Ionization of tocopherols and tocotrienols in APCI

Bartosińska E, Borsuk-De Moor A, Siluk D, Markuszewski MJ, Wiczling P.

Rapid Commun Mass Spectrom. 2018 Mar 26. doi: 10.1002/rcm.8124

Abstract

RATIONALE:

Tocopherols and tocotrienols are chemical compounds insusceptible to the ionization process under atmospheric pressure conditions. Therefore, the selection of the optimal ion source settings for their quantification requires special attention. The aim of this study was to analyse the influence of the APCI source parameters on the response of tocochromanols and two related compounds.

METHODS:

Standard solutions of target compounds were injected on the HPLC-APCI-MS/MS system separately and analysed in 30 randomly selected ion source settings. The obtained responses were modelled by multivariate linear regression with least absolute shrinkage and selection operator. The developed models were used for choosing best APCI conditions.

RESULTS:

Multivariate linear models were built for eight tocochromanols, trolox and BHT. The APCI settings derived from the models did not increase the peak areas obtained for T and T3 during ionization process. Ionization conditions based on models for trolox and BHT improved analytical responses for 12-36% and 4-32%, respectively. The application of the ion source settings optimal for trolox and BHT to tocochromanols did not result in better analytical responses.

CONCLUSIONS:

The ionization pattern of tocochromanols in APCI source is problematic and should be further investigated. Modelling methodology for response improvement presented in this study can be applied in similar studies.

Lee H, Lim Y.

J Nutr Biochem. 2018 Mar 21;57:77-85. doi: 10.1016/j.jnutbio.2018.03.016. [Epub ahead of print]

Abstract

Chronic hyperglycemia induces impairment of muscle growth and development of diabetes mellitus (DM). Since skeletal muscle is the major site for disposal of ingested glucose, impaired glucose metabolism causes imbalance between protein synthesis and degradation which adversely affects physical mobility. In this study, we investigated the effect of tocotrienol-rich fraction (TRF) supplementation on skeletal muscle damage in diabetic mice. Diabetes was induced by a high-fat diet with streptozotocin (STZ) injection (100 mg/kg) in male C57BL/6J mice. After diabetes was induced (fasting blood glucose levels≥250 mg/dl), normal control (CON) and diabetic control (DMC) groups were administrated with olive oil, while TRF treatment groups were administrated with TRF (dissolved in olive oil) at low dose (100 mg/kg BW, LT) or high dose (300 mg/kg BW, HT) by oral gavage for 12 weeks. TRF supplementation ameliorated muscle atrophy, plasma insulin concentration and homeostatic model assessment estimated insulin resistance in diabetic mice. Moreover, TRF treatment up-regulated IRS-1 and Akt levels accompanied by increased translocation of GLUT4. Furthermore, TRF increased mitochondrial biogenesis by activating SIRT1, SIRT3 and AMPK in diabetic skeletal muscle. These changes were in part mechanistically explained by reduced levels of skeletal muscle proteins related to oxidative stress (4-hydroxynonenal, protein carbonyls, Nrf2 and HO-1), inflammation (NFkB, MCP-1, IL-6 and TNF-α), and apoptosis (Bax, Bcl₂ and caspase-3) in diabetic mice. Taken together, these results suggest that TRF might be useful as a beneficial nutraceutical to prevent skeletal muscle atrophy associated with diabetes by regulating insulin signaling via AMPK/SIRT1/PGC1α pathways in type 2 diabetic mice.

Mohamad NV, Ima-Nirwana S, Chin KY.

Drug Des Devel Ther. 2018 Mar 16;12:555-564. doi: 10.2147/DDDT.S158410. eCollection 2018.

Abstract

Background:

Patients receiving androgen deprivation therapy experience secondary hypogonadism, associated bone loss, and increased fracture risk. It has been shown that tocotrienol from Bixa orellana (annatto) prevents skeletal microstructural changes in rats experiencing primary hypogonadism. However, its potential in preventing bone loss due to androgen deprivation therapy has not been tested. This study aimed to evaluate the skeletal protective effects of annatto tocotrienol using a buserelin-induced osteoporotic rat model.

Methods:

Forty-six male Sprague Dawley rats aged 3 months were randomized into six groups. The baseline control (n=6) was sacrificed at the onset of the study. The normal control (n=8) received corn oil (the vehicle of tocotrienol) orally daily and normal saline (the vehicle of buserelin) subcutaneously daily. The buserelin control (n=8) received corn oil orally daily and subcutaneous buserelin injection (75 µg/kg) daily. The calcium control (n=8) was supplemented with 1% calcium in drinking water and daily subcutaneous buserelin injection (75 µg/kg). The remaining rats were given daily oral annatto tocotrienol at 60 mg/kg (n=8) or 100 mg/kg (n=8) plus daily subcutaneous buserelin injection (75 µg/kg) (n=8). At the end of the experiment, the rats were euthanized and their blood, tibia, and femur were harvested. Structural changes of the tibial trabecular and cortical bone were examined using X-ray micro-computed tomography. Femoral bone calcium content and biomechanical strength were also evaluated.

Results:

Annatto tocotrienol at 60 and 100 mg/kg significantly prevented the deterioration of trabecular bone and cortical thickness in buserelin-treated rats (P<0.05). Both doses of annatto tocotrienol also improved femoral biomechanical strength and bone calcium content in buserelin-treated rats (P<0.05). The effects of annatto tocotrienol were comparable to calcium supplementation.

Conclusion:

Annatto tocotrienol supplementation is effective in preventing degeneration of the bone induced by buserelin. Therefore, it is a potential antiosteoporotic agent for men receiving androgen deprivation therapy.

KEYWORDS:

androgen; fracture; gonadotropin-releasing hormone agonists; osteopenia; osteoporosis; testosterone; vitamin E

Jamilian M, Shojaei A, Samimi M, Afshar Ebrahimi F, Aghadavod E, Karamali M, Taghizadeh M, Jamilian H, Alaeinasab S, Jafarnejad S, Asemi Z

J Affect Disord. 2018 Mar 15;229:41-47. doi: 10.1016/j.jad.2017.12.049. Epub 2017 Dec 28.

Abstract

OBJECTIVE:

The aim of this study was to evaluate the effects of omega-3 and vitamin E co-supplementation on parameters of mental health and gene expression related to insulin and inflammation in subjects with polycystic ovary syndrome (PCOS).

METHODS:

Forty PCOS women were allocated into two groups and treated with 1000mg omega-3 fatty acids plus 400 IU vitamin Esupplements (n = 20) or placebo (n = 20) per day for 12 weeks. Parameters of mental health were recorded at baseline and after the 12-week intervention. Gene expression related to insulin and inflammation were measured in blood samples of PCOS women.

RESULTS:

After the 12-week intervention, compared with the placebo, omega-3 and vitamin E co-supplementation led to significant improvements in beck depression inventory total score (- 2.2 ± 2.0 vs. – 0.2 ± 1.3, P = 0.001), general health questionnaire scores (- 5.5 ± 4.6 vs. – 1.0 ± 2.3, P < 0.001) and depression anxiety and stress scale scores (- 7.2 ± 5.2 vs. – 1.3 ± 1.3, P < 0.001). Compared with the placebo, omega-3 and vitamin E co-supplementation could up-regulate peroxisome proliferator-activated receptor gamma (PPAR-γ) expression (P = 0.04) in peripheral blood mononuclear cells (PBMC) of PCOS women. In addition, compared with the placebo, omega-3 and vitamin E co-supplementation down-regulated interleukin-8 (IL-8) (P = 0.003) and tumor necrosis factor alpha (TNF-α) expression (P = 0.001) in PBMC of PCOS women. There were no significant difference between-group changes in glucose transporter 1 (GLUT-1), IL-6 and transforming growth factor beta (TGF-β) in PBMC of PCOS women.

CONCLUSION:

Omega-3 and vitamin E co-supplementation was effective in improving parameters of mental health, and gene expression of PPAR-γ, IL-8 and TNF-α of women with PCOS.

Pervez MA, Khan DA, Ijaz A, Khan S.

Turk J Gastroenterol. 2018 Mar;29(2):170-176. doi: 10.5152/tjg.2018.17297.

Abstract

BACKGROUND/AIMS:

Non-alcoholic fatty liver disease (NAFLD) is a growing public health problem worldwide and is associated with increased morbidity and mortality. Currently, there is no definitive treatment for this disease. δ-Tocotrienol has potent anti-inflammatory and antioxidant properties and may reduce liver injury in NAFLD. The present study aims to evaluate the efficacy and safety of δ-tocotrienol in the treatment of NAFLD.

MATERIALS AND METHODS:

The present study was a randomized, double-blind, placebo-controlled pilot study conducted in patients aged > 20 years, belonging to both sexes, having ultrasound-proven fatty liver disease, having a fatty liver index (FLI) of ≥ 60, and persistent elevation of alanine transaminase. A total of 71 patients were assigned to receive either oral δ-tocotrienol (n=35, 300 mg twice daily) or placebo (n=36) for 12 weeks. At the baseline and at the end of the study, clinical and biochemical parameters, including lipid profile, liver function tests, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde (MDA) were measured. Body mass index and FLI were calculated, and ultrasound grading of hepatic steatosis was performed.

RESULTS:

Out of 71 enrolled patients, 64 patients, 31 in the δ-tocotrienol group and 33 in the placebo group, completed the study. After 12 weeks of supplementation, δ-tocotrienol showed greater efficacy than placebo by decreasing serum aminotransferases, hs-CRP, MDA, and FLI score (p<0.001). However, it did not improve hepatic steatosis on ultrasound examination. No adverse effects were reported.

CONCLUSION:

δ-Tocotrienol was safe, and it effectively improved aminotransferase levels and inflammatory and oxidative stress markers in patients with NAFLD. Large-scale randomized clinical trials are warranted to further support these findings.

Abubakar IB, Lim SW, Loh HS.

Trop Life Sci Res. 2018 Mar;29(1):229-238. doi: 10.21315/tlsr2018.29.1.15. Epub 2018 Mar 2.

Abstract

Kajian terbaru mencadangkan bahawa pendekatan gabungan rawatan boleh digunakan untuk meningkatkan potensi antikanser dan menghindari batasan pemberian tocotrienol dos tinggi. Acalypha wilkesiana adalah tumbuhan ubatan yang telah digunakan sebagai rawatan tambahan untuk kanser dalam perubatan tradisional. Di sini, kesan rawatan tunggal dan gabungan β-, γ-dan δ-tocotrienols dan ekstrak etil asetat (9EA) daripada Acalypha wilkesiana pada paru-paru (A549) dan sel-sel kanser otak (U87MG) telah disiasat. γ-dan δ-tocotrienols menunjukkan kesan antiproliferatif yang lebih tinggi terhadap A549 (12.1 μg/ml dan 13.6 μg/ml) dan sel U87MG (3.3 μg/ml dan 5.2 μg/ml) berbanding β-tocotrienols (9.4 μg/ml), masing-masing. Sedangkan, 9EA merangsang kesan antiproliferatif yang kuat terhadap sel U87MG sahaja (2.0 μg/ml). Rawatan terapi tocotrienols dan 9EA mencetuskan perencatan pertumbuhan sinergis sehingga pengurangan 8.4 kali ganda dalam dos yang kuat dari β-, γ-dan δ-tocotrienols pada sel A549. Ciri-ciri apoptotik juga dibuktikan pada sel-sel A549 yang menerima rawatan tunggal dan gabungan. Sinergi ini boleh meningkatkan hasil terapeutik untuk kanser paru-paru.

Recent studies suggested that combined treatment approaches can be used to improve anticancer potency and circumvent the limitations of high-dose tocotrienols administration. Acalypha wilkesiana is a medicinal plant that has been used as an adjunct treatment for cancers in traditional medicine. Herein, the effects of single and combined treatments of β-, γ- and δ-tocotrienols and ethyl acetate extract (9EA) of Acalypha wilkesiana on lung (A549) and brain (U87MG) cancer cells were investigated. γ- and δ-tocotrienols exhibited higher potent antiproliferative effects against A549 (12.1 μg/ml and 13.6 μg/ml) and U87MG cells (3.3 μg/ml and 5.2 μg/ml) compared to β-tocotrienols (9.4 μg/ml and 92.4 μg/ml), respectively. Whereas, 9EA induced potent antiproliferative effects against U87MG cells only (2.0 μg/ml). Combined treatments of tocotrienols and 9EA induced a synergistic growth inhibition with up to 8.4-fold reduction in potent doses of β-, γ- and δ-tocotrienols on A549 cells. Apoptotic features were also evidenced on A549 cells receiving single and combined treatments. The synergism may greatly improve the therapeutic outcome for lung cancer.

KEYWORDS:

Acalypha wilkesiana; Apoptosis; Synergism; Tocotrienol

Kumar MR, Reddy GR

Hum Exp Toxicol. 2018 Mar;37(3):295-308. doi: 10.1177/0960327117698540. Epub 2017 Mar 23.

Abstract

This study was planned to determine arsenic (As) (10 mg/kg body weight given through oral gavage) induced behavioral and cholinergic perturbations in three different age groups of rats; young (postnatal day 21), adult (3 months), and aged (18 months) at 7 days post-acute exposure ( n = 6 for each of the four groups of all three age points). Further, we also evaluated the ameliorative effect of essential metal zinc (Zn; 0.02% through drinking water) and an antioxidant, α-tocopherol (vitamin E; 125 mg/kg body weight through oral gavage) against As-induced neurotoxicity. As exposure showed significant alterations in behavioral functions (open-field behavior, total locomotor activity, grip strength, exploratory behavior, and water maze learning). Cholinergic studies in three brain regions (cerebral cortex, cerebellum, and hippocampus) of different age groups also showed significant increase in acetylcholine levels and a decrease in acetylcholinesterase activity. These effects were more pronounced in hippocampus followed by cerebral cortex and cerebellum. Among the three different age points, aged animals were found to be more vulnerable to the As-induced toxicity as compared to young and adult animals suggesting that As neurotoxicity is age dependent. These As-induced alterations were significantly reversed following supplementation with Zn or vitamin E. However, vitamin E was found to elicit greater protection as compared to Zn in restoring the altered behavioral and cholinergic perturbations, providing evidence for As-induced oxidative damage.