The Antioxidant Activity of Tocotrienols Compared with Some Synthetic Antioxidant

The changes in content of fatty acids were studied every three months along the storage’s period, after adding an equal concentration (200 mg/Kg) of the natural antioxidant Tocotrienols (α-, β-, γ- and δ-T3) and of the synthetic one (BHT, BHA, AP) to four samples of different vegetable oils (sunflower oil, soybean oil, corn oil and olive oil). Then the oxidized and non-oxidized FAMEs were calculated to determine the antioxidant activity (AOA). The results showed that there was difference in AOA depending on the antioxidant of used. Tocotrienols were relatively weak compared with the synthetic antioxidant in all different types of oil. The AOA for each antioxidant was differed in different oil types. It was the most in the sunflower oil compared with the rest different oil types, while it was the lower for corn oil for all antioxidant. The AOA for BHA was the highest for different oil types compared with other antioxidants, and the δ-T3 had the lowest, while the rest anti-oxidants were in the following order: (BHA, BHT, AP, α-T3, β-T3, γ-T3, δ-T3).

Antioxidant status following postprandial challenge of two different doses of tocopherols and tocotrienols

Objective:Tocotrienols(T3s)have been hypothesized to have greater antioxidant capacity than tocopherols(Ts)due to differences in biokinetics that affect their absorption and function.The present trial compares the antioxidant effectiveness following postprandial challenge of two different doses ofα-T or palm T3-rich fraction(TRF)treatments and evaluates their dose-response effects on antioxidant status.Methods:Ten healthy volunteers were given four different doses of vitamin E formulations(268 mgα-T,537 mgα-T,263 mg TRF or 526 mg TRF)in a cross-over postprandial trial.Blood was sampled at 0,2,4,5,6 and 8 hours after meal consumption and plasma antioxidant status including total glutathione,superoxide dismutase,malondialdehyde(MDA),ferric reducing antioxidant potential and trolox-equivalent antioxidant capacity,was analyzed.Results:Supplementation with the different doses of eitherα-T or TRF did not significantly improve overall antioxidant status.There was no significant difference in overall antioxidant status among treatments at the different doses compared.However,a significant dose-response effect was observed for plasma MDA throughout the 8-hour postprandial period.MDA was significantly lower after the 537 mgα-T treatment,compared to the 268 mgα-T treatment;it was also lower after the 526 mg TRF treatment compared to the 263 mg TRF treatment(P<0.05).Conclusion:T3 andα-T demonstrated similar antioxidant capacity,despite markedly lower levels of T3 in blood and lipoproteins,compared toα-T.

Vitamin E in the management of pancreatic cancer: A scoping review

Pancreatic cancer is the leading cause of cancer mortality worldwide.Research investigating effective management strategies for pancreatic cancer is ongoing.Vitamin E,consisting of both tocopherol and tocotrienol,has demonstrated debatable effects on pancreatic cancer cells.Therefore,this scoping review aims to summarize the effects of vitamin E on pancreatic cancer.In October 2022,a literature search was conducted using PubMed and Scopus since their inception.Original studies on the effects of vitamin E on pancreatic cancer,including cell cultures,animal models and human clinical trials,were considered for this review.The literature search found 75 articles on this topic,but only 24 articles met the inclusion criteria.The available evidence showed that vitamin E modulated proliferation,cell death,angiogenesis,metastasis and inflammation in pancreatic cancer cells.However,the safety and bioavailability concerns remain to be answered with more extensive preclinical and clinical studies.More in-depth analysis is necessary to investigate further the role of vitamin E in the management of pancreatic cancers.

The role of antioxidants and pro-oxidants in colon cancer

This review focuses on the roles antioxidants and prooxidants in colorectal cancer(CRC).Considerable evidence suggests that environmental factors play key roles in the incidence of sporadic CRC.If pro-oxidant factors play an etiological role in CRC it is reasonable to expect causal interconnections between the wellcharacterized risk factors for CRC,oxidative stress and genotoxicity.Cigarette smoking,a high dietary consumption of n-6 polyunsaturated fatty acids and alcohol intake are all associated with increased CRC risk.These risk factors are all pro-oxidant stressors and their connections to oxidative stress,the intestinal microbiome,intestinal microfold cells,cyclooxygenase-2 and CRCare detailed in this review.While a strong case can be made for pro-oxidant stressors in causing CRC,the role of food antioxidants in preventing CRC is less certain.It is clear that not every micronutrient with antioxidant activity can prevent CRC.It is plausible,however,that the optimal food antioxidants for preventing CRC have not yet been critically evaluated.Increasing evidence suggests that RRR-gamma-tocopherol(the primary dietary form of vitamin E)or other"non-alpha-tocopherol"forms of vitamin E(e.g.,tocotrienols)might be effective.Aspirin is an antioxidant and its consumption is linked to a decreased risk of CRC.

Substrate-dependent inhibition of human cytochrome P450 3A catalytic activity by specific isomers of vitamin E

OBJECTIVE Lithocholic acid,which is a secondary bile acid,has been reported to be hepatotoxic and carcinogenic.It is metabolized by human cytochrome P450 3A(CYP3A)to form 3-ketocholanoic acid.A previous study suggests that vitamin E isomers(tocotrienols and tocopherols)are metabolized by CYP3 A.Given that substrates of an enzyme may competitively inhibit the enzyme,we determined whether alpha-tocotrienol,gamma-tocotrienol,delta-tocotrienol,tocotrienol-rich mixture(a mixture consisting of 25.7% d-α-tocotrienol,2.6% d-β-tocotrienol,28.6% d-γ-tocotrienol,8.4% d-δ-tocotrienol,25.6% d-α-tocopherol,and 4.3% d-α-tocomonoenol),and alpha-tocopherol inhibit human liver microsomal CYP3Aactivity,as assessed by the enzymatic conversion of lithocholic acid to 3-ketocholanoic acid and of testosterone to6β-hydroxytestosterone.METHODS Enzymatic formation of 3-ketocholanoic acid via lithocholic acid 3-oxidation was determined in pooled human liver microsomes and recombinant CYP3A4 and CYP3A5.Enzyme inhibition assay was conducted in a mixture containing potassium phosphate buffer(pH 7.4),human liver microsomes,NADPH,lithocholic acid,and various concentrations of a test chemical.The amount of 3-ketocholanoic acid formed was quantified by a novel,validated ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS-MS)method.RESULTS Lithocholic acid was metabolized to 3-ketocholanoic acid by human recombinant CYP3A4 and CYP3A5enzymes and human liver microsomes.Alpha-tocotrienol,gamma-tocotrienol,delta-tocotrienol,and tocotriernol-rich mixture,but not alpha-tocopherol,inhibited 3-ketocholanoic acid formation in human liver microsomes.Concentration-response experiments indicated that tocotrienol-rich mixture and delta-tocotrienol inhibited 3-ketocholanoic acid formation with IC50 values of 6.6±2.1μg·mL-1 and 19.0±1.0μmol·L-1,respectively.CONCLUSION Tocotrienols inhibited CYP3A-catalyzed lithocholic acid 3-oxidation but not CYP3A-catalyzed testosterone 6-beta-hydroxylation.This suggests that lithocholic acid and testosterone bind to different CYP3 Abinding sites and that tocotrienols preferentially inhibit the lithocholic acid binding site on CYP3 Aenzymes.

comparison between tocotrienol and omeprazole on gastric growth factors in stress-exposed rats

AIM To investigate and compare the effects of tocotrienol and omeprazole on gastric growth factors in rats exposed to water-immersion restraint stress(WIRS).METHODS Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil(vehicle) and the two treatment groups were given omeprazole(20 mg/kg) or tocotrienol(60 mg/kg) by oral gavage. After 28 d of treatment, rats from one control group and both treated groups were subjected to WIRS one time for 3.5 h. Gastric lesions were measured and gastric tissues were obtained to measure vascular endothelial growth factor(VEGF), epidermal growth factor(EGF), basic fibroblast growth factor(b FGF), and transforming growth factor-alpha(TGF-α) m RNA expression. RESULTS Rats exposed to WIRS for 3.5 h demonstrated the presence of considerable ulcers in the form of gastric erosion. The lesion index in the stressed control(S) group was increased(P < 0.001) compared to the tocotrienol treated and omeprazole treated groups. Stress led to a decrease in gastric VEGF(P < 0.001), b FGF(P < 0.001) and TGF-α(P < 0.001) m RNA levels and caused an increase in EGF m RNA(P < 0.001) that was statistically significant compared to the nonstressed control group. Although both treatment agents exerted similar ulcer reducing ability, only treatment with tocotrienol led to increased expression of VEGF(P = 0.008), b FGF(P = 0.001) and TGF-α(P = 0.002) m RNA.CONCLUSION Tocotrienol provides gastroprotective effects in WIRSinduced ulcers. Compared to omeprazole, tocotrienol exerts a similar protective effect, albeit through multiple mechanisms of protection, particularly through up-regulation of growth factors that assist in repair of gastric tissue injuries.

Tumor-targeted niosome as novel carrier for intravenous administration of tocotrienol

Tocotrienol(T3),the unsaturated form of vitamin E,has gained global attention due to its potent anticancer effects against a wide range of cancers.Found abundantly in palm oil[1],T3was reported to exhibit their anti-cancer properties via various pathways including anti-proliferative,anti-angiogenesis,antiinflammatory,apoptosis and improvement of immunological function[2].However,the lack of tumor specificity and rapid body clearance have restricted the clinical applications of T3[3].

Preparation and optimization of tocotrienol rich fraction(TRF)-loaded niosomes

Vesicular delivery systems have gainedmuch attention as pharmaceutical entities since their discovery.Niosomes occupy the general structure of bilayer vesicles,having a hydrophilic core shielded from one or multiple hydrophobic lipid bilayer.This unique structure enables them to both accommodate oilsoluble compounds as well as to encapsulate water-soluble drugs[1].The anticancer effects of tocotrienol were first discovered in the early 1990s when Nesaretnam et al.reported that palm oil stripped of vitamin E-promoted tumorigenesis in rats[2].

Nutrition and Applications of Rice Bran Oil: a Mini-overview

Rice bran oil is a healthy oil from many aspects.The oil has a balanced fatty acid profile comparing with many other vegetable oils.The key difference is the minor components or micronutrients or unsaponifiable matters contained in the oil that are very special and in larger percentages.The oil contains more than 1.5%oryzanol that gives nutritional and pharmaceutical functions from the studies so far.More studies are needed to demonstrate the wide functions in many aspects.The oil also contains large percentage of phytosterols which received huge amount of studies for nutritional applications.Furthermore,the oil contains tocopherols and tocotrienols,in which for the later particularly it gives many special functions including prevention of breast cancers for example.When the oil is properly processed and used in foods,those functions are more and more demonstrated in nutritional or biological studies.Thus the oil in food and pharmaceutical applications is in exploring both in academic studies and industrial practice.In this work,an overview of such progress is given.

Tocotrienol isoforms:The molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials

Tocotrienols are found in a variety of natural sources,like rice bran,annatto seeds and palm oil,and have been shown to have several health-promoting properties,particularly against chronic diseases such as cancer.The incidence of cancer is rapidly increasing around the world,not only a result of continued aging and population growth,but also due to the adoption of aspects of the Western lifestyle,such as high-fat diets and low-physical activity.The literature provides strong evidence that tocotrienols are able to inhibit the growth of various cancers,including breast,lung,ovarian,prostate,liver,brain,colon,myeloma and pancreatic cancers.These findings,along with the reported safety profile of tocotrienols in healthy human volunteers,encourage further research into these compounds’potential use in cancer prevention and treatment.The current review provided detailed information about the molecular mechanisms of action of different tocotrienol isoforms in various cancer models and evaluated the potential therapeutic effects of different vitamin E analogues on important cancer hallmarks,such as cellular proliferation,apoptosis,angiogenesis and metastasis.MEDLINE/PubMed and Scopus databases were used to identify recently published articles that investigated the anticancer effects of vitamin E derivatives in various types of cancer in vitro and in vivo along with clinical evidence of adjuvant chemopreventive benefits.Following an overview of pre-clinical studies,we describe several completed and ongoing clinical trials that are paving the way for the successful implementation of tocotrienols in cancer chemotherapy.