Configuration of the vitamin E analogue garcinoic acid extracted from Garcinia Kola seeds.
ABSTRACT Vitamin E derivatives bearing a carboxylic group have recently gained great attention because of their antitumoral properties. Garcinoic acid (trans-13'-carboxy-delta-tocotrienol) is a vitamin E analog extracted from Garcinia Kola seeds in which the carboxylic group is at the end of the aliphatic side chain and reported to be a racemate based on the optical rotation measurements. However, CD determination of a sample of the acid analyzed by us gave a positive peak at 208 nm, indicating that it is not a racemate. To assess the enantiomeric composition of garcinoic acid, it was thus transformed to alpha-tocopherol and analyzed by chiral HPLC on column OD-H. On the basis of the elution order of alpha-tocopherol stereoisomers, the garcinoic acid sample resulted to be enantiopure with R configuration at carbon 2 of the chroman ring. Moreover, in a preliminary test, the acid and some of its derivatives showed a marked antiproliferative effect on glioma C6 cancer cells.
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ABSTRACT: Although the metabolism of vitamin E has been extensively studied in cell culture, animals, and humans, biochemical analyses of intermediate metabolites are scarce. We here describe the synthesis and proapoptotic properties of long-chain metabolites of α- and δ-tocopherol. Several long-chain vitamin E metabolites, namely 13'-hydroxy- and 13'-carboxychromanols, were synthesized from garcinoic acid, a δ-tocotrienol derivative extracted from the African bitter nut Garcinia kola. Both α- and δ-13'-carboxychromanol induced cell death in HepG2 cells at EC(50) of 13.5 and 6.5 μM, respectively. Apoptosis was quantified by annexin V/7-AAD staining and flow cytometry analysis. By immunoblot analyses, we observed activation of both caspase-3 and caspase-9 as well as PARP-1 cleavage. Parameters of mitochondrial dysfunction including reduced mitochondrial membrane potential and increased intracellular and intramitochondrial reactive oxygen species formation were observed after metabolite treatment. Last, long-chain hydroxychromanols were readily metabolized to the corresponding carboxychromanols in HepG2 cells. Taken together, these results indicate that long-chain metabolites may be responsible for antiproliferative properties of vitamin E vitamers.Free Radical Biology and Medicine 11/2010; 49(8):1315-22. DOI:10.1016/j.freeradbiomed.2010.07.024 · 5.71 Impact Factor
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ABSTRACT: Context: In Africa, Garcinia kola Heckel (Guttiferae) seed is commonly recommended in folklore medicine for the treatment of diabetes and its associated complications. Objective: The present study evaluated this traditional claim by mechanistic investigation into the effect of G. kola seed administration on renal, hepatic, and testicular oxidative damage in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Diabetes mellitus was induced in adult male Wistar rats by an intraperitoneal injection of STZ (50 mg/kg). The diabetic rats were thereafter treated orally once per day with G. kola seed (250 mg/kg) and monitored for 14 d. Clinical observations, plasma biochemistry, hormonal profile, oxidative stress indices, sperm characteristics, and histopathological examination of the kidney, liver, and testes were evaluated to monitor treatment-related effects of G. kola seed in STZ-induced diabetic rats. Results and discussion: Garcinia kola seed administration significantly ameliorated hyperglycemia mediated damage by decreasing the blood glucose level (72.8% and 84.6% on the 7th and 14th post-treatment days, respectively), enhancement of the antioxidant system, inhibition of lipid peroxidation, and improving the architecture of the kidney, liver, and testes in STZ-induced diabetic rats. In addition, G. kola seed intervention restored the kidney and liver function biomarkers, the sperm characteristics as well as the plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, triiodothyronine (T3), and thyroxine (T4) to normal in STZ-induced diabetic rats. Conclusion: The findings from this investigation provide persuasive scientific support for the traditional use of G. kola seed in the treatment of diabetes and its associated complications.Pharmaceutical Biology 09/2014; 53(5). DOI:10.3109/13880209.2014.937504 · 1.34 Impact Factor
- ChemMedChem 04/2010; 5(4):540-3. DOI:10.1002/cmdc.200900492 · 3.05 Impact Factor