The Effects of Vitamin E from Elaeis guineensis (Oil Palm) in a Rat Model of Bone Loss Due to Metabolic Syndrome

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Int J Environ Res Public Health. 2018 Aug 24;15(9). pii: E1828. doi: 10.3390/ijerph15091828.

Abstract

The beneficial effects of vitamin E in improving components of MetS or bone loss have been established. This study aimed to investigate the potential of palm vitamin E (PVE) as a single agent, targeting MetS and bone loss concurrently, using a MetS animal model. Twelve-week-old male Wistar rats were divided into five groups. The baseline group was sacrificed upon arrival. The normal group was given standard rat chow. The remaining three groups were fed with high-carbohydrate high-fat (HCHF) diet and treated with tocopherol-stripped corn oil (vehicle), 60 mg/kg or 100 mg/kg PVE. At the end of the study, the rats were evaluated for MetS parameters and bone density. After euthanasia, blood and femurs were harvested for the evaluation of lipid profile, bone histomorphometric analysis, and remodeling markers. PVE improved blood pressure, glycemic status, and lipid profile; increased osteoblast surface, osteoid surface, bone volume, and trabecular thickness, as well as decreased eroded surface and single-labeled surface. Administration of PVE also significantly reduced leptin level in the HCHF rats. PVE is a potential agent in concurrently preventing MetS and protecting bone loss. This may be, in part, achieved by reducing the leptin level and modulating the bone remodeling activity in male rats.

Read More

Exploring the potential of tocotrienol from Bixa orellana as a single agent targeting metabolic syndrome and bone loss

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Bone. 2018 Jul 7. pii: S8756-3282(18)30260-6. doi: 10.1016/j.bone.2018.07.003. [Epub ahead of print]

Abstract

Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienolhas been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.

Read More

Identifying Potential Therapeutics for Osteoporosis by Exploiting the Relationship between Mevalonate Pathway and Bone Metabolism

Wan Hasan WN, Chin KY, Jolly JJ, Abd Ghafar N, Soelaiman IN.

Endocr Metab Immune Disord Drug Targets. 2018 Apr 23. doi: 10.2174/1871530318666180423122409. [Epub ahead of print]

Abstract

BACKGROUND:

Osteoporosis is a silent skeletal disease characterized by low bone mass and destruction of skeletal microarchitecture, leading to an increased fracture risk. This occurs due to an imbalance in bone remodelling, whereby the rate of bone resorption is greater than bone formation. Mevalonate pathway, previously known to involve in cholesterol synthesis, is an important regulatory pathway for bone remodelling.

OBJECTIVE:

This review aimed to provide an overview of the relationship between mevalonate pathway and bone metabolism, as well as agents which act through this pathway to achieve their therapeutic potential.

DISCUSSION:

Mevalonate pathway produces farnesyl pyrophosphate and geranylgeranyl pyrophosphate essential in protein prenylation. An increase in protein prenylation favours bone resorption over bone formation. Non-nitrogen containing bisphosphonates inhibit farnesyl diphosphate synthase which produces farnesyl pyrophosphate. They are used as the first line therapy for osteoporosis. Statins, a well-known class of cholesterol-lowering agents, inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the mevalonate pathway. It was shown to increase bone mineral density and prevent fracture in humans. Tocotrienol is a group of vitamin E commonly found in palm oil, rice bran and annatto bean. It causes degradation of HMG-CoA reductase. Many studies demonstrated that tocotrienol prevented bone loss in animal studies but its efficacy has not been tested in humans.

CONCLUSION:

mevalonate pathway can be exploited to develop effective antiosteoporosis agents.

KEYWORDS:

bone; bone metabolism; mevalonate pathway; tocotrienol; vitamin E.

Read More

Preparation of Vitamin E-Containing High-Density Lipoprotein and Its Protective Efficacy on Macrophages.

Su M, Wang D, Chang W, Liu L, Cui M, Xu T

Assay Drug Dev Technol. 2018 Feb 22. doi: 10.1089/adt.2017.831. [Epub ahead of print]

Abstract

Atherosclerosis is a major cause for cardiovascular diseases. High-density lipoprotein (HDL) may reduce atherosclerosis through several different mechanisms. HDL is composed of lipids, cholesterol, cholesteryl esters, triglycerides, and phospholipids, mainly phosphatidylcholine plus specialized proteins called apolipoproteins (apos). In this study, we prepared vitamin E containing HDL (VE-HDL) that contains egg phosphatidylcholine, cholesterol, vitamin E, and two kinds of recombinant human apolipoproteins (rhapo)-rhapoA-I and rhapoE in vitro by the facilitation of cholate. After that, we studied the effects of VE-HDL on foam cell formation, cellular cholesterol efflux, oxidative low-density lipoprotein (oxLDL)-stimulated oxidative stress, and apoptosis of macrophages to evaluate the protective efficacy of VE-HDL on macrophages. As the results showed, we prepared a new type of reconstituent HDL with apolipoproteins and vitamin E for the first time. VE-HDL has protective efficacy on macrophages. It has the prospect of becoming a therapeutic agent on atherosclerosis in the future.

Read More

Tocotrienols: the unsaturated sidekick shifting new paradigms in vitamin E therapeutics.

Kanchi MM, Shanmugam MK, Rane G, Sethi G, Kumar AP

Drug Discov Today. 2017 Aug 5. pii: S1359-6446(17)30137-X. doi: 10.1016/j.drudis.2017.08.001. [Epub ahead of print]

Abstract

Vitamin E family members: tocotrienols and tocopherols are widely known for their health benefits. Decades of research on tocotrienols have shown they have diverse biological activities such as antioxidant, anti-inflammatory, anticancer, neuroprotective and skin protection benefits, as well as improved cognition, bone health, longevity and reduction of cholesterol levels in plasma. Tocotrienols also modulate several intracellular molecular targets and, most importantly, have been shown to improve lipid profiles, reduce total cholesterol and reduce the volume of white matter lesions in human clinical trials. This review provides a comprehensive update on the little-known therapeutic potentials of tocotrienols, which tocopherols lack in a variety of inflammation-driven diseases.

Read More

Vitamin E and caloric restriction promote hepatic homeostasis through expression of connexin 26, N-cad, E-cad and cholesterol metabolism genes.

Santolim LV, Amaral ME, Fachi JL, Mendes MF, Oliveira CA.

J Nutr Biochem. 2017 Jan;39:86-92. doi: 10.1016/j.jnutbio.2016.09.011. Epub 2016 Oct 11.

Abstract

Connexins (Cx) and cadherins are responsible for cell homeostasis. The Cx activity is directly related to cholesterol. The present work investigates whether vitamin E, with or without caloric restriction (CR), alters the mRNA expression of Cx26, Cx32, Cx43, N-cadherins (N-cads), E-cadherins (E-cads) and alpha-smooth muscle actin (α-SMA), and evaluates their relation to cholesterol metabolism in rat liver. Animals were divided into different groups: control with ad libitum diet (C), control+vitamin E (CV), aloric restriction with intake to 60% of group C (CR), and the intake of group CR+vitamin E (RV). There were increases of manganese superoxide dismutase (Mn-SOD) and glutathione S-transferase mu 1, indicating antioxidant effects of CR and vitamin E. An increase of nitric oxide in the CR group was in agreement with the Mn-SOD data. Supplementation with vitamin E, with or without CR, upregulated the expression of Cx26 mRNA and increased low-density lipoprotein cholesterol (LDL-c) in the CV group. Reductions of Cx32 and Cx43 were associated with lower LDL-c. Increases in Hmgcr and low-density lipoprotein receptor (LDLr) in the CV and RV groups could be explained by the effect of vitamin E. A reduction of LDLr in the CR group was due to the reduced dietary intake. Increases in cadherins in the CV, CR and RV groups were indicative of tissue maintenance, which was also supported by increases of α-SMA in groups CV and RV. Finally, vitamin E, with or without CR, increased Cx26, probably modulated by expression of the Hmgcr and LDLr genes. This suggests important relationship of Cxs and cholesterol metabolism genes.

Read More

Transcriptome profiling of equine vitamin E deficient neuroaxonal dystrophy identifies upregulation of liver X receptor target genes.

Finno CJ, Bordbari MH, Valberg SJ, Lee D, Herron J, Hines K, Monsour T, Scott E, Bannasch DL, Mickelson J, Xu L.

Free Radic Biol Med. 2016 Dec;101:261-271. doi: 10.1016/j.freeradbiomed.2016.10.009. Epub 2016 Oct 15.

Abstract

Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord. Differential gene expression analysis identified 157 significantly (FDR<0.05) dysregulated transcripts within the spinal cord of eNAD-affected horses. Statistical enrichment analysis identified significant downregulation of the ionotropic and metabotropic group III glutamate receptor, synaptic vesicle trafficking and cholesterol biosynthesis pathways. Gene co-expression analysis identified one module of upregulated genes significantly associated with the eNAD phenotype that included the liver X receptor (LXR) targets CYP7A1, APOE, PLTP and ABCA1. Validation of CYP7A1 and APOE dysregulation was performed in an independent biologic group and CYP7A1 was found to be additionally upregulated in the medulla oblongata of eNAD horses. Evidence of LXR activation supports a role for modulation of oxysterol-dependent LXR transcription factor activity by tocopherols. We hypothesize that the protective role of α-TOH in eNAD may reside in its ability to prevent oxysterol accumulation and subsequent activation of the LXR in order to decrease lipid peroxidation associated neurodegeneration.

Read More

Peroxisome proliferator-activated receptor γ down-regulation mediates the inhibitory effect of d-δ-tocotrienol on the differentiation of murine 3T3-F442A preadipocytes.

Torabi S, Yeganehjoo H, Shen CL, Mo H.

Nutr Res. 2016 Nov 3. pii: S0271-5317(16)30204-4. doi: 10.1016/j.nutres.2016.11.001. [Epub ahead of print]

Abstract

Tocotrienols accelerate the degradation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase that catalyzes the biosynthesis of mevalonate; the latter is essential for preadipocyte differentiation. Tocotrienols also down-regulate peroxisome proliferator-activated receptor γ (PPARγ), a key regulator of adipocyte differentiation. We hypothesized that mevalonate deprivation and PPARγ down-regulation mediate d-δ-tocotrienol-induced inhibition of adipocyte differentiation. The objectives of this study were to determine the effect of d-δ-tocotrienol on 3T3-F442A preadipocyte differentiation and the involvement of PPARγ and mevalonate. Murine 3T3-F442A preadipocytes were incubated with d-δ-tocotrienol (2.5-10 μmol/L) for 8 days. AdipoRed assay and Oil Red O staining showed that d-δ-tocotrienol dose-dependently reduced the intracellular triglyceride content. Concomitantly, d-δ-tocotrienol dose-dependently inhibited glucose uptake by 3T3-F442A cells and the expression of GLUT4, HMG CoA reductase, and p-Akt proteins. The effects of d-δ-tocotrienol on intracellular triglyceride content and glucose uptake were attenuated by rosiglitazone, an agonist of PPARγ, but not supplemental mevalonate (100 μmol/L). In contrast, mevalonate, but not rosiglitazone, reversed the effects of lovastatin, a competitive inhibitor of HMG CoA reductase shown to inhibit adipocyte differentiation via mevalonate deprivation. Trypan blue staining revealed no changes in cell viability after a 48-hour incubation of 3T3-F442A cells with d-δ-tocotrienol (0-80 μmol/L), suggesting that the adipogenesis-suppressive activity of d-δ-tocotrienol was independent of cytotoxicity. In conclusion, these findings demonstrate the antiadipogenic effect of d-δ-tocotrienol via PPARγ down-regulation.

Read More

Transcriptome profiling of equine vitamin E deficient neuroaxonal dystrophy identifies upregulation of liver X receptor target genes.

Finno CJ, Bordbari MH, Valberg SJ, Lee D, Herron J, Hines K, Monsour T, Scott E, Bannasch DL, Mickelson J, Xu L.

Free Radic Biol Med. 2016 Oct 15;101:261-271. doi: 10.1016/j.freeradbiomed.2016.10.009. [Epub ahead of print]

Abstract

Specific spontaneous heritable neurodegenerative diseases have been associated with lower serum and cerebrospinal fluid α-tocopherol (α-TOH) concentrations. Equine neuroaxonal dystrophy (eNAD) has similar histologic lesions to human ataxia with vitamin E deficiency caused by mutations in the α-TOH transfer protein gene (TTPA). Mutations in TTPA are not present with eNAD and the molecular basis remains unknown. Given the neuropathologic phenotypic similarity of the conditions, we assessed the molecular basis of eNAD by global transcriptome sequencing of the cervical spinal cord. Differential gene expression analysis identified 157 significantly (FDR<0.05) dysregulated transcripts within the spinal cord of eNAD-affected horses. Statistical enrichment analysis identified significant downregulation of the ionotropic and metabotropic group III glutamate receptor, synaptic vesicle trafficking and cholesterol biosynthesis pathways. Gene co-expression analysis identified one module of upregulated genes significantly associated with the eNAD phenotype that included the liver X receptor (LXR) targets CYP7A1, APOE, PLTP and ABCA1. Validation of CYP7A1 and APOE dysregulation was performed in an independent biologic group and CYP7A1 was found to be additionally upregulated in the medulla oblongata of eNAD horses. Evidence of LXR activation supports a role for modulation of oxysterol-dependent LXR transcription factor activity by tocopherols. We hypothesize that the protective role of α-TOH in eNAD may reside in its ability to prevent oxysterol accumulation and subsequent activation of the LXR in order to decrease lipid peroxidation associated neurodegeneration.

Read More

Tocotrienol and Its Role in Chronic Diseases.

Chin KY, Pang KL, Soelaiman IN.

Adv Exp Med Biol. 2016;928:97-130.

Abstract

Tocotrienol is a member of vitamin E family and is well-known for its antioxidant and anti-inflammatory properties. It is also a suppressor of mevalonate pathway responsible for cholesterol and prenylated protein synthesis. This review aimed to discuss the health beneficial effects of tocotrienol, specifically in preventing or treating hyperlipidaemia, diabetes mellitus, osteoporosis and cancer with respect to these properties. Evidence from in vitro, in vivo and human studies has been examined. It is revealed that tocotrienolshows promising effects in preventing or treating the health conditions previously mentioned in in vivo and in vitro models. In some cases, alpha-tocopherol attenuates the biological activity of tocotrienol. Except for its cholesterol-lowering effects, data on the health-promoting effects of tocotrienol in human are limited. As a conclusion, the encouraging results on the health beneficial effects of tocotrienol should motivate researchers to explore its potential use in human.

Read More

Page 1 of 812345...Last »