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Antioxidant Potential and Angiotensin-Converting Enzyme (ACE) Inhibitory Activity of Orotic Acid-Loaded Gum Arabic Nanoparticles

Hassani A, Hussain SA, Abdullah N, Kamarudin S, Rosli R

AAPS PharmSciTech, 2019 Jan 07;20(2):53.
PMID: 30617521 DOI: 10.1208/s12249-018-1238-2

Orotic acid (OA) nanoparticles were prepared using the freeze-drying method. The antihypertensive activity and antioxidant capacity of OA and orotic acid-loaded gum arabic nanoparticles (OAGANPs) were examined using the angiotensin-converting enzyme (ACE), 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO), and β-carotene assays, as well as the quantification of total phenolic content (TPC). The DPPH and NO scavenging activities of OAGANPs were significantly higher than those of the OA solution. The β-carotene bleaching assay of OAGANPs showed a dose-dependent trend, while 500 μg/ml was significantly more effective than the other concentrations, which exerted 63.4% of the antioxidant activity. The in vitro antihypertensive assay revealed that the OAGANPs exhibited the most potent ACE inhibition activity, when compared to the OA solution. Hence, results revealed the potential of preparing the OA as a nanoparticle formulation in enhancing the antioxidant and antihypertensive properties compared to the OA solution.

Matched MeSH terms: Antioxidants/administration & dosage*
Coenzyme Q10-Loaded Fish Oil-Based Bigel System: Probing the Delivery Across Porcine Skin and Possible Interaction with Fish Oil Fatty Acids

Zulfakar MH, Chan LM, Rehman K, Wai LK, Heard CM

AAPS PharmSciTech, 2018 Apr;19(3):1116-1123.
PMID: 29181705 DOI: 10.1208/s12249-017-0923-x

Coenzyme Q10 (CoQ10) is a vitamin-like oil-soluble molecule that has anti-oxidant and anti-ageing effects. To determine the most optimal CoQ10 delivery vehicle, CoQ10 was solubilised in both water and fish oil, and formulated into hydrogel, oleogel and bigel. Permeability of CoQ10 from each formulation across porcine ear skin was then evaluated. Furthermore, the effects of the omega-3 fatty eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids from fish oil on skin permeation were investigated by means of nuclear magnetic resonance (NMR) and computerised molecular modelling docking experiments. The highest drug permeation was achieved with the bigel formulation that proved to be the most effective vehicle in delivering CoQ10 across the skin membrane due to a combination of its adhesive, viscous and lipophilic properties. Furthermore, the interactions between CoQ10 and fatty acids revealed by NMR and molecular modelling experiments likely accounted for skin permeability of CoQ10. NMR data showed dose-dependent changes in proton chemical shifts in EPA and DHA. Molecular modelling revealed complex formation and large binding energies between fatty acids and CoQ10. This study advances the knowledge about bigels as drug delivery vehicles and highlights the use of NMR and molecular docking studies for the prediction of the influence of drug-excipient relationships at the molecular level.

Matched MeSH terms: Antioxidants/administration & dosage*
Vitamin E attenuates nicotine- and noise-induced reproductive impairment in male albino Wistar rats

Bisong SA, Ukoh IE, Nna VU, Ebong PE

Andrologia, 2018 Sep;50(7):e13050.
PMID: 29806220 DOI: 10.1111/and.13050

Previous studies showed that exposure to stress or nicotine induced reproductive impairment in male rats. Here, we assessed the effect of an antioxidant (vitamin E) on nicotine-, stress- and nicotine + stress-induced reproductive impairment in male rats. Forty-eight male albino Wistar rats were divided into eight groups as follows; control, stress (generator noise 90-120 dB, 8 hr/day), nicotine (1.5 mg kg-1 day-1 ), nicotine + stress, vitamin E (100 mg kg-1 day-1 ), stress + vitamin E, nicotine + vitamin E and stress + nicotine + vitamin E. Sperm count, viability, motility and rapid progressive forward movement decreased significantly (p

Matched MeSH terms: Antioxidants/administration & dosage*
Aqueous calyxes extract of Roselle or Hibiscus sabdariffa Linn supplementation improves liver morphology in streptozotocin induced diabetic rats

Nazratun Nafizah AH, Budin SB, Zaryantey AH, Mariati AR, Santhana RL, Osman M, et al.

Arab J Gastroenterol, 2017 Mar;18(1):13-20.
PMID: 28336227 DOI: 10.1016/j.ajg.2017.02.001

BACKGROUND AND STUDY AIMS: The complex series of deleterious events among diabetes patients leads to multiple organ failure. Therefore, a holistic approach of treatment is urgently required to prevent worsening of complications. The present investigation was carried out to study the possible protective effects of Roselle or Hibiscus sabdariffa Linn (HSL) calyxes aqueous extract, as an antidiabetic and antioxidant agent against oxidative liver injury in streptozotocin-induced diabetic rats.
MATERIAL AND METHODS: A single dose of streptozotocin (45mg/kg body weight, iv) was used to induced diabetes in male Sprague Dawley rats which were then divided into two groups: Diabetic control (DC) and HSL-treated diabetic (DR) group. Normal rats were divided into normal control (NC), HSL-treated control (NR). Aqueous calyxes extract of HSL (100mg/kg/day, orally) was given for 28 consecutive days in the treated group. Weight, biochemical and histopathological (light and electron microscopic) parameters were compared in all groups.
RESULTS: Supplementation of HSL significantly lowered the level of fasting blood glucose and increased plasma insulin level in DR group compared to DC group (p<0.05). Alanine aminotransaminases and aspartate aminotransferase enzymes level were found to be significantly reduced in DR compared to DC. Microscopic examination demonstrated destruction of the liver architecture, cytoplasmic vacuolation of the hepatocytes and signs of necrosis in diabetic rats. Moreover, dilatation and congestion of blood vessels with leucocytes adherence were detected. Ultrastructural study using electron microscope showed homogeneous substance accumulation in nuclear chromatin, a decrease of organelles and mitochondrial degeneration in the diabetic rats.
CONCLUSION: Administration of HSL in diabetic rats causes significant decrease in hepatocyte destruction and prevented the changes associated with the diabetic condition. Thus, our findings provide a scientific rationale for the use of HSL as promising agent in preventing liver injury in diabetes.

Matched MeSH terms: Antioxidants/administration & dosage*
Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E

Rasool AH, Rahman AR, Yuen KH, Wong AR

Arch Pharm Res, 2008 Sep;31(9):1212-7.
PMID: 18806966 DOI: 10.1007/s12272-001-1291-5

The tocotrienol vitamin E has potent antioxidant property, however absorption is low due to high lipid solubility. A self emulsifying preparation of tocotrienol rich vitamin E (SF-TRE) had been reported to increase their bioavailability. This randomized, placebo controlled, blinded end point clinical study aimed to determine the effects of 50, 100 and 200 mg daily of SF-TRE and placebo for two months on arterial compliance and vitamin E blood levels. Assessment of arterial compliance by carotid femoral pulse wave velocity (PWV) and augmentation index (AI), plasma vitamin E, serum total cholesterol and low density lipoprotein cholesterol were taken before and after 2 months' treatment in 36 healthy males. Un-supplemented tocotrienol levels were low, after treatment, all SF-TRE treated groups had significantly higher plasma alpha, delta and delta tocotrienol concentrations compared to placebo. Augmentation index change from baseline to end of treatment for groups placebo, 50, 100, and 200 mg were 2.22+/-1.54, -6.59+/-2.84, -8.72+/-3.77, and -6.27+/-2.67% respectively (p=0.049, 0.049, and 0.047 respectively). Groups 100 and 200 mg showed significant improvement after treatment with pulse wave velocity reductions of 0.77 m/s and 0.65 m/s respectively (p=0.007 and p=0.002). There was no effect of SF-TRE on serum lipids. We conclude that there was a trend towards improvement in arterial compliance with 2 months' of SF-TRE.

Matched MeSH terms: Antioxidants/administration & dosage*
Palm fruit chemistry and nutrition

Sundram K, Sambanthamurthi R, Tan YA

Asia Pac J Clin Nutr, 2003;12(3):355-62.
PMID: 14506001

The palm fruit (Elaies guineensis) yields palm oil, a palmitic-oleic rich semi solid fat and the fat-soluble minor components, vitamin E (tocopherols, tocotrienols), carotenoids and phytosterols. A recent innovation has led to the recovery and concentration of water-soluble antioxidants from palm oil milling waste, characterized by its high content of phenolic acids and flavonoids. These natural ingredients pose both challenges and opportunities for the food and nutraceutical industries. Palm oil's rich content of saturated and monounsaturated fatty acids has actually been turned into an asset in view of current dietary recommendations aimed at zero trans content in solid fats such as margarine, shortenings and frying fats. Using palm oil in combination with other oils and fats facilitates the development of a new generation of fat products that can be tailored to meet most current dietary recommendations. The wide range of natural palm oil fractions, differing in their physico-chemical characteristics, the most notable of which is the carotenoid-rich red palm oil further assists this. Palm vitamin E (30% tocopherols, 70% tocotrienols) has been extensively researched for its nutritional and health properties, including antioxidant activities, cholesterol lowering, anti-cancer effects and protection against atherosclerosis. These are attributed largely to its tocotrienol content. A relatively new output from the oil palm fruit is the water-soluble phenolic-flavonoid-rich antioxidant complex. This has potent antioxidant properties coupled with beneficial effects against skin, breast and other cancers. Enabled by its water solubility, this is currently being tested for use as nutraceuticals and in cosmetics with potential benefits against skin aging. A further challenge would be to package all these palm ingredients into a single functional food for better nutrition and health.

Matched MeSH terms: Antioxidants/administration & dosage
Tocotrienols are needed for normal bone calcification in growing female rats

Norazlina M, Ima-Nirwana S, Abul Gapor MT, Abdul Kadir Khalid B

Asia Pac J Clin Nutr, 2002;11(3):194-9.
PMID: 12230232

In this study the effects of vitamin E deficiency and supplementation on bone calcification were determined using 4-month-old female Sprague-Dawley rats. The rats weighed between 180 and 200 g. The study was divided in three parts. In experiment I the rats were given normal rat chow (RC, control group), a vitamin E deficient (VED) diet or a 50% vitamin E deficient (50%VED) diet. In experiment 2 the rats were given VED supplemented with 30 mg/kg palm vitamin E (PVE30), 60 mg/kg palm vitamin E (PVE60) or 30 mg/kg pure alpha-tocopherol (ATF). In experiment 3 the rats were fed RC and given the same supplements as in experiment 2. The treatment lasted 8 months. Vitamin E derived from palm oil contained a mixture of ATF and tocotrienols. Rats on the VED and 50%VED diets had lower bone calcium content in the left femur compared to the RC group (91.6 +/- 13.3 mg and 118.3 +/- 26.0 mg cf 165.7 +/- 15.2 mg; P < 0.05) and L5 vertebra (28.3 +/- 4.0 mg and 39.5 +/- 6.2 mg compared with 51.4 +/- 5.8 mg; P < 0.05). Supplementing the VED group with PVE60 improved bone calcification in the left femur (133.6 +/- 5.0 mg compared with 91.6 +/- 13.3 mg; P < 0.05) and L5 vertebra (41.3 +/- 3.3 mg compared with 28.3 +/- 4.0 mg; P < 0.05) while supplementation with PVE30 improved bone calcium content in the L5 vertebra (35.6 +/- 3.1 mg compared with 28.3 +/- 4.0 mg; P < 0.05). However, supplementation with ATF did not change the lumbar and femoral bone calcium content compared to the VED group. Supplementing the RC group with PVE30, PVE60 or ATF did not cause any significant changes in bone calcium content. In conclusion, vitamin E deficiency impaired bone calcification. Supplementation with the higher dose of palm vitamin E improved bone calcium content, but supplementation with pure ATF alone did not. This effect may be attributed to the tocotrienol content of palm vitamin E. Therefore, tocotrienols play an important role in bone calcification.

Matched MeSH terms: Antioxidants/administration & dosage
Fulltext Comparative effects of a tocotrienol-rich fraction and tocopherol in aspirin-induced gastric lesions in rats

Nafeeza MI, Fauzee AM, Kamsiah J, Gapor MT

Asia Pac J Clin Nutr, 2002;11(4):309-13.
PMID: 12495264

This study examined the effects of a tocotrienol-rich fraction (TRF) obtained from palm oil on the healing of aspirin-induced gastric mucosal lesions. Thirty-six male Sprague-Dawley rats (200-250 g) were randomly divided into three groups. Group I was fed a vitamin E-deficient diet (control), Group II was fed a vitamin E-deficient diet supplemented with tocopherol (300 mg/kg food) and Group III was fed a vitamin E-deficient diet supplemented with TRF (300 mg/kg food). After eight weeks, the control and treated groups received a single intragastric dose of 400 mg/kg body weight aspirin. The rats were killed 24 h after exposure to aspirin. Assessment of gastric lesions showed a lower gastric lesion index in the TRF (P = 0.0005) and tocopherol groups (P = 0.0008) compared to the control. The gastric malondialdehyde (MDA) content was also lower in the TRF (P = 0.025) and tocopherol groups (P = 0.025) compared to control. There were, however, no significant differences in the gastric lesion index and gastric MDA content between the TRF and tocopherol-fed groups. There were no significant differences in the adherent gastric mucous concentration and gastric acid concentration among all groups. We conclude that the TRF and tocopherol are equally effective in preventing aspirin-induced gastric lesions. The most probable mechanism is through their ability to limit lipid peroxidation, which is involved in aspirin-induced gastric lesions.

Matched MeSH terms: Antioxidants/administration & dosage*
Effect of vitamin E on plasma malondialdehyde, antioxidant enzyme levels and the rates of wound closures during wound healing in normal and diabetic rats

Musalmah M, Fairuz AH, Gapor MT, Ngah WZ

Asia Pac J Clin Nutr, 2002;11 Suppl 7:S448-51.
PMID: 12492633

Vitamin E is composed of various subfamilies that include tocopherols and tocotrienols. These compounds have antioxidant properties but differ in structure, dietary source and potency. In this study we evaluated the efficacy of alpha-tocopherol as an antioxidant and its role in wound closure in normal and streptozotocin-induced diabetic rats. The healing of 6 cm linear incisions created on the back of each male Sprague-Dawley rat (250-300 g) was monitored by measuring the length of the wounds daily. The rats were divided into two categories; normal and streptozotocin-induced diabetic rats. For each category, the animals were further divided into two groups; those untreated and those receiving 200 mg/kg bodyweight alpha-tocopherols daily by oral gavage. All rats were fed standard food and water ad libitum. Blood samples were taken at 0, 5 and 10 days after the wounds were created for the determination of malondialdehyde levels and red cell superoxide dismutase, catalase and glutathione peroxidase activities. The results showed that alpha-tocopherol reduced plasma malondialdehyde levels, increased glutathione peroxidase activity and accelerated the rate of wound closure in treated rats.

Matched MeSH terms: Antioxidants/administration & dosage
Vitamin E in cardiovascular disease: has the die been cast?

Yusoff K

Asia Pac J Clin Nutr, 2002;11 Suppl 7:S443-7.
PMID: 12492632

Cardiovascular disease, in particular coronary artery disease (CAD), remains the most important cause of morbidity and mortality in developed countries and, in the near future, more so in the developing world. Atherosclerotic plaque formation is the underlying basis for CAD. Growth of the plaque leads to coronary stenosis, causing a progressive decrease in blood flow that results in angina pectoris. Acute myocardial infarction and unstable angina were recently recognised as related to plaque rupture, not progressive coronary stenosis. Acute thrombus formation causes an abrupt coronary occlusion. The characteristics of the fibrin cap, contents of the plaque, rheological factors and active inflammation within the plaque contribute to plaque rupture. Oxidative processes are important in plaque formation. Oxidized low density lipoproteins (LDL) but not unoxidized LDL is engulfed by resident intimal macrophages, transforming them into foam cells which develop into fatty streaks, the precursors of the atherosclerotic plaque. Inflammation is important both in plaque formation and rupture. Animal studies have shown that antioxidants reduce plaque formation and lead to plaque stabilisation. In humans, high intakes of antioxidants are associated with lower incidence of CAD, despite high serum cholesterol levels. This observation suggests a role for inflammation in CAD and that reducing inflammation using antioxidants may ameliorate these processes. Men and women with high intakes of vitamin E were found to have less CAD. Vitamin E supplementation was associated with a significant reduction in myocardial infarction and cardiovascular events in the incidence of recurrent myocardial infarction. In the hierarchy of evidence in evidence-based medicine, data from large placebo-controlled clinical trials is considered necessary. Results from various mega-trials have not shown benefits (nor adverse effects) conferred by vitamin E supplementation, suggesting that vitamin E has no role in the treatment of CAD. These results do not seem to confirm, at the clinical level, the effect of antioxidants against active inflammation during plaque rupture. However, a closer examination of these studies showed a number of limitations, rendering them inconclusive in addressing the role of vitamin E in CAD prevention and treatment. Further studies that specifically address the issue of vitamin E in the pathogenesis of atherosclerosis and in the treatment of CAD need be performed. These studies should use the more potent antioxidant property of alpha-tocotrienol vitamin E.

Matched MeSH terms: Antioxidants/administration & dosage
Fulltext Antioxidant intake and status, and oxidative stress in relation to breast cancer risk: a case-control study

Sharhar S, Normah H, Fatimah A, Fadilah RN, Rohi GA, Amin I, et al.

Asian Pac J Cancer Prev, 2008 Apr-Jun;9(2):343-49.
PMID: 18712988

A case control study was carried out to investigate associations between breast cancer risk, antioxidant status and oxidative stress among women in Klang Valley and Selangor. A total of 57 newly diagnosed cases aged 30 to 66 years old participated and were matched for age and ethnicity with 139 controls with no diagnosis of cancer or other chronic diseases. An interview based questionnaire designed to collect information on demographic and socioeconomic status, as well as reproductive, medical and dietary history was used. Anthropometric measurements including weight, height, waist and hip circumference were made and a 10 ml fasting venous blood sample was taken for glucose testing and analysis of plasma vitamin antioxidants and malondialdehyde. Hair and toenail samples were taken for selenium analysis. Results showed that the mean intake of vitamin A, vitamin E and selenium among cases (606.8 +/- 334.8 microg/d, 6.1 +/- 2.4 g/d, 56.9 +/- 16.2 microg/d) was lower than controls (724.7 +/- 414 microg/day, 6.9 +/- 3.0 g/d, 60.8 +/- 17.5 microg/d, respectively) (p<0.05 for all parameters). A similar trend was noted for plasma vitamin A and E and also selenium in hair and toenails. Poor antioxidant status as indicated by low plasma vitamin A (<284.3 microg/l or <366.3 microg/l) increased risk of breast cancer by approximately two fold, whilst low plasma vitamin E (<2.5 mg/dl, <2.8 mg/dl and <3.1 mg/dl) increased the risk by two to three fold [Adjusted OR 2.97 (95% CI 1.38-3.48), 2.32 (95% CI 1.07-2.41) and 2.12 (95% CI 1.00-4.21)]. Cases had a greater level of malondialdehyde 4.4 +/- 1.1 mmol/g protein), an indicator of oxidative stress, as compared to controls (3.2 +/- 1.7 mmol/g protein) (p<0.05). A high level of MDA (> or = 4.8 mmol/g protein) was associated with breast cancer [Adjusted OR 6.82 (95% CI 1.95-23.9)]. It is concluded that a poor antioxidant status and high oxidative stress are associated with breast cancer risk. Thus, it is essential for Malaysian women to obtain a good antioxidant status by consuming a diet rich in vitamins A and E as well as selenium and adopt healthy behaviour to reduce oxidative stress in order to prevent breast cancer.

Matched MeSH terms: Antioxidants/administration & dosage*
Clinical Efficacy of a Mouth-Exercising Device Adjunct to Local Ointment Intra-Lesional Injections and Surgical Treatment for Oral Submucous Fibrosis: a Randomized Controlled Trial

Patil P, Hazarey V, Chaudhari R, Nimbalkar-Patil S

Asian Pac J Cancer Prev, 2016;17(3):1255-9.
PMID: 27039756

BACKGROUND: Oral physiotherapy or mouth exercise is considered to be an adjunct but mandatory treatment modality for oral submucous fibrosis (OSMF). This study planned to evaluate the clinical efficacy of a newly designed mouth exercising device (MED) in OSMF patients receiving local ointment, intra-lesional drugs and surgical treatment.
MATERIALS AND METHODS: A total of 231 OSMF patients were selected and treated with basic regime including topical corticosteroids, oral antioxidants and the icecream-stick exercise regime and allotted randomly to two equal groups A and B. Group-A patients were additionally given MED. Subgroups A1 and B1 patients with an inter-incisal distance (IID) 20-35mm were not given any additional therapy; subgroup A2 and B2 patients (IID 20-35mm) were treated additionally with intra-lesional injections. Subgroups A3 and B3 with IID<20mm were managed surgically. IID was measured at baseline and at 6 months recall. The change in IID measurements was calculated and statistically analyzed using 2-way ANOVA and Tukeys multiple post hoc analysis.
RESULTS: Average improvement in IID after six months of recall visits was observed to be 8.4 mm in subgroup-A1 (n-53) compared to 5.5 mm in B1(n-50) (p<0.01). The IID improvement in subgroup-A2 was found to be 9.3mm (n-46) compared to 5.1 mm in B2 (n-48) (p<0.01). In the surgery group, mouth opening improvement was observed to be 9.6 mm in subgroup A3 (n-18) compared to 4.8 mm for B3 (n-16) (p<0.01).
CONCLUSIONS: Use of the MED appears to be effective for increasing oral opening in OMSF patients in conjunction with local, injection and/or surgical treatment.

Matched MeSH terms: Antioxidants/administration & dosage*
Fulltext Chlorophytum borivilianum (Safed Musli) root extract prevents impairment in characteristics and elevation of oxidative stress in sperm of streptozotocin-induced adult male diabetic Wistar rats

Giribabu N, Kumar KE, Rekha SS, Muniandy S, Salleh N

BMC Complement Altern Med, 2014;14:291.
PMID: 25104050 DOI: 10.1186/1472-6882-14-291

We hypothesized that C. borivilianum root, known to improve male reproductive performance, prevents impairment in characteristics, morphology and elevation of oxidative stress in sperm of diabetics. We therefore investigated the effect of aqueous root extract of C. borivilianum on these parameters in diabetic rat model.

Matched MeSH terms: Antioxidants/administration & dosage
Fulltext Effect of oral administration of ethanolic extract of Vitex negundo on thioacetamide-induced nephrotoxicity in rats

Kadir FA, Kassim NM, Abdulla MA, Yehye WA

BMC Complement Altern Med, 2013 Oct 30;13:294.
PMID: 24499255 DOI: 10.1186/1472-6882-13-294

BACKGROUND: Oxidative stress due to abnormal induction of reactive oxygen species (ROS) molecules is believed to be involved in the etiology of many diseases. Evidences suggest that ROS is involved in nephrotoxicity through frequent exposure to industrial toxic agents such as thioacetamide (TAA). The current investigation was designed to explore the possible protective effects of the leaves of Vitex negundo(VN) extract against TAA-induced nephrotoxicity in rats.
METHODS: Twenty four Sprague Dawleyrats were divided into four groups: (A) Normal control, (B) TAA (0.03% w/v in drinking water), (C) VN100 (VN 100 mg/kg + TAA) and (D) VN300 (VN 300 mg/kg + TAA). Blood urea and serum creatinine levels were measured,supraoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels of renal tissue were assayed. Histopathological analysis together with the oxidative stress nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22phox in kidney sections were examined in all experimental groups.
RESULTS: Blood urea and serum creatinine levels were increased in TAA group as a result of the nephrotoxicity compared to the VN100 and VN300 groups where, the levels were significantly decreased (p

Matched MeSH terms: Antioxidants/administration & dosage
Fulltext Safety and efficacy of tocotrienol supplementation for bone health in postmenopausal women: protocol for a dose-response double-blinded placebo-controlled randomised trial

Shen CL, Mo H, Yang S, Wang S, Felton CK, Tomison MD, et al.

BMJ Open, 2016 12 23;6(12):e012572.
PMID: 28011809 DOI: 10.1136/bmjopen-2016-012572

INTRODUCTION: Osteoporosis is a major health concern in postmenopausal women, and oxidative stress contributes to the development of bone loss. Cellular studies and ovariectomised rat model mimicking bone loss in postmenopausal women show the bone-protective effect of tocotrienols (TTs) with antioxidant capability. We aim to access the safety and efficacy of TT consumption for bone health in postmenopausal women.
METHODS AND ANALYSIS: In this 12-week randomised double-blinded placebo-controlled trial for the effects of dietary TT supplementation in postmenopausal women, postmenopausal women aged 45 years and older with at least 1 year after menopause and bone mineral density T-score at the spine and/or hip 2.5 or more below the reference values will be randomly assigned to 3 daily supplements: (1) placebo group receiving 860 mg olive oil, (2) low TT group receiving 430 mg of 70% pure TTs (containing 300 mg TT) and (3) high TT group receiving 860 mg of 70% pure TTs (600 mg TT). The primary outcome measure will be urinary N-terminal telopeptide. The secondary outcome measures will be serum bone-specific alkaline phosphatase, receptor activator of nuclear factor-κB ligand, osteoprotegerin, urinary 8-hydroxy-2'-deoxyguanosine and quality of life. At 0, 6 and 12 weeks, the following will be assessed: (1) primary and secondary outcome measures; (2) serum TT and tocopherol concentrations; (3) physical activity and food frequency questionnaires. Liver function will be monitored every 6 weeks for safety. 'Intent-to-treat' principle will be employed for data analysis. A model of repeated measurements with random effect error terms will be applied. Analysis of covariance, χ2 analysis and regression will be used for comparisons.
ETHICS AND DISSEMINATION: This study was approved by the Bioethics Committee of the Texas Tech University Health Sciences Center. The findings of this trial will be submitted to a peer-reviewed journal in the areas of bone or nutrition and international conferences.
TRIAL REGISTRATION NUMBER: NCT02058420; results.

Matched MeSH terms: Antioxidants/administration & dosage
Fulltext Palm tocotrienol exerted better antioxidant activities in bone than alpha-tocopherol

Maniam S, Mohamed N, Shuid AN, Soelaiman IN

Basic Clin Pharmacol Toxicol, 2008 Jul;103(1):55-60.
PMID: 18598299 DOI: 10.1111/j.1742-7843.2008.00241.x

The aim of this study was to investigate the effects of vitamin E on the levels of lipid peroxidation and antioxidant enzymes in rat bones. Fifty-six normal male Sprague-Dawley rats, aged 3 months, were randomly divided into seven groups with eight rats in each group. The age-matched control group was given the vehicle olive oil, by oral gavage daily. Six of the treatment groups received either palm tocotrienol or pure alpha-tocopherol at the dose of 30, 60 or 100 mg/kg body weight, by oral gavage daily, 6 days a week for 4 months. Thiobarbituric acid-reactive substance (TBARS) that is an index to measure the level of lipid peroxidation and the antioxidant enzymes, glutathione peroxidase and superoxide dismutase levels were measured in the femur at the end of the study. Palm tocotrienol at the dose of 100 mg/kg body weight significantly reduced the TBARS level in the femur with a significant increase in glutathione peroxidase activity compared to the age-matched control group. These were not observed in the alpha-tocopherol groups. Palm tocotrienol was more effective than pure alpha-tocopherol acetate in suppressing lipid peroxidation in bone. Palm tocotrienol showed better protective effect against free radical damage in the femur compared to alpha-tocopherol. This study suggests that palm tocotrienol plays an important role in preventing imbalance in bone metabolism due to free radicals.

Matched MeSH terms: Antioxidants/administration & dosage
Boldine suppresses dextran sulfate sodium-induced mouse experimental colitis: NF-κB and IL-6/STAT3 as potential targets

Pandurangan AK, Mohebali N, Hasanpourghadi M, Looi CY, Mustafa MR, Mohd Esa N

Biofactors, 2016 May;42(3):247-58.
PMID: 26891685 DOI: 10.1002/biof.1267

Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration, and upregulation of inflammatory mediators. Boldine is an alkaloid compound found in Boldo tree, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumor, and immunomodulatory activities. Hence, the effect of boldine for its anti-inflammatory properties against dextran sulfate sodium (DSS)-induced UC in BALB/c mice was studied. Administration of boldine to DSS-induced mice protects colon damage by reduced disease activity index, spleen weight, and increased colon length. Also administration of boldine showed a reduction in the activity of myeloperoxidase (MPO) and CD 68+ expression. Boldine reduced the colon damage, with significant reductions in both the extent and the severity of the inflammation as well as in crypt damage and leukocyte infiltration in the mucosa. Analysis in vivo showed clear decrease in the production of tumor necrosis factor (TNF)-α, Interleukin (IL)-6, IL-17, and signal transducer and activator of transcription-(p-STAT3)(Y705) with nuclear factor (p65-NF-κB) production being reduced significantly. Moreover, p65-NF-κB activation was reduced in mouse macrophage RAW 264.7 cells in vitro. The data demonstrated that boldine may be beneficial in colitis through selective immunomodulatory effects, which may be mediated, at least in part, by inhibition of p65-NF-κB and STAT3 signaling pathways. © 2016 BioFactors, 42(3):247-258, 2016.

Matched MeSH terms: Antioxidants/administration & dosage
Fulltext Biomedical properties of a natural dietary plant metabolite, zerumbone, in cancer therapy and chemoprevention trials

Rahman HS, Rasedee A, Yeap SK, Othman HH, Chartrand MS, Namvar F, et al.

Biomed Res Int, 2014;2014:920742.
PMID: 25025076 DOI: 10.1155/2014/920742

Zerumbone (ZER) is a naturally occurring dietary compound, present in many natural foods consumed today. The compound derived from several plant species of the Zingiberaceae family that has been found to possess multiple biomedical properties, such as antiproliferative, antioxidant, anti-inflammatory, and anticancer activities. However, evidence of efficacy is sparse, pointing to the need for a more systematic review for assessing scientific evidence to support therapeutic claims made for ZER and to identify future research needs. This review provides an updated overview of in vitro and in vivo investigations of ZER, its cancer chemopreventive properties, and mechanisms of action. Therapeutic effects of ZER were found to be scientifically plausible and could be explained partially by in vivo and in vitro pharmacological activities. Much of the research outlined in this paper will serve as a foundation to explain ZER anticancer bioactivity, which will open the door for the development of strategies in the treatment of malignancies using ZER.

Matched MeSH terms: Antioxidants/administration & dosage
Fulltext Apoptosis Induction by Polygonum minus is related to antioxidant capacity, alterations in expression of apoptotic-related genes, and S-phase cell cycle arrest in HepG2 cell line

Mohd Ghazali MA, Al-Naqeb G, Krishnan Selvarajan K, Hazizul Hasan M, Adam A

Biomed Res Int, 2014;2014:539607.
PMID: 24955361 DOI: 10.1155/2014/539607

Polygonum minus (Polygonaceae) is a medicinal herb distributed throughout eastern Asia. The present study investigated antiproliferative effect of P. minus and its possible mechanisms. Four extracts (petroleum ether, methanol, ethyl acetate, and water) were prepared by cold maceration. Extracts were subjected to phytochemical screening, antioxidant, and antiproliferative assays; the most bioactive was fractionated using vacuum liquid chromatography into seven fractions (F1-F7). Antioxidant activity was measured via total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Antiproliferative activity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Most active fraction was tested for apoptosis induction and cell cycle arrest in HepG2 cells using flow cytometry and confocal microscopy. Apoptotic-related gene expression was studied by RT-PCR. Ethyl acetate extract was bioactive in initial assays. Its fraction, F7, exhibited highest antioxidant capacity (TPC; 113.16 ± 6.2 mg GAE/g extract, DPPH; EC50: 30.5 ± 3.2 μg/mL, FRAP; 1169 ± 20.3 μmol Fe (II)/mg extract) and selective antiproliferative effect (IC50: 25.75 ± 1.5 μg/mL). F7 induced apoptosis in concentration- and time-dependent manner and caused cell cycle arrest at S-phase. Upregulation of proapoptotic genes (Bax, p53, and caspase-3) and downregulation of antiapoptotic gene, Bcl-2, were observed. In conclusion, F7 was antiproliferative to HepG2 cells by inducing apoptosis, cell cycle arrest, and via antioxidative effects.

Matched MeSH terms: Antioxidants/administration & dosage
Fulltext Effects of Tamarindus indica fruit pulp extract on abundance of HepG2 cell lysate proteins and their possible consequential impact on metabolism and inflammation

Chong UR, Abdul-Rahman PS, Abdul-Aziz A, Hashim OH, Mat-Junit S

Biomed Res Int, 2013;2013:459017.
PMID: 24455694 DOI: 10.1155/2013/459017

The fruit pulp extract of Tamarindus indica has been reported for its antioxidant and hypolipidemic properties. In this study, the methanol extract of T. indica fruit pulp was investigated for its effects on the abundance of HepG2 cell lysate proteins. Cell lysate was extracted from HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp. Approximately 2500 spots were resolved using two-dimensional gel electrophoresis and the abundance of 20 cellular proteins was found to be significantly reduced. Among the proteins of reduced abundance, fourteen, including six proteins involved in metabolism (including ethanolamine phosphate cytidylyltransferase), four mitochondrial proteins (including prohibitin and respiratory chain proteins), and four proteins involved in translation and splicing, were positively identified by mass spectrometry and database search. The identified HepG2 altered abundance proteins, when taken together and analyzed by Ingenuity Pathways Analysis (IPA) software, are suggestive of the effects of T. indica fruit pulp extract on metabolism and inflammation, which are modulated by LXR/RXR. In conclusion, the methanol fruit pulp extract of T. indica was shown to cause reduced abundance of HepG2 mitochondrial, metabolic, and regulatory proteins involved in oxidative phosphorylation, protein synthesis, and cellular metabolism.

Matched MeSH terms: Antioxidants/administration & dosage*

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