Tocotrienol Derivatives Research Articles

A multiplex approach of MS, 1D-, and 2D-NMR metabolomics in plant ontogeny: A case study on Clusia minor L. organs (leaf, flower, fruit, and seed).

The genus Clusia L. is mostly recognised for the production of prenylated benzophenones and tocotrienol derivatives. The objective of this study was to map metabolome variation within Clusia minor organs at different developmental stages. In total 15 organs/stages (leaf, flower, fruit, and seed) were analysed by UPLC-MS and 1H- and heteronuclear multiple-bond correlation (HMBC)-NMR-based metabolomics. This work led to the assignment of 46 metabolites, belonging to organic acids(1), sugars(2) phenolic acids(1), flavonoids(3) prenylated xanthones(1) benzophenones(4) and tocotrienols(2). Multivariate data analyses explained the variability and classification of samples, highlighting chemical markers that discriminate each organ/stage. Leaves were found to be rich in 5-hydroxy-8-methyltocotrienol (8.5 μg/mg f.w.), while flowers were abundant in the polyprenylated benzophenone nemorosone with maximum level detected in the fully mature flower bud (43 μg/mg f.w.). Nemorosone and 5-hydroxy tocotrienoloic acid were isolated from FL6 for full structural characterisation. This is the first report of the NMR assignments of 5-hydroxy tocotrienoloic acid, and its maximum level was detected in the mature fruit at 50 μg/mg f.w. Seeds as typical storage organ were rich in sugars and omega-6 fatty acids. To the best of our knowledge, this is the first report on a comparative 1D-/2D-NMR approach to assess compositional differences in ontogeny studies compared with LC-MS exemplified by Clusia organs. Results derived from this study provide better understanding of the stages at which maximal production of natural compounds occur and elucidate in which developmental stages the enzymes responsible for the production of such metabolites are preferentially expressed.

Tocotrienol monomers and dimers from the roots of Litchi chinensis with tyrosinase inhibition activity

Four undescribed modified tocotrienols, including two monomers, litchinols A (1) and B (2), and two walsurol dimers, δ,δ-walsurol (3) and γ,δ-bi-O-walsurol (4), as well as seven known compounds (5–11) were isolated from the roots of Litchi chinensis. The structures of the undescribed compounds were elucidated based on analyses of spectroscopic data and ECD spectra. All tocotrienol derivatives (1–6) were evaluated for their tyrosinase inhibition activity. Only monomers 1–2 and 5–6 displayed potent inhibitory activity and greater than kojic acid. Kinetic analysis revealed that the representative compound 2 was uncompetitive inhibitor with the inhibition constant value of 5.70 μM.

Structural Elucidation of Garcipaucinones A and B From Garcinia paucinervis Using Quantum Chemical Calculations.

Two tocotrienol derivatives, garcipaucinones A (1) and B (2), and a biosynthetically related known analogue (3) were isolated from the fruit of Garcinia paucinervis. Their structures including absolute configurations were unequivocally determined by spectroscopic methods complemented with electronic circular dichroism (ECD) calculations and gauge-independent atomic orbital (GIAO) NMR calculations. Compounds 1 and 2 are the first naturally occurring tocotrienol derivatives with a 3,10-dioxatricyclo-[7.3.1.02,7]tridecane skeleton incorporating an unusual γ-pyrone motif. A reasonable biosynthetic pathway for formation of the two compounds is proposed. The antiproliferative and anti-inflammatory activities of compounds 1 and 2 were also evaluated.

Acylphloroglucinol and tocotrienol derivatives from the fruits of Garcinia paucinervis

Three undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) and three tocotrienols derivatives, named as paucinochymol A-F (1–3 and 10–12), together with six known PPAPs, were isolated from the fruits of Garcinia paucinervis. Their structures and absolute configurations were determined by extensive NMR analysis and electronic circular dichroism (ECD) calculation methods. Paucinochymol A (1) is the first compound of this type featuring a ω-isogeranyl with tetrahydrofuran unit at C-1. Paucinochymols D and E (4–5) belong to rare tocotrienol with one glorious macrocyclic and an ortho-quinone moiety, respectively. The antiproliferative and anti-inflammatory activities of all isolates were tested. Four PPAPs exhibited weak inhibitory activities against three human cancer cell lines (HepG2, T98, MCF-7) with IC50 values ranging from 10.0 to 16.0 μM. Paucinochymol D (10) displayed moderate inhibitory effects against nitric oxide (NO) production with the IC50 value of 19.8 μM.

Efficient Semi-Synthesis of Natural δ-( R)-Tocotrienols from a Renewable Vegetal Source.

Recent studies have highlighted the biological potential of tocotrienols, a vitamin E subfamily. The major natural sources of tocotrienols are complex mixtures requiring particularly challenging purification processes. The present study describes efficient semi-synthetic strategies toward relevant δ-( R)-tocotrienol derivatives, using as a starting material δ-( R)-garcinoic acid, the major vitamin E derivative isolated from Garcinia kola nuts, a renewable vegetal source.

Acylphloroglucinol and tocotrienol derivatives from the fruits of Garcinia multiflora

A new regioisomeric pair of garcimultine A (1) and B (2), and one new tocotrienol derivative garcimultine C (8) from the fruits of Garcinia multiflora showed moderate cytotoxicity on four human tumor cell lines.

A tocotrienol series with an oxidative terminal prenyl unit from Garcinia amplexicaulis

Ten tocotrienol derivatives, i.e., amplexichromanols (1–10), were isolated from stem bark of Garcinia amplexicaulis Vieill. ex Pierre collected in Caledonia. The structures of the compounds 1–5 were determined to be chromanol derivatives substituted by a polyprenyl chain oxidized in terminal position. The remaining compounds 6–10 are the corresponding dimeric derivatives. Eleven known compounds, including xanthones, tocotrienol derivatives, triterpenes and phenolic compounds, were also isolated. Their structures were mainly determined using one and two-dimensional NMR and mass spectroscopy analysis. The compounds and some amplexichromanol molecules formerly isolated from G. amplexicaulis exhibited significant antioxidant activity against lipid peroxidation and in the ORAC assay.

Abstract P3-03-11: Oxazine derivatives of g- and D- tocotrienols display potent anticancer effects in vivo

Abstract Breast cancer is a multi-stage process which leads to the accumulation of abnormal cells arising from excessive proliferation, lack of apoptosis or a combination of both. Natural compounds such as g-tocotrienol have been shown to selectively inhibit cancer cell growth without harming normal cell viability with little or no adverse side effects. The antiproliferative and apoptotic effects of the tocotrienol isoform, γ-tocotrienol, have been firmly established in various cancer types. However, in vivo studies have provided mixed results, attributed to γ-tocotrienol rapid clearance and low bioavailability. In order to improve anticancer potency and bioavailability in vivo, γ- and Δ-tocotrienol were chemically modified with electrophilic substitution reactions on their chromane ring using Mannich and Lederer-Manasse reactions, resulting in the synthesis of various oxazine derivatives. Several of these oxazine derivatives (compounds 26, 31, 39, 40 and 44) were found to display potent anticancer activity as compared to their parent compounds when tested on +SA mammary cancer cells grown in culture. These in vitro studies were followed up with in vivo studies to determine the anticancer effects of oxazine derivatives on the growth of mammary tumors in mice. Female syngeneic BALB/c mice, 4-6 week old were inoculated with 1×106 +SA mammary tumor cells in the left mammary pad. Once tumor size reached 5mm in diameter, animals were divided into different treatment groups and received an intra-tumoral injection injected of 0-120μg/20μl tocotrienol or its derivative every other day for 11 days. Afterwards, mice were sacrificed, tumors removed and placed in -80°C until further analysis. Results from these studies showed that tumor growth rate was significantly reduced in the oxazine derivative treated animals as compared to the vehicle-treated controls. Western blot analysis of tumor samples showed that the growth inhibitory effects of tocotrienol derivatives was also associated with a significant reduction in phosphorylated (activated) Akt and reductions in cell cycle regulatory proteins cyclin D1 and cyclin dependent kinases (CDK2, CDK4 and CDK6). In addition, oxazine derivative treatment was also associated with a large increase in CDK inhibitors p21 and p27, as compared to tumors obtained from the vehicle-treated control mice. Western blot analysis also showed that tumor from oxazine-derivative treated mice displayed a large reduction in NFκB levels and its downstream gene product COX-2. In summary, oxazine derivatives of tocotrienols display more potent anticancer activity both in vitro and in vivo, as compared to their parent compounds and suggest that these tocotrienol derivatives may provide some benefit as novel anticancer therapeutic agents. This work was supported, in part, by First Tec International Ltd. (Hong Kong), Malaysian Palm oil Council and the Louisiana Cancer Foundation. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-03-11.

Evaluation of γ-oryzanol content and composition from the grains of pigmented rice-germplasms by LC-DAD-ESI/MS

BackgroundRice is the staple food and one of the world’s three major grain crops. Rice contains more than 100 bioactive substances including phytic acid, isovitexin, γ-oryzanol, phytosterols, octacosanol, squalene, γ-aminobutyric acid (GABA), tocopherol, tocotrienol derivatives, etc. Out of them, γ-oryzanol is known to have important biological profile such as anti-oxidants, inhibitor of cholesterol oxidation, reduce serum cholesterol levels in animals, effective in the treatment of inflammatory diseases, inhibit tumor growth, reduce blood pressure and promotes food storage stability when used as a food additive, etc. Hence in the present investigation, we aimed to evaluate the content and composition of γ-oryzanol from pigmented rice germplasms using a liquid chromatography with diode array detection and electrospray ionization-mass spectrometry (LC-DAD-ESI/MS).FindingsIn the present study, 33 exotic pigmented rice accessions (red, white and purple) have been evaluated. Among them, the contents of γ-oryzanol varied from 3.5 to 21.0Âmg/100Âg with a mean of 11.2Âmg/100Âg. A total of ten components of γ-oryzanol including ∆7-stigmastenyl ferulate were identified of which, cycloartenyl ferulate, 24-methylenecycloartanyl ferulate, campesteryl ferulate and sitosteryl ferulate were identified as the major components. The mean proportions of steryl ferulates were in the descending order of 24-methylenecycloartanyl ferulate > cycloartenyl ferulate > campesteryl ferulate > sitosteryl ferulate > ∆7-campestenyl ferulate > campestanyl ferulate > sitostanyl ferulate > ∆7-stigmastenyl ferulate > stigamsteryl ferulate > ∆7-sitostenyl ferulate. Almost 11 accessions (33%) showed higher content than the control rice Chucheongbyeo and higher proportions ranged from 10 to 15Âmg/100Âg. Interestingly, the red rice accession Liberian Coll. B11/B-11 (21.0Âmg/100Âg) showed higher content γ-oryzanol than control rice Jeokjinjubyeo (19.1Âmg/100Âg) and the purple rice accession Padi Adong Dumarat, Mardi No.4376 (20.3Âmg/100Âg) showed a similar content with control rice Heugjinjubyeo (21.4Âmg/100Âg).ConclusionsMost of analyzed rice accessions were found to possess higher contents of γ-oryzanol than the control rice, Chucheongbyeo. In particular, the red accessions showed highest content than the white and purple accessions. The content and composition of γ-oryzanol in 33 exotic pigmented rice accessions have been evaluated and compared significantly by the present investigation.

Radical Scavenging Capacity and Antioxidant Activity of the Vitamin E Extracted from Palm Fatty Acid Distillate by Sequential Cooling Hexane

The radical scavenging capacity and antioxidant activity of the vitamin E extracted from palm fatty acid distillate by the sequential cooling hexane were compared to those of the synthetic antioxidants including butylated hydroxyanisole (BHA), 2,6-di-tert-butyl-4-methylphenol (BHT), pyrogallol (PG), tert-butylhydroquinone (TBHQ) and commercial Alpha-tocopherol. The extracted vitamin E contained 2,509.57, 9.24, 157.85, 6.70, 1,779.92, 3.97, 2,376.38, 818.80 and 7,662.45 ppm of Alpha-, Beta-, Gamma-, Delta-tocopherol and Alpha-, Beta-, Gamma-, Delta-tocotrienol, and total vitamin E, respectively. The maximum 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity of 20 ppm extracted vitamin E was 89%. The antioxidant activity determined by the methods of reducing power and ferric thiocyanate indicated that the 2.5 ppm extracted vitamin E could inhibit the oxidation of linoleic acid emulsion for more than 80% within 1 day. The superoxide scavenging activity of the extracted vitamin E was greater than those of the BHT, commercial Alpha-tocopherol, and PG, respectively. The antioxidant activity of the extracted vitamin E was 91% which was similar to those of the BHT and synthetic Alpha-tocopherol. The total-vitamin E remained 73% after heating at 190°C for 3 h. The tocopherol derivatives were more heat-stable than the tocotrienol derivatives while Gamma-tocopherol was the most heat-stable derivative. The concentration of total-vitamin E stored at 30°C for 120 days remained about 87% while the concentrations of vitamin E derivatives reduced by 2-20%.

Vitamin E: α-Tocopherol and the Other Forms of Vitamin E

Vitamin E has been a generic term for all tocopherol and tocotrienol derivatives. The most active form of vitamin E isoforms in vivo is regarded to be -tocopherol which is the only form defined as vitamin E in the US Food and Nutrition Board, causing controversy over setting dietary reference intake (DRI) of vitamin E. However, most of the countries other than the US maintain the original concept that all isoforms are accepted as vitamin E but with different biopotency. The roles of the isoforms of vitamin E other than -tocopherol have received continuous attention. Among them those of -tocopherol and -tocotrienol have been most studied in comparison with -tocopherol, since -tocopherol comprises major form of vitamin E in many plant seeds and those of the both vitamin E have been implicated in unique physiological functions. This review summarizes findings that have led a better understanding of vitamin E absorption, transport, tissue storage and various functions common and specific to vitamin E isoforms focusing - and -tocopherol as well as tocotrienols. It is expected to help redefining vitamin E and setting its DRI for Koreans.

Chemical Reactivities and Physical Effects in Comparison between Tocopherols and Tocotrienols: Physiological Significance and Prospects as Antioxidants

Vitamin E is a generic term for all tocopherol and tocotrienol derivatives. The most abundant and active form of vitamin E isoforms in vivo is alpha-tocopherol, but recently the roles of other forms of vitamin E have received renewed attention. In this review, we summarize the differences among alpha-, beta-, gamma-, delta-tocopherols and tocotrienols specifically regarding the following points; (i) their radical-scavenging efficacies and chemical reactivity with metal ions in solution, (ii) their physical effects at the liposomal membrane interior, and (iii) their protective effects against cell toxicity. Moreover, the physiological significance and future prospects for using vitamin E, especially tocotrienols, for the prevention and treatment of disease are discussed.

IUNS-AIN Nomenclature for Vitamin E

Abstract An improved new nomenclature system for the biologically and nutritionally important stereoisomers and mixtures of stereoisomers of vitamin K has been proposed. The term vitamin E is used as the generic descriptor for biologically active tocol and tocotrienol derivatives. α-Toeopherol, formerly (d-α-tocopherol, refers specifically to the isomer of trimethyltocol that occurs naturally, All-rac-α-tocopherol, formerly (dl-α-tocopherol, refers to the equimolar mixture of the 8 possible stereoisomers of α-toeopherol obtained by synthesis from racemic isophytol. 2DL-α-Tocopherol, also formerly (dl-α-tocopherol, refers to the equimolar mixture of the 2 C-2 diastereoisomers of a-tocopherol obtained by synthesis from natural phytol. 2L,-α-Tocopherol, formerly l-α-tocopherol, refers to the C-2 epimer of a-tocopherol. Both the General Assembly and the Gouncil of the International Union of Nutritional Sciences (IUNS) and the Council of the American Institute of Nutrition (AIN) have endorsed these proposals. The new IUNS-AIN nomenclature for vitamin E has been adopted as official first action. In addition the official first action method for α-tocopherol and α-tocopheryl acetate, 39.A01–39.A14, has been adopted as official final action.