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Nutrients Jul 2022Phytoene (PT) and phytofluene (PTF) are colourless carotenoids presents in the human diet and in blood, faeces and tissues and are biologically active. However, there is...
Phytoene (PT) and phytofluene (PTF) are colourless carotenoids presents in the human diet and in blood, faeces and tissues and are biologically active. However, there is very little data on these carotenoids. This study aims to assess PT and PTF concentrations in serum from healthy Spanish normolipemic subjects ( = 101, 45-65 years) and the effect of a fruit and vegetable dietary intervention (4 weeks, = 29) on PT and PTF concentration in serum and faeces and dietary intake. Serum and faecal concentrations were analysed by HPLC and dietary intake by 3 × 24 h recalls. PT showed higher concentrations than PTF in serum, faeces and in the dietary intake. Considering both studies, PT and PTF concentrations in serum were 0.16 ± 0.07 and 0.05 ± 0.04 µmol/L, respectively, in faeces 17.7 ± 20.3 and 6.5 ± 7.9 µg/g, respectively, and in dietary intake the median was 2.4 and 0.6 mg/p/day, respectively. Carrots and tomatoes were the major dietary contributors of these carotenoids. The dietary intervention did not cause significant variations in the PT and PTF intake or serum concentrations, but a lower concentration in faeces was observed for the fruit group (PT: = 0.024; PTF isomer-3: = 0.034). These data highlight the need for further research on the activities of these carotenoids in humans.
Topics: Adult; Carotenoids; Diet; Eating; Fruit; Humans; Lutein; Vegetables
PubMed: 35889879
DOI: 10.3390/nu14142922 -
Accounts of Chemical Research Apr 2020From structure elucidation and biogenesis to synthetic methodology and total synthesis, terpene natural products have profoundly influenced the development of organic... (Review)
Review
From structure elucidation and biogenesis to synthetic methodology and total synthesis, terpene natural products have profoundly influenced the development of organic chemistry. Moreover, their myriad functional attributes range from fragrance to pharmaceuticals and have had great societal impact. Ruzicka's formulation of the "biogenetic isoprene rule," a Nobel Prize winning discovery now over 80 years old, allowed for identification of higher order terpene (aka "isoprenoid") structures from simple five-carbon isoprene fragments. Notably, the isoprene rule still holds pedagogical value to students of organic chemistry today. Our laboratory has completed syntheses of over two dozen terpene and meroterpene structures to date, and the isoprene rule has served as a key pattern recognition tool for our synthetic planning purposes. At the strategic level, great opportunity exists in finding unique and synthetically simplifying ways to connect the formal C isoprene fragments embedded in terpenes. Biomimetic cationic polyene cyclizations represent the earliest incarnation of this idea, which has facilitated expedient routes to certain terpene polycycle classes. Nonetheless, a large swath of terpene chemical space remains inaccessible using this approach.In this Account, we describe strategic insight into our endeavors in terpene synthesis published over the last five years. We show how biosynthetic understanding, combined with a desire to utilize abundant and inexpensive [C] building blocks, has led to efficient, abiotic syntheses of multiple complex terpenes with disparate ring systems. Informed by nature, but unconstrained by its processes, our synthetic assembly exploits chemical reactivity across diverse reaction types-including radical, anionic, pericyclic, and metal-mediated transformations.First, we detail an eight-step synthesis of the cembrane diterpene chatancin from dihydrofarnesal using a bioinspired-but not -mimetic-cycloaddition. Next, we describe the assembly of the antimalarial cardamom peroxide using a polyoxygenation cascade to fuse multiple units of molecular oxygen onto a dimeric skeleton. This three-to-four-step synthesis arises from (-)-myrtenal, an inexpensive pinene oxidation product. We then show how a radical cyclization cascade can forge the hallmark cyclooctane ring system of the complex sesterterpene 6--ophiobolin N from two simple polyprenyl precursors, (-)-linalool and farnesol. To access the related, more complex metabolite 6-ophiobolin A, we exploited the plasticity of our synthetic route and found that use of geraniol (C) rather than farnesol (C) gave us the flexibility needed to address the additional oxidation found in this congener. Following this work, we describe two strategies to access several guaianolide sesquiterpenes. Retrosynthetic disconnection to monoterpenes, carvone or (-)-linalool, coupled with a powerful allylation strategy allowed us to address guaianolides with disparate stereochemical motifs. Finally, we examine a semisynthetic approach to the sesquiterpenes from the abundant 15-carbon feedstock terpene (+)-cedrol using an abiotic ring shift and multiple C-H oxidation reactions inspired by a postulated biosynthesis of this natural product class.
Topics: Chemistry Techniques, Synthetic; Neoprene; Terpenes
PubMed: 32202757
DOI: 10.1021/acs.accounts.0c00055 -
Food and Chemical Toxicology : An... Oct 2022Spontaneous oxidation of β-carotene yields a polymer-rich product (OxBC) together with minor amounts of many apocarotenoids. OxBC's activity extends β-carotene's...
Spontaneous oxidation of β-carotene yields a polymer-rich product (OxBC) together with minor amounts of many apocarotenoids. OxBC's activity extends β-carotene's benefits beyond vitamin A, finding utility in supporting health in livestock, pets, and humans. Although the naturally occurring form of OxBC is consumed in foods and feeds, a direct demonstration of synthetic OxBC's safety provides additional support for its usage. A toxicological study in rats showed a maximum tolerated single oral dose of 5000 mg/kg, an LD of more than 10,000 mg/kg, and a NOAEL of 1875 mg/kg body weight. A repeat-dose 90-day oral toxicity study showed no adverse physiological or pathological effects. A study of OxBC uptake by mice over 2-5 days showed OxBC already was naturally present. The highest levels were in liver, lung, and hamstring. Dosing did not increase levels in liver, kidney, lung, and muscle. Increases occurred in urine, intestinal content, plasma, feces, spleen, and cecum with preferential elimination of polymer, consistent with processing of OxBC. Compared to the 4:1 polymer: apocarotenoid ratio of OxBC, polymer was enriched in liver and spleen and depleted in lung, kidney, hamstring, and abdominal muscle. The apparent control of OxBC in major tissues further supports its safety.
Topics: Animals; Biological Transport; Humans; Liver; Mice; Polymers; Rats; Vitamin A; beta Carotene
PubMed: 36041660
DOI: 10.1016/j.fct.2022.113387 -
Radiology. Imaging Cancer Jul 2022
Topics: Embolization, Therapeutic; Polyvinyls; Vascular Surgical Procedures
PubMed: 35838533
DOI: 10.1148/rycan.229012 -
Biomedicine & Pharmacotherapy =... May 2023The potent relation between lycopene intake and reduced incidence of a variety of cancers has an increasing interest. This comprehensive review aims to highlight the in... (Review)
Review
The potent relation between lycopene intake and reduced incidence of a variety of cancers has an increasing interest. This comprehensive review aims to highlight the in vivo and in vitro research evaluating the anticancer mechanisms of lycopene by underlining the experiment conditions. In addition to these, the general characterization of lycopene has been explained. A collection of relevant scientific pharmacological articles from the following databases PubMed/MedLine, Web of Science, Scopus, TRIP database, and Google Scholar on the mechanisms of anticancer molecular action and cellular effects of lycopene in various types of tumors was performed. The anticancer potential of lycopene has been described by various in vitro cells, animal studies, and some clinical trials. It has been revealed that the anticancer potential of lycopene is mainly due to its powerful singlet-oxygen quencher characteristics, simulation of detoxifying/antioxidant enzymes production, initiation of apoptosis, inhibition of cell proliferation and cell cycle progression as well as modulations of gap junctional communication, the growth factors, and signal transduction pathways. It has been highlighted that the anticancer properties of lycopene are primarily linked to factors including; dose, presence of drug delivery systems, type of cancer, tumor size, and treatment time.
Topics: Animals; Lycopene; Carotenoids; Anticarcinogenic Agents; Antineoplastic Agents; Antioxidants; Neoplasms
PubMed: 36841029
DOI: 10.1016/j.biopha.2023.114428 -
International Journal of Molecular... Jul 2022Recently, several chemotherapeutic drugs have been repositioned in neurological diseases, based on common biological backgrounds and the inverse comorbidity between... (Review)
Review
Recently, several chemotherapeutic drugs have been repositioned in neurological diseases, based on common biological backgrounds and the inverse comorbidity between cancer and neurodegenerative diseases. Fenretinide (all-trans-N-(4-hydroxyphenyl) retinamide, 4-HPR) is a synthetic derivative of all-trans-retinoic acid initially proposed in anticancer therapy for its antitumor effects combined with limited toxicity. Subsequently, fenretinide has been proposed for other diseases, for which it was not intentionally designed for, due to its ability to influence different biological pathways, providing a broad spectrum of pharmacological effects. Here, we review the most relevant preclinical and clinical findings from fenretinide and discuss its therapeutic role towards cancer and neurological diseases, highlighting the hormetic behavior of this pleiotropic molecule.
Topics: Antineoplastic Agents; Apoptosis; Fenretinide; Humans; Neoplasms; Tretinoin
PubMed: 35806431
DOI: 10.3390/ijms23137426 -
Nutrients Jun 2023Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol...
Dysregulation of lipid metabolism has been implicated in age-related macular degeneration (AMD), the leading cause of blindness among the elderly. Lecithin cholesterol acyltransferase (LCAT) is an important enzyme responsible for lipid metabolism, which could be regulated by DNA methylation during the development of various age-related diseases. This study aimed to assess the association between LCAT DNA methylation and the risk of AMD, and to examine whether plasma vitamin and carotenoid concentrations modified this association. A total of 126 cases of AMD and 174 controls were included in the present analysis. LCAT DNA methylation was detected by quantitative real-time methylation-1specific PCR (qMSP). Circulating vitamins and carotenoids were measured using reversed-phase high-performance liquid chromatography (RP-HPLC). DNA methylation of LCAT was significantly higher in patients with AMD than those in the control subjects. After multivariable adjustment, participants in the highest tertile of LCAT DNA methylation had a 5.37-fold higher risk (95% CI: 2.56, 11.28) of AMD compared with those in the lowest tertile. Each standard deviation (SD) increment of LCAT DNA methylation was associated with a 2.23-fold (95% CI: 1.58, 3.13) increased risk of AMD. There was a J-shaped association between LCAT DNA methylation and AMD risk (P = 0.03). Higher concentrations of plasma retinol and β-cryptoxanthin were significantly associated with decreased levels of LCAT DNA methylation, with the multivariate-adjusted β coefficient being -0.05 (95% CI: -0.08, -0.01) and -0.25 (95% CI: -0.42, -0.08), respectively. In joint analyses of LCAT DNA methylation and plasma vitamin and carotenoid concentrations, the inverse association between increased LCAT DNA methylation and AMD risk was more pronounced among participants who had a lower concentration of plasma retinol and β-cryptoxanthin. These findings highlight the importance of comprehensively assessing LCAT DNA methylation and increasing vitamin and carotenoid status for the prevention of AMD.
Topics: Humans; Aged; Vitamins; Carotenoids; Vitamin A; Phosphatidylcholine-Sterol O-Acyltransferase; DNA Methylation; Beta-Cryptoxanthin; Macular Degeneration; Vitamin K
PubMed: 37447314
DOI: 10.3390/nu15132985 -
Cells Jan 2022Retinoic acid (RA) functions as an essential signal for development of the vertebrate eye by controlling the transcriptional regulatory activity of RA receptors (RARs).... (Review)
Review
Retinoic acid (RA) functions as an essential signal for development of the vertebrate eye by controlling the transcriptional regulatory activity of RA receptors (RARs). During eye development, the optic vesicles and later the retina generate RA as a metabolite of vitamin A (retinol). Retinol is first converted to retinaldehyde by retinol dehydrogenase 10 (RDH10) and then to RA by all three retinaldehyde dehydrogenases (ALDH1A1, ALDH1A2, and ALDH1A3). In early mouse embryos, RA diffuses to tissues throughout the optic placode, optic vesicle, and adjacent mesenchyme to stimulate folding of the optic vesicle to form the optic cup. RA later generated by the retina is needed for further morphogenesis of the optic cup and surrounding perioptic mesenchyme; loss of RA at this stage leads to microphthalmia and cornea plus eyelid defects. RA functions by binding to nuclear RARs at RA response elements (RAREs) that either activate or repress transcription of key genes. Binding of RA to RARs regulates recruitment of transcriptional coregulators such as nuclear receptor coactivator (NCOA) or nuclear receptor corepressor (NCOR), which in turn control binding of the generic coactivator p300 or the generic corepressor PRC2. No genes have been identified as direct targets of RA signaling during eye development, so future studies need to focus on identifying such genes and their RAREs. Studies designed to learn how RA normally controls eye development in vivo will provide basic knowledge valuable for determining how developmental eye defects occur and for improving strategies to treat eye defects.
Topics: Animals; Mice; Organogenesis; Retina; Retinaldehyde; Tretinoin; Vitamin A
PubMed: 35159132
DOI: 10.3390/cells11030322 -
Nutrients Jun 2023This study aimed to assess associations between forms of vitamin A and E (both individually and collectively) and the risk of prostate cancer, as well as identify...
PURPOSE
This study aimed to assess associations between forms of vitamin A and E (both individually and collectively) and the risk of prostate cancer, as well as identify potential effect modifiers.
METHODS
Utilizing data from the Singapore Prostate Cancer Study, a hospital-based case-control study, we measured the serum concentrations of 15 different forms of vitamins A and E in 156 prostate cancer patients and 118 control subjects, using a high-performance liquid chromatography technique. These forms included retinol, lutein, zeaxanthin, α-cryptoxanthin, β-cryptoxanthin, α-carotene, β-carotene, lycopene, ubiquinone, δ-tocopherol, γ-tocopherol, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol. The odds ratio and 95% confidence interval for associations between vitamin A and E and prostate cancer risk were estimated using logistic regression models after adjustment for potential confounders. The analyses were further stratified by smoking and alcohol consumption status. The mixture effect of micronutrient groups was evaluated using weighted quantile sum regression.
RESULTS
Higher concentrations of retinol, lutein, α-carotene, β-carotene, ubiquinone, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol were significantly and positively associated with overall prostate cancer risk. Among ever-smokers, associations were stronger for lutein, β-cryptoxanthin and β-carotene compared with never-smokers. Among regular alcohol drinkers, associations were stronger for lutein, β-cryptoxanthin, ubiquinone, γ-tocotrienol and α-tocotrienol compared with non-regular alcohol drinkers. Retinol and α-tocotrienol contributed most to the group indices 'vitamin A and provitamin A carotenoids' and 'vitamin E', respectively.
CONCLUSIONS
Several serum vitamin A and E forms were associated with prostate cancer risk, with significant effect modification by smoking and alcohol consumption status. Our findings shed light on prostate cancer etiology.
Topics: Male; Humans; Vitamin A; beta Carotene; Tocotrienols; Lutein; alpha-Tocopherol; Beta-Cryptoxanthin; Ubiquinone; Case-Control Studies; Singapore; Prostatic Neoplasms
PubMed: 37375581
DOI: 10.3390/nu15122677 -
Nutrients Mar 2022Naturally occurring retinoids (retinol, retinal, retinoic acid, retinyl esters) are a subclass of β-apocarotenoids, defined by the length of the polyene side chain.... (Review)
Review
Naturally occurring retinoids (retinol, retinal, retinoic acid, retinyl esters) are a subclass of β-apocarotenoids, defined by the length of the polyene side chain. Provitamin A carotenoids are metabolically converted to retinal (β-apo-15-carotenal) by the enzyme β-carotene-15,15'-dioxygenase (BCO1) that catalyzes the oxidative cleavage of the central C=C double bond. A second enzyme β-carotene-9'-10'-dioxygenase cleaves the 9',10' bond to yield β-apo-10'-carotenal and β-ionone. Chemical oxidation of the other double bonds leads to the generation of other β-apocarotenals. Like retinal, some of these β-apocarotenals are metabolically oxidized to the corresponding β-apocarotenoic acids or reduced to the β-apocarotenols, which in turn are esterified to β-apocarotenyl esters. Other metabolic fates such as 5,6-epoxidation also occur as for retinoids. Whether the same enzymes are involved remains to be understood. β-Apocarotenoids occur naturally in plant-derived foods and, therefore, are present in the diet of animals and humans. However, the levels of apocarotenoids are relatively low, compared with those of the parent carotenoids. Moreover, human studies show that there is little intestinal absorption of intact β-apocarotenoids. It is possible that they are generated in vivo under conditions of oxidative stress. The β-apocarotenoids are structural analogs of the naturally occurring retinoids. As such, they may modulate retinoid metabolism and signaling. In deed, those closest in size to the C-20 retinoids-namely, β-apo-14'-carotenoids (C-22) and β-apo-13-carotenone (C-18) bind with high affinity to purified retinoid receptors and function as retinoic acid antagonists in transactivation assays and in retinoic acid induction of target genes. The possible pathophysiologic relevance in human health remains to be determined.
Topics: Animals; Carotenoids; Dioxygenases; Humans; Retinoids; Tretinoin; beta Carotene; beta-Carotene 15,15'-Monooxygenase
PubMed: 35406024
DOI: 10.3390/nu14071411