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1.
Int J Mol Sci ; 25(5)2024 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-38474201

RESUMEN

In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol's hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in pparγ and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Pparγ and Rxrα exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Pparγ and Rxrα protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperlipidemias , Tocotrienoles , Humanos , Ratones , Ratas , Animales , Tocotrienoles/metabolismo , Pez Cebra/metabolismo , Dieta Alta en Grasa , Hiperlipidemias/metabolismo , Aceite de Salvado de Arroz , Diabetes Mellitus Tipo 2/metabolismo , PPAR gamma/metabolismo , ARN Mensajero/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo
2.
J Integr Med ; 22(1): 1-11, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38336507

RESUMEN

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.


Asunto(s)
Neoplasias , Tocotrienoles , Humanos , Antioxidantes/farmacología , Apoptosis , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Tocotrienoles/farmacología , Tocotrienoles/uso terapéutico , Vitamina E/farmacología , Vitamina E/uso terapéutico , Ensayos Clínicos como Asunto
3.
Acta Oncol ; 62(9): 1066-1075, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37646150

RESUMEN

PURPOSE: Triplet chemotherapy might be more effective than doublet chemotherapy in metastatic colorectal cancer (mCRC), but it may also be marked by increased toxicity. To investigate whether δ-tocotrienol, a vitamin E analogue, with possible neuroprotective and anti-inflammatory effects, reduces the toxicity of triplet chemotherapy, we conducted a randomized, double-blind, placebo-controlled trial in mCRC patients receiving first-line 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI). MATERIAL AND METHODS: Seventy patients with mCRC were randomly assigned (1:1) to receive FOLFOXIRI plus either δ-tocotrienol or placebo at the Department of Oncology, Vejle Hospital, Denmark. Eligibility criteria were adenocarcinoma in the colon or rectum, age 18-75 years and ECOG performance status 0-1. FOLFOXIRI was given in eight cycles followed by four cycles of 5-fluorouracil. δ-tocotrienol 300 mg or placebo × 3 daily was added during chemotherapy and for a maximum of two years. The primary endpoint was time to hospitalization or death during treatment with chemotherapy. RESULTS: Median time to first hospitalization or death was 3.7 months in the placebo group (95% CI 1.93-not reached (NR)), and was NR in the δ-tocotrienol group (95% CI 1.87-NR) with a hazard ratio of 0.70 (95% CI 0.36-1.36). Grade 3-4 toxicities were uncommon in both groups, except for neutropenia, which occurred in 19 patients (58%) in the placebo group and 17 patients (50%) in the δ-tocotrienol group. There were no grade 3 or 4 peripheral sensory neuropathy. In the placebo group, 24 patients (71%) had oxaliplatin dose reductions compared to 17 patients (47%) in the δ-tocotrienol group (p = 0.047). CONCLUSION: The addition of δ-tocotrienol to FOLFOXIRI did not statistically significant prolong the time to first hospitalization or death compared to FOLFOXIRI plus placebo. Toxicity was manageable and not statistically different. There was a statistically significant difference in dose reductions of oxaliplatin pointing to a possible neuroprotective effect of δ-tocotrienol.


Asunto(s)
Neoplasias del Colon , Neoplasias Colorrectales , Neoplasias del Recto , Tocotrienoles , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Oxaliplatino/uso terapéutico , Bevacizumab/efectos adversos , Tocotrienoles/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina , Neoplasias del Colon/tratamiento farmacológico , Fluorouracilo/efectos adversos , Neoplasias del Recto/tratamiento farmacológico , Leucovorina/efectos adversos
4.
Nutrients ; 15(11)2023 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-37299466

RESUMEN

Rice (Oryza sativa L.) is a principal food for more than half of the world's people. Rice is predominantly consumed as white rice, a refined grain that is produced during the rice milling process which removes the bran and germ and leaves the starchy endosperm. Rice bran is a by-product produced from the rice milling process, which contains many bioactive compounds, for instance, phenolic compounds, tocotrienols, tocopherols, and γ-oryzanol. These bioactive compounds are thought to protect against cancer, vascular disease, and type 2 diabetes. Extraction of rice bran oil also generates various by-products including rice bran wax, defatted rice bran, filtered cake, and rice acid oil, and some of them exert bioactive substances that could be utilized as functional food ingredients. However, rice bran is often utilized as animal feed or discarded as waste. Therefore, this review aimed to discuss the role of rice bran in metabolic ailments. The bioactive constituents and food product application of rice bran were also highlighted in this study. Collectively, a better understanding of the underlying molecular mechanism and the role of these bioactive compounds exerted in the rice bran would provide a useful approach for the food industry and prevent metabolic ailments.


Asunto(s)
Diabetes Mellitus Tipo 2 , Ingredientes Alimentarios , Oryza , Fenilpropionatos , Tocotrienoles , Animales , Tocoferoles , Aceite de Salvado de Arroz
5.
Adv Nutr ; 14(5): 1159-1169, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37321474

RESUMEN

There are a large number of studies that have reported benefits of tocotrienol-rich fraction (TRF) in various populations with different health status. To date, no systematic reviews have examined randomized controlled trials (RCTs) on the effect of TRF supplementations specifically in patients with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aim to examine the changes in HbA1c (glycated hemoglobin), blood pressure, and serum Hs-CRP (C-reactive protein high sensitivity) levels at post-TRF supplementation. Online databases including PubMed, Scopus, OVID Medline, and Cochrane Central Register of Controlled Trials were searched from inception until March 2023 for RCTs supplementing TRF in patients with T2DM. A total of 10 studies were included in the meta-analysis to estimate the pooled effect size. The Cochrane Risk-of-Bias (RoB) Assessment Tool was utilized to evaluate the RoB in individual studies. The meta-analysis revealed that TRF supplementation at a dosage of 250-400 mg significantly decreased HbA1c (-0.23, 95% CI: -0.44, -0.02, P < 0.05, n = 754), particularly where the intervention duration is less than 6 mo (-0.47%, 95% CI: -0.90, -0.05, P < 0.05, n = 126) and where duration of diabetes is less than 10 y (-0.37, 95% CI: -0.68, -0.07, P < 0.05, n = 83). There was no significant reduction in systolic and diastolic blood pressure and serum Hs-CRP (P > 0.05). The present meta-analysis demonstrated that supplementing with TRF in patients with T2DM decreased HbA1c but does not decrease systolic and diastolic blood pressure and serum Hs-CRP.


Asunto(s)
Diabetes Mellitus Tipo 2 , Tocotrienoles , Humanos , Tocotrienoles/farmacología , Tocotrienoles/uso terapéutico , Hemoglobina Glucada , Proteína C-Reactiva/análisis , Ensayos Clínicos Controlados Aleatorios como Asunto , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Suplementos Dietéticos
6.
J Oleo Sci ; 72(7): 655-665, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37380482

RESUMEN

Vitamin E (tocopherols and tocotrienols) and γ-oryzanol are two minor constituents of rice bran oil (RBO) and are known to be potential bioactive compounds. The content of γ-oryzanol, a unique antioxidant found only in RBO, is a key factor in determining the retail price of the oil. Limitations of conventional HPLC columns for vitamin E and γ-oryzanol analysis are the alteration of these components and the time-consuming need for pretreatment of samples by saponification. High-performance size exclusion chromatography (HPSEC) equipped with a universal evaporative light scattering detector (ELSD) is a versatile tool for screening optimum mobile phase conditions because components of the sample can be separated and detected in the same run. In this work, the RBO components (triacylglycerol, tocopherols, tocotrienols, and γ-oryzanol) assessed on a single 100-Å Phenogel column using ethyl acetate/isooctane/acetic acid (30:70:0.1, v/v/v) as the mobile phase provided baseline separations (R s >1.5) with a total run time of 20 min. The HPSEC condition was then transferred to determine the content of tocopherols, tocotrienols, and γ-oryzanol in RBO products using a selective PDA detector. The limit of detection (LOD) and limit of quantification (LOQ) of α-tocopherol, α-tocotrienol, and γ-oryzanol were 0.34 and 1.03 µg/mL, 0.26 and 0.79 µg/mL and 2.04 and 6.17 µg/mL, respectively. This method was precise and accurate, with a percentage of relative standard deviation (%RSD) of the retention time of less than 0.21%. The intra-day and inter-day variations were 0.15-5.05% and 0.98-4.29% for vitamin E and γ-oryzanol, respectively. The recoveries of tocopherols, tocotrienols, and γ-oryzanol ranged between 90.75% and 107.98%. Thus, the developed HPSEC-ELSD-PDA method is a powerful analytical tool for determining the vitamin E and γ-oryzanol present in oil samples without requiring any sample pretreatment.


Asunto(s)
Tocotrienoles , Vitamina E , Aceite de Salvado de Arroz , Tocoferoles , Cromatografía en Gel
7.
Fish Shellfish Immunol ; 136: 108740, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37061070

RESUMEN

Tocotrienols have strong antioxidant properties; however, tocotrienol has not been investigated in detail in aquatic products. In this study, the anti-inflammatory and antioxidant activities of the tocotrienol-rich fraction from rice bran oil and its potential mechanism were verified in a zebrafish CuSO4 inflammation model. The in vitro antioxidant activity was evaluated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) stable radical method. The copper chelating activity was determined using the pyrocatechol violet method. Intracellular reactive oxygen species in zebrafish were detected using a fluorescent ROS probe. Transgenic Tg (lyz: DsRed2) zebrafish were used for neutrophil transmigration assays. The mRNA expression levels of antioxidant and pro-inflammatory factor genes were measured using quantitative real-time reverse transcription PCR. In the concentration range tested, 100 µg/mL TRF had the highest copper chelating activity (10%). TRF showed DPPH-free radical scavenging ability, which was 53% at 100 µg/mL TRF. TRF effectively repressed ROS generation and inhibited neutrophil migration to the inflamed site. Moreover, TRF upregulated the expression of antioxidant genes sod and gpx4b, inhibited the expression of pro-inflammatory factors tnfa and il8, and suppressed CuSO4-induced inflammation. In conclusion, TRF has significant anti-inflammatory and antioxidant properties, which supports the use of TRF as an aquatic feed additive to improve the anti-inflammatory and antioxidant capacity of aquatic products.


Asunto(s)
Antioxidantes , Tocotrienoles , Animales , Antioxidantes/farmacología , Aceite de Salvado de Arroz , Pez Cebra , Tocotrienoles/farmacología , Sulfato de Cobre , Especies Reactivas de Oxígeno , Cobre , Antiinflamatorios/farmacología , Inflamación/inducido químicamente
8.
Nutrients ; 15(4)2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36839192

RESUMEN

The increasing burden of nonalcoholic fatty liver disease (NAFLD) requires innovative management strategies, but an effective pharmacological agent has yet to be found. Apart from weight loss and lifestyle adjustments, one isomer of the vitamin E family-alpha-tocopherol-is currently recommended for nondiabetic steatohepatitis patients. Another member of the vitamin E family, tocotrienol (T3), has anti-inflammatory and antioxidant properties that reach beyond those of alpha-tocopherol, making it a potential agent for use in NAFLD management. This systematic review aimed to provide an overview of the effects of T3 supplementation on NAFLD from both clinical and preclinical perspectives. A literature search was performed in October 2022 using PubMed, Scopus and Web of Science. Original research articles reporting NAFLD outcomes were included in this review. The search located 12 articles (8 animal studies and 4 human studies). The literature reports state that T3 isomers or natural mixtures (derived from palm or annatto) improved NAFLD outcomes (liver histology, ultrasound or liver profile). However, the improvement depended on the severity of NAFLD, study period and type of intervention (isomers/mixture of different compositions). Mechanistically, T3 improved lipid metabolism and prevented liver steatosis, and reduced mitochondrial and endoplasmic reticulum stress, inflammation and ultimately liver fibrosis. In summary, T3 could be a potential agent for use in managing NAFLD, pending more comprehensive preclinical and human studies.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Tocotrienoles , Animales , Humanos , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Tocotrienoles/metabolismo , alfa-Tocoferol , Hígado/metabolismo , Vitamina E/metabolismo
9.
Inflammopharmacology ; 31(2): 877-886, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36853419

RESUMEN

Bixa orellana L. is a plant popularly known as "ucurum", "annatto", and "achiote". It is native to South America, and its seeds are an abundant source of geranylgeraniol and tocotrienols. Nanoencapsulation is a valuable technique that can decrease the drug needed to achieve an effect, decreasing potential toxicity, side effects and potentiate the anti-inflammatory effect. This study aimed to evaluate the acute toxicity of an intramuscular application of a nanodispersion containing a standardized extract from the seeds of Bixa orellana (NBO) in Wistar rats. The chemical evaluation showed δ-tocotrienol at 0.725 ± 0.062 mg/mL (72.6 ± 0.9%). The stability study showed the nanoparticles had an average size from 53.15 ± 0.64 to 59.9 ± 3.63 nm, with a polydispersity index ranging from 0.574 ± 0.032 to 0.574 ± 0.32, Zeta potential from 18.26 ± 0.59 to 19.66 ± 1.45 mV. After testing the intramuscular application of NBO with doses from 1 to 5 mg/kg in animals, it was observed that the acute treatment did not elicit any toxic effects within this range. The dose of 10 mg/kg, although not affecting hematological and biochemical parameters (CPK, LDH, myoglobin, AST, ALT, TC, TG, glucose levels, creatinine, and urea), could induce some muscle tissue changes, including leukocyte infiltration, morphological chances, and potentially necrosis. In conclusion, the results showed that the treatments devoided toxicity between 1 and 5 mg/kg.


Asunto(s)
Bixaceae , Tocotrienoles , Ratas , Animales , Ratas Wistar , Tocotrienoles/farmacología , Tocotrienoles/uso terapéutico , Antiinflamatorios/toxicidad , Semillas , Extractos Vegetales/toxicidad , Extractos Vegetales/uso terapéutico
10.
Food Res Int ; 164: 112386, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36737971

RESUMEN

The tocopherol (T) and tocotrienol (T3) profile were investigated in the present study for four hundred and eighteen plant oil samples, including thirty-one families, eighty-two species, and five cross-species. Fifteen species were dominated by tocotrienols, while sixty-seven - by tocopherols. The mean proportion of γ-T was almost half of the total tocochromanol content (49.3%) in the investigated samples, while α-T constituted to one quarter (25.0%), and the remaining other tocochromanols were present as minor constituents. A strong relationship between the taxonomic plant origin and the presence of the characteristic tocochromanol profile in oils obtained from those plants was noted. This is the first study to demonstrate that not only monocotyledonous, but also dicotyledons families can be rich in tocotrienols. The usefulness of statistical tools - principal component analysis (PCA) and hierarchical cluster analysis (HCA) for plant sample discrimination based on their tocochromanol profile was also shown.


Asunto(s)
Tocoferoles , Tocotrienoles , Humanos , Tocoferoles/análisis , Tocotrienoles/análisis , Aceites de Plantas , Análisis de Componente Principal , Análisis por Conglomerados
11.
Clin Nutr ESPEN ; 53: 60-73, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36657931

RESUMEN

BACKGROUND: Vitamin E has been investigated for its antitumor potential, including the ability to change cancer gene pathways as well as promote antioxidant and pro-oxidant activity. OBJECTIVE: Therefore, this systematic review aimed to evaluate antitumor and chemopreventive activity of different vitamin E isoforms (tocopherols and tocotrienols) through in vitro and in vivo studies. METHOD: The systematic review was registered in PROSPERO (No. CRD4202126207) and the search was carried out in four electronic databases (PubMed, Science Direct, Scopus and Web of Science) in June 2021 by three independent reviewers. The search equation used was: "Supplementation" AND ("Vitamin E" OR Tocopherol OR Tocotrienol) AND "breast cancer" AND (chemotherapy OR therapy OR prevention). In vitro studies and animal models of breast cancer supplemented with tocopherol or tocotrienol vitamers, alone or in combination, were included. RESULTS: The results revealed 8546 relevant studies that were initially identified in our search. After analysis, a total of 12 studies were eligible for this systematic review. All studies included animal models, and 5 of them also performed in vitro experiments on cancer cell lines. The studies performed supplementation with tocopherols, mixtures (tocopherols and tocotrienols) and synthetic vitamin E forms. There was an significant association of estradiol, dendritic cells and pterostilbene in combined therapy with vitamin E. Vitamin E delayed tumor development, reduced tumor size, proliferation, viability, expression of anti-apoptotic and cell proliferation genes, and upregulated pro-apoptotic genes, tumor suppressor genes and increased immune response. The effects on oxidative stress markers and antioxidant activity were conflicting among studies. Only one study with synthetic vitamin E reported cardiotoxicity, but it did not show vitamin E genotoxicity. CONCLUSION: In conclusion, vitamin E isoforms, isolated or associated, showed antitumor and chemopreventive activity. However, due to studies heterogeneity, there is a need for further analysis to establish dose, form, supplementation time and breast cancer stage.


Asunto(s)
Neoplasias , Tocotrienoles , Animales , Vitamina E/farmacología , Tocotrienoles/farmacología , Tocotrienoles/uso terapéutico , Antioxidantes/farmacología , Tocoferoles/farmacología , Neoplasias/tratamiento farmacológico , Vitaminas
12.
Graefes Arch Clin Exp Ophthalmol ; 261(6): 1587-1596, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36622408

RESUMEN

PURPOSE: Angiogenesis in diabetic retinopathy (DR) is associated with increased retinal expression of angiopoietin-2 (Ang-2) and protein kinase C (PKC). Tocotrienol-rich fraction (TRF) has been shown to reduce the expression vascular endothelial growth factor (VEGF) in several experimental models. However, its effect against other angiogenic markers such as Ang-2 and PKC in rat model of diabetes remains unknown. Therefore, we investigated the effect of TRF on the retinal vascular changes and Ang-2 and PKC expressions in rats with streptozotocin (STZ)-induced DR. METHODS: Sprague-Dawley rats were divided into normal control rats (N) which received vehicle, and diabetic rats which either received vehicle (DV) or 100 mg/kg of TRF (DT). Diabetes was induced with intraperitoneal injection of STZ (60 mg/kg body weight). Treatments were given orally, once daily, for 12 weeks after confirmation of hyperglycaemia. Fundus photographs were captured at baseline, 6- and 12-week post-STZ injection and average diameter of retinal veins and arteries were measured. At 12-week post-STZ injection, rats were euthanised, and retinae were collected for measurement of Ang-2 and PKC gene and protein expressions. RESULTS: Retinal venous and arterial diameters were significantly greater in DV compared to DT at week 12 post-STZ injection (p < 0.001 and < 0.05, respectively). The vessel diameter measurements in DT were comparable to N and this effect of TRF was associated with significantly lower Ang-2 and PKC gene and protein expressions compared to DV. CONCLUSION: Oral TRF reduces the expression of retinal angiogenic markers and preserves the retinal vascular diameter of rats with STZ-induced DR.


Asunto(s)
Diabetes Mellitus Experimental , Retinopatía Diabética , Tocotrienoles , Ratas , Animales , Aceite de Palma , Ratas Sprague-Dawley , Tocotrienoles/farmacología , Estreptozocina , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Retinopatía Diabética/complicaciones , Proteína Quinasa C/metabolismo , Vasos Retinianos
13.
Biol Trace Elem Res ; 201(6): 2843-2853, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35869376

RESUMEN

α-Tocotrienol is one of the major constituents of palm oil. It is a well-known antioxidant and cholesterol-lowering neuroprotectant. To prevent the initiation of Alzheimer's like symptoms, much attention has been shifted to the major role played by antioxidants. Previous epidemiological reports correlate the increasing incidence of developing Alzheimer's disease (AD), to the aluminum (Al) content in drinking water. Al, being a ubiquitous element, has a long history of being particularly reactive towards multiple aspects of neurobiology. So, the current study examines the effect of Al-induced behavioral, biochemical, and histopathological changes in rat brain; and the ameliorative effect of palm oil in reducing the resulting neurotoxicity. The experimental design consisted of 4 groups: control group which received rodent chow diet and water ad libitum; Al group received aluminum lactate (50 mg/kg bw); Al + palm oil group was administered with Al (50 mg/kg bw) and palm oil (60 mg/kg bw); and palm oil group received palm oil (60 mg/kg bw). Al was given by oral gavage once daily for 6 weeks and palm oil was administered intraperitoneally. After 6 weeks of supplementation, Al + palm oil group showed significantly lower malondialdehyde (MDA) content, but higher superoxide dismutase (SOD), catalase (CAT), GST, and GPx activity as compared to Al group. Al group has significantly higher level of MDA content, but lower SOD, CAT, GST, and GPx activity as compared to control group. In conclusion, this study suggested that palm oil was effective in preventing the Al-induced brain damage in rats.


Asunto(s)
Compuestos de Aluminio , Encéfalo , Lactatos , Aceite de Palma , Aceite de Palma/farmacología , Lactatos/toxicidad , Compuestos de Aluminio/toxicidad , Encéfalo/metabolismo , Antioxidantes , Tocotrienoles
14.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36362316

RESUMEN

Vascular dementia (VaD) is a serious global health issue and type 2 diabetes mellitus (T2DM) patients are at higher risk. Palm oil tocotrienol-rich fraction (TRF) exhibits neuroprotective properties; however, its effect on VaD is not reported. Hence, we evaluated TRF effectiveness in T2DM-induced VaD rats. Rats were given a single dose of streptozotocin (STZ) and nicotinamide (NA) to develop T2DM. Seven days later, diabetic rats were given TRF doses of 30, 60, and 120 mg/kg orally for 21 days. The Morris water maze (MWM) test was performed for memory assessment. Biochemical parameters such as blood glucose, plasma homocysteine (HCY) level, acetylcholinesterase (AChE) activity, reduced glutathione (GSH), superoxide dismutase (SOD) level, and histopathological changes in brain hippocampus and immunohistochemistry for platelet-derived growth factor-C (PDGF-C) expression were evaluated. VaD rats had significantly reduced memory, higher plasma HCY, increased AChE activity, and decreased GSH and SOD levels. However, treatment with TRF significantly attenuated the biochemical parameters and prevented memory loss. Moreover, histopathological changes were attenuated and there was increased PDGF-C expression in the hippocampus of VaD rats treated with TRF, indicating neuroprotective action. In conclusion, this research paves the way for future studies and benefits in understanding the potential effects of TRF in VaD rats.


Asunto(s)
Demencia Vascular , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Tocotrienoles , Ratas , Animales , Aceite de Palma , Tocotrienoles/farmacología , Tocotrienoles/uso terapéutico , Demencia Vascular/tratamiento farmacológico , Demencia Vascular/etiología , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Acetilcolinesterasa/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Superóxido Dismutasa/metabolismo , Aprendizaje por Laberinto
15.
Food Res Int ; 161: 111821, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36192958

RESUMEN

The present study investigated the changes in fat soluble nutraceuticals, phenolics and antioxidant activity in extrudates of whole maize flour processed at 20 %, 25 % and 30 % feed moisture (M). Bioaccessibility of them in extrudates was also investigated at 20 % M. Extrusion resulted in a significant reduction in the content of components and antioxidant activity. Retention of phytosterols was more (77 %-100 %) followed by phenolics and flavonoids in extrudates. Reducing power decreased more than threefold, while DPPH radical scavenging activity and total antioxidant activity were half of its activity observed in raw. In bioaccessible fraction, the content of stigmasterol, ß-sitosterol and flavonoids was higher than in raw while phenolics and antioxidant activity were unchanged. Bioaccessibility of carotenoids, phytosterols, phenolics, and flavonoids, as well as antioxidant activity was high, except tocopherols and tocotrienols. Overall, extrusion of maize flour with 20 % M enhanced bioaccessibility most of fat solubles, phenolics and antioxidants activity.


Asunto(s)
Fitosteroles , Tocotrienoles , Antioxidantes , Carotenoides , Suplementos Dietéticos , Flavonoides , Fenoles/análisis , Estigmasterol , Tocoferoles , Zea mays/química
16.
Biomolecules ; 12(10)2022 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-36291569

RESUMEN

Supplementation of omega-3 fatty acids is considered a valuable strategy to supply the low intake of these fatty acids. Thus, the safety of the supplements is an important milestone. Because of that, we analyzed 20 unflavored supplements sold in the French market for fatty acid and triglyceride composition, for EPA and DHA, and for tocol content, as well as for oxidative status. This study found that only 2.5% of the supplements did not meet their label claims for omega-3 content. TAG analysis showed high variability among the triglyceride distribution, and the same trend was also noticed for the tocol content; in fact, a high variability of the distribution of the six tocols (four tocopherols and two tocotrienols) was found among the samples. Of the tested products, all of them complied with peroxide value, p-anisidine value, and Totox values established by the Global Organization for EPA and DHA Omega-3s (GOED) and were not oxidized.


Asunto(s)
Ácidos Grasos Omega-3 , Tocotrienoles , Ácido Eicosapentaenoico/análisis , Ácidos Docosahexaenoicos/análisis , Ácidos Grasos Omega-3/análisis , Suplementos Dietéticos/análisis , Ácidos Grasos , Triglicéridos , Tocoferoles , Peróxidos , Aceites de Pescado
17.
Nutrients ; 14(20)2022 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-36296960

RESUMEN

Previous studies have demonstrated the anticancer activities of tocotrienol on several types of cancer, but its effects on chondrosarcoma have never been investigated. Therefore, this study aims to determine the anticancer properties of annatto tocotrienol (AnTT), γ-tocotrienol (γ-T3) and δ-tocotrienol (δ-T3) on human chondrosarcoma SW1353 cells. Firstly, the MTT assay was performed to determine the half-maximal inhibitory concentration (IC50) of tocotrienol on SW1353 cells after 24 h treatment. The mode of cell death, cell cycle analysis and microscopic observation of tocotrienol-treated SW1353 cells were then conducted according to the respective IC50 values. Subsequently, RNAs were isolated from tocotrienol-treated cells and subjected to RNA sequencing and transcriptomic analysis. Differentially expressed genes were identified and then verified with a quantitative PCR. The current study demonstrated that AnTT, γ-T3 and δ-T3 induced G1 arrest on SW1353 cells in the early phase of treatment (24 h) which progressed to apoptosis upon 48 h of treatment. Furthermore, tocotrienol-treated SW1353 cells also demonstrated large cytoplasmic vacuolation. The subsequent transcriptomic analysis revealed upregulated signalling pathways in endoplasmic reticulum stress, unfolded protein response, autophagy and transcription upon tocotrienol treatment. In addition, several cell proliferation and cancer-related pathways, such as Hippo signalling pathway and Wnt signalling pathway were also significantly downregulated upon treatment. In conclusion, AnTT, γ-T3 and δ-T3 possess promising anticancer properties against chondrosarcoma cells and further study is required to confirm their effectiveness as adjuvant therapy for chondrosarcoma.


Asunto(s)
Condrosarcoma , Tocotrienoles , Humanos , Tocotrienoles/farmacología , Transcriptoma , Línea Celular Tumoral , Vitamina E/farmacología , Apoptosis , Proliferación Celular , Condrosarcoma/tratamiento farmacológico , Condrosarcoma/genética
18.
Biomed Pharmacother ; 153: 113533, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36076612

RESUMEN

Oxidative stress, a key player in diabetic retinopathy (DR), is associated with retinal cell apoptosis. This study investigated the effect of tocotrienol-rich fraction (TRF), a potent antioxidant, towards visual behaviour, retinal morphology, cells apoptosis and redox status in streptozotocin (STZ)-induced DR rats. Sprague-Dawley rats were divided into 3 groups: non-diabetic (N), was injected with citrate buffer intraperitoneally, diabetic treated with vehicle (DV), and diabetic treated with TRF (DT), were injected with STZ intraperitoneally (55 mg/kg) to induce diabetes. DT received 100 mg of TRF/kg orally for 12-weeks, whereas DV and N received vehicle. The general and visual-behaviour responses were assessed at week 12 in an open field arena. Rats were then sacrificed, and retinae were processed for haematoxylin and eosin (H&E) and terminal transferase-mediated dUTP nick end-labelling (TUNEL) staining. Retinal antioxidant, lipid peroxidation and anti-apoptotic markers were measured. The general and visual-behaviour responses in DT were comparable to N. Retinal thickness and cell counts were lower in DV and DT compared to N. Lower number of TUNEL-positive cells were observed in DT compared to DV (1.48-fold, p < 0.001) which correlated with retinal caspase-3 expression (2.31-fold, p < 0.001). The retinal oxidative stress in DT was lower than DV as indicated by higher reduced glutathione (2.10-fold, p < 0.05), superoxide dismutase (1.12-fold, p < 0.05) and catalase (1.40-fold, p < 0.001), and lower malondialdehyde (2.54-fold, p < 0.001). In conclusion, oral TRF (100 mg/kg) supplementation for 12-weeks reduces retinal oxidative stress in STZ-induced DR rats, which in turn reduces retinal cell apoptosis and protects retinal morphology. These findings were associated with preservation of the visual-behaviour responses.


Asunto(s)
Diabetes Mellitus Experimental , Retinopatía Diabética , Estreptozocina , Tocotrienoles , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/inducido químicamente , Retinopatía Diabética/tratamiento farmacológico , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Estreptozocina/metabolismo , Estreptozocina/farmacología , Superóxido Dismutasa/metabolismo , Tocotrienoles/farmacología , Tocotrienoles/uso terapéutico
19.
Daru ; 30(2): 427-441, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36136247

RESUMEN

PURPOSE: Association between vitamins C (VC)/ E (VE) and cancer survival is inconsistent. This systematic review is aimed to summarize trials for effects of VC/VE on cancer survival. METHODS: Relevant English trials were retrieved from PubMed, Cochrane Library, Embase, Web of Science, Scopus databases, and Clinicaltrials.gov through 21/June/2022. Inclusion criteria were all trials which assessed sole/combinations intake of VC/VE on survival rate, mortality, or remission of any cancer. Exclusion criteria were observational and animal studies. RESULTS: We reached 30 trials conducted on 38,936 patients with various cancers. Due to severe methodological heterogeneity, meta-analysis was impossible. High dose VC + chemotherapy or radiation was safe with an overall survival (OS) 182 days - 21.5 months. Sole oral or intravenous high dose VC was safe with non-significant change in OS (2.9-8.2 months). VE plus chemotherapy was safe, resulted in stabling diseases for 5 years in 70- 86.7% of patients and OS 109 months. It was found 60% and 16% non-significant reductions in adjusted hazard ratio (HR) deaths or recurrence by 200 mg/d tocotrienol + tamoxifen in breast cancer, respectively. Sole intake of 200-3200 mg/d tocotrienol before resectable pancreatic cancer was safe and significantly increased cancer cells' apoptosis. Combination VC and VE was non-significantly reduced 7% in rate of neoplastic gastric polyp. CONCLUSION: Although our study is supported improvement of survival and progression rates of cancers by VC/VE, more high quality trials with large sample sizes are required to confirm. PROSPERO REGISTRATION NUMBER: CRD42020152795.


Asunto(s)
Antineoplásicos , Neoplasias , Tocotrienoles , Antineoplásicos/uso terapéutico , Ácido Ascórbico/farmacología , Neoplasias/tratamiento farmacológico , Tamoxifeno , Vitaminas
20.
Int J Mol Sci ; 23(16)2022 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-36012567

RESUMEN

Fungal pathogens capable of producing mycotoxins are one of the main threats to the cultivation of cereals and the safety of the harvested kernels. Improving the resistance of crops to fungal disease and accumulation of mycotoxins is therefore a crucial issue. Achieving this goal requires a deep understanding of plant defense mechanisms, most of them involving specialized metabolites. However, while numerous studies have addressed the contribution of phenylpropanoids and carotenoids to plant chemical defense, very few have dealt with tocochromanols. Tocochromanols, which encompass tocopherols and tocotrienols and constitute the vitamin E family, are widely distributed in cereal kernels; their biosynthetic pathway has been extensively studied with the aim to enrich plant oils and combat vitamin E deficiency in humans. Here we provide strong assumptions arguing in favor of an involvement of tocochromanols in plant-fungal pathogen interactions. These assumptions are based on both direct effects resulting from their capacity to scavenge reactive oxygen species, including lipid peroxyl radicals, on their potential to inhibit fungal growth and mycotoxin yield, and on more indirect effects mainly based on their role in plant protection against abiotic stresses.


Asunto(s)
Micotoxinas , Tocotrienoles , Grano Comestible/metabolismo , Humanos , Estrés Fisiológico , Tocoferoles/metabolismo , Tocotrienoles/metabolismo
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