave (1 mW/3985 MHz) promoted therapeutics accumulation in epidermis through enhancing nanoemulsion penetration into skin. The combination nano- and microwave technologies fluidized skin lipid and protein domains with epidermal microstructures being fluidized to a greater extent than dermis, allowing a relatively high epidermal-to-dermal nanoemulsion distribution. Microwave of lower or higher than 3985 MHz brought about lower skin therapeutics/nanoemulsion accumulation due to insufficient lipid/protein domain fluidization or microwave-skin interaction limiting at skin surfaces only. Using water-rich nanoemulsion with higher therapeutic release and skin pre-treatment with 3985 MHz microwave, dermatitis was alleviated in vivo without skin thinning of standard steroid. The use of combination microwave and nanotechnology promotes vitamin delivery and translates to positive dermatitis treatment outcome that warrants future investigation.

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Production of tocotrienols in seeds of cotton (Gossypium hirsutum L.) enhances oxidative stability and offers nutraceutical potential

Shanmukh S Salimath, Trevor B Romsdahl, Anji Reddy Konda, Wei Zhang, Edgar B Cahoon, Michael K Dowd, Thomas C Wedegaertner, Kater D Hake, Kent D Chapman

Plant Biotechnol J . 2021 Jan 25. doi: 10.1111/pbi.13557. Online ahead of print.

Abstract

Upland cotton (Gossypium hirsutum L.) is an economically important multi-purpose crop cultivated globally for fibre, seed oil and protein. Cottonseed oil also is naturally rich in vitamin E components (collectively known as tocochromanols), with α- and γ-tocopherols comprising nearly all of the vitamin E components. By contrast, cottonseeds have little or no tocotrienols, tocochromanols with a wide range of health benefits. Here, we generated transgenic cotton lines expressing the barley (Hordeum vulgare) homogentisate geranylgeranyl transferase coding sequence under the control of the Brassica napus seed-specific promoter, napin. Transgenic cottonseeds had ~twofold to threefold increases in the accumulation of total vitamin E (tocopherols + tocotrienols), with more than 60% γ-tocotrienol. Matrix assisted laser desorption ionization-mass spectrometry imaging showed that γ-tocotrienol was localized throughout the transgenic embryos. In contrast, the native tocopherols were distributed unequally in both transgenic and non-transgenic embryos. α- Tocopherol was restricted mostly to cotyledon tissues and γ-tocopherol was more enriched in the embryonic axis tissues. Production of tocotrienols in cotton embryos had no negative impact on plant performance or yield of other important seed constituents including fibre, oil and protein. Advanced generations of two transgenic events were field grown, and extracts of transgenic seeds showed increased antioxidant activity relative to extracts from non-transgenic seeds. Furthermore, refined cottonseed oil from the two transgenic events showed 30% improvement in oxidative stability relative to the non-transgenic cottonseed oil. Taken together, these materials may provide new opportunities for cottonseed co-products with enhanced vitamin E profile for improved shelf life and nutrition.

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Role of Palm Oil Vitamin E in Preventing Pre-eclampsia: A Secondary Analysis of a Randomized Clinical Trial Following ISSHP Reclassification

Nurul Afzan Aminuddin, Rosnah Sutan, Zaleha Abdullah Mahdy

Front Med (Lausanne) . 2021 Jan 21;7:596405. doi: 10.3389/fmed.2020.596405. eCollection 2020.

Abstract

Background: Preeclampsia is a significant cause of maternal and perinatal mortality worldwide. Oxidative stress plays a key role in its pathophysiology, hence antioxidants such as tocotrienol may be preventive against preeclampsia. In 2018, the ISSHP revised the definition of preeclampsia. In accordance with the new definition, we report a secondary data analysis from a clinical trial comparing palm oil vitamin E in the form of tocotrienol-rich fraction (TRF) against placebo, in preventing preeclampsia. Method: A randomized double-blind controlled trial was conducted in 2002-2005 to assess the benefits of TRF in preeclampsia prevention. A total of 299 primigravidae were recruited. The intervention group was supplemented with TRF 100 mg daily in super-olein capsules, whereas the placebo group was prescribed super-olein capsules without TRF, beginning from 12 to 16 gestational weeks until delivery. The primary outcome measure was incidence of preeclampsia. Results: The total incidence of pregnancy induced hypertension (PIH) was 5%, whereas the incidence of preeclampsia was 2.3%. The odds of developing PIH (adjusted OR 0.254; 95% CI: 0.07-0.93; p-value 0.038) and preeclampsia (adjusted OR 0.030; 95% CI: 0.001-0.65; p-value 0.025) were significantly lower in the TRF arm compared to the placebo arm. Conclusion: Antenatal supplementation with palm oil vitamin E in the form of TRF is associated with significant reductions in the incidence of preeclampsia and PIH in a single urban tertiary hospital. Palm oil vitamin E deserves further scrutiny as a potential public health preventive measure against preeclampsia and PIH.

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The Health Benefits of Tocotrienol

Tocotrienols are chemicals in the vitamin E family. Unlike other forms of vitamin E, tocotrienols are less commonly found in nature. Most of the food we eat contains tocopherols instead of tocotrienols, but several types of vegetable oils, like palm oil, contain high amounts of tocotrienols. Most vitamin E supplements contain tocopherols and not tocotrienols. Studies also suggest that tocotrienol is a more potent form of vitamin E than tocopherol. Research also tells us that tocotrienol has many health benefits.

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A Phase IIb Randomized Controlled Trial Investigating the Effects of Tocotrienol-Rich Vitamin E on Diabetic Kidney Disease

Yan Yi Koay, Gerald Chen Jie Tan, Sonia Chew Wen Phang, J-Ian Ho, Pei Fen Chuar, Loon Shin Ho, Badariah Ahmad, Khalid Abdul Kadir

Nutrients . 2021 Jan 18;13(1):258. doi: 10.3390/nu13010258.

Abstract

Diabetic kidney disease (DKD) is a debilitating complication of diabetes, which develops in 40% of the diabetic population and is responsible for up to 50% of end-stage renal disease (ESRD). Tocotrienols have shown to be a potent antioxidant, anti-inflammatory, and antifibrotic agent in animal and clinical studies. This study evaluated the effects of 400 mg tocotrienol-rich vitamin E supplementation daily on 59 DKD patients over a 12-month period. Patients with stage 3 chronic kidney disease (CKD) or positive urine microalbuminuria (urine to albumin creatinine ratio; UACR > 20-200 mg/mmol) were recruited into a randomized, double-blind, placebo-controlled trial. Patients were randomized into either intervention group (n = 31) which received tocotrienol-rich vitamin E (Tocovid SupraBioTM; Hovid Berhad, Ipoh, Malaysia) 400 mg daily or a placebo group which received placebo capsules (n = 28) for 12 months. HbA1c, renal parameters (i.e., serum creatinine, eGFR, and UACR), and serum biomarkers were collected at intervals of two months. Tocovid supplementation significantly reduced serum creatinine levels (MD: -4.28 ± 14.92 vs. 9.18 ± 24.96), p = 0.029, and significantly improved eGFR (MD: 1.90 ± 5.76 vs. -3.29 ± 9.24), p = 0.011 after eight months. Subgroup analysis of 37 patients with stage 3 CKD demonstrated persistent renoprotective effects over 12 months; Tocovid improved eGFR (MD: 4.83 ± 6.78 vs. -1.45 ± 9.18), p = 0.022 and serum creatinine (MD: -7.85(20.75) vs. 0.84(26.03), p = 0.042) but not UACR. After six months post washout, there was no improvement in serum creatinine and eGFR. There were no significant changes in the serum biomarkers, TGF-β1 and VEGF-A. Our findings verified the results from the pilot phase study where tocotrienol-rich vitamin E supplementation at two and three months improved kidney function as assessed by serum creatinine and eGFR but not UACR.

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MPOB develops three palm-based technologies for commercialisation

The Malaysian Palm Oil Board (MPOB) has developed three advanced palm-based technologies for commercialisation.

In a statement on Friday, it said the first is the process and formulation of palm vitamin E/ tocotrienol-rich fraction (TRF) chewable tablet. The second is palm oil-based polyol for floor coverings for indoor and outdoor and sports flooring markets while the third is a moisturising hand sanitiser with Vitamin E. MPOB said the three are among the technologies approved by the Minister of Plantation Industries and Commodities for commercialisation.

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Patient-derived Nerve Cells May Help Advance Pompe Research

As a proof-of-concept, the team evaluated the effects of treating the cells with a lab-made GAA — obtained after infusions of Lumyzime (alglucosidase alfa), an enzyme replacement therapy — delta-tocopherol, and hydroxypropyl-beta-cyclodextrin (HPβCD). Delta-tocopherol and HPβCD are two structurally distinct small molecules previously shown to lessen disease features in cellular and animal models of lysosomal storage diseases.

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Application of Partial Hydrogenation for the Generation of Minor Tocochromanol Homologs and Functional Evaluation of Hydrogenated Tocotrienol-rich Vitamin E Oil in Diabetic Obese Mice

Fumiaki Beppu, Aimi Sakuma, Satoshi Kasatani, Yoshinori Aoki, Naohiro Gotoh

J Oleo Sci . 2021;70(1):103-112. doi: 10.5650/jos.ess20233.

Abstract

Recent research has identified minor homologs of vitamin E with one or two double bonds in the side-chain, namely tocomonoenol (T1) and tocodienol (T2), in natural products. We first explored the effectiveness of partial hydrogenation for generating minor tocochromanols from tocotrienol (T3). During hydrogenation with pure α-T3 as a substrate, the side-chain was partially saturated in a time-dependent manner, and a large amount of α-T1 and α-T2 was obtained. To investigate the beneficial effects of the hydrogenated product, we fed diabetic obese KK-A y mice with a hydrogenated T3 mixture (HT3). Feeding HT3 revealed tissue-specific accumulation of tocochromanols, ameliorated hyperglycemia and improved ratio of high-density lipoprotein cholesterol to total cholesterol in serum, with invariant body weight and fat mass. Hence, we propose that hydrogenation is a useful method for generating T1 and T2 homologs, which can be applied to explore the structure-related function of tocochromanols.

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Palm oil may help fight cancer

Research by medical experts have revealed that palm tocotrienols act on three different mechanisms in the hallmarks of cancer – tumour suppressors, immune modulation and inflammation. Malaysian Palm Oil Board (MPOB) research officer, Dr Fu Ju Yen said the hypothesis on the study conducted showed enhanced absorption of tocotrienols by eight-fold when delivered via nanocarriers.

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