Tocopherol and phylloquinone biosynthesis in chloroplasts requires the phytol kinase VITAMIN E PATHWAY GENE5 (VTE5) and the farnesol kinase (FOLK).

Chlorophyll degradation causes the release of phytol, which is converted into phytyl diphosphate (phytyl-PP) by phytol kinase (VITAMIN E PATHWAY GENE5 [VTE5]) and phytyl phosphate (phytyl-P) kinase (VTE6). The kinase pathway is important for tocopherol synthesis, as the Arabidopsis (Arabidopsis thaliana) vte5 mutant contains reduced levels of tocopherol. Arabidopsis harbors one paralog of VTE5, farnesol kinase (FOLK) involved in farnesol phosphorylation. Here, we demonstrate that VTE5 and FOLK harbor kinase activities for phytol, geranylgeraniol, and farnesol with different specificities. While the tocopherol content of the folk mutant is unchanged, vte5-2 folk plants completely lack tocopherol. Tocopherol deficiency in vte5-2 plants can be complemented by overexpression of FOLK, indicating that FOLK is an authentic gene of tocopherol synthesis. The vte5-2 folk plants contain only ∼40% of wild-type amounts of phylloquinone, demonstrating that VTE5 and FOLK both contribute in part to phylloquinone synthesis. Tocotrienol and menaquinone-4 were produced in vte5-2 folk plants after supplementation with homogentisate or 1,4-dihydroxy-2-naphthoic acid, respectively, indicating that their synthesis is independent of the VTE5/FOLK pathway. These results show that phytyl moieties for tocopherol synthesis are completely but, for phylloquinone production, only partially derived from geranylgeranyl-chlorophyll and phytol phosphorylation by VTE5 and FOLK.

Variable carbon isotope fractionation of photosynthetic communities over depth in an open-ocean euphotic zone.

Marine particulate organic carbon (POC) contributes to carbon export, food webs, and sediments, but uncertainties remain in its origins. Globally, variations in stable carbon isotope ratios (δ13C values) of POC between the upper and lower euphotic zones (LEZ) indicate either varying aspects of photosynthetic communities or degradative alteration of POC. During summertime in the subtropical north Atlantic Ocean, we find that δ13C values of the photosynthetic product phytol decreased by 6.3‰ and photosynthetic carbon isotope fractionation (εp) increased by 5.6‰ between the surface and the LEZ-variation as large as that found in the geologic record during major carbon cycle perturbations, but here reflecting vertical variation in δ13C values of photosynthetic communities. We find that simultaneous variations in light intensity and phytoplankton community composition over depth may be important factors not fully accounted for in common models of photosynthetic carbon isotope fractionation. Using additional isotopic and cell count data, we estimate that photosynthetic and non-photosynthetic material (heterotrophs or detritus) contribute relatively constant proportions of POC throughout the euphotic zone but are isotopically more distinct in the LEZ. As a result, the large vertical differences in εp result in significant, but smaller, differences in the δ13C values of total POC across the same depths (2.7‰). Vertical structuring of photosynthetic communities and export potential from the LEZ may vary across current and past ocean ecosystems; thus, LEZ photosynthesis may influence the exported and/or sedimentary δ13C values of both phytol and total organic carbon and affect interpretations of εp over geologic time.

Abscisic acid triggers vitamin E accumulation by transient transcript activation of VTE5 and VTE6 in sweet cherry fruits.

Tocopherols are lipophilic antioxidants known as vitamin E and synthesized from the condensation of two metabolic pathways leading to the formation of homogentisate and phytyl diphosphate. While homogentisate is derived from tyrosine metabolism, phytyl diphosphate may be formed from geranylgeranyl diphosphate or phytol recycling from chlorophyll degradation. Here, we hypothesized that abscisic acid (ABA) could induce tocopherol biosynthesis in sweet cherries by modifying the expression of genes involved in vitamin E biosynthesis, including those from the phytol recycling pathway. Hence, the expression of key tocopherol biosynthesis genes was determined together with vitamin E and chlorophyll contents during the natural development of sweet cherries on the tree. Moreover, the effects of exogenously applied ABA on the expression of key tocopherol biosynthesis genes were also investigated during on-tree fruit development, and tocopherols and chlorophylls contents were analyzed. Results showed that the expression of tocopherol biosynthesis genes, including VTE5, VTE6, HPPD and HPT showed contrasting patterns of variation, but in all cases, increased by 2- and 3-fold over time during fruit de-greening. This was not the case for GGDR and VTE4, the first showing constitutive expression during fruit development and the second with marked down-regulation at ripening onset. Furthermore, exogenous ABA stimulated the production of both α- and γ-tocopherols by 60% and 30%, respectively, promoted chlorophyll degradation and significantly enhanced VTE5 and VTE6 expression, and also that of HPPD and VTE4, altogether increasing total tocopherol accumulation. In conclusion, ABA increases promote the transcription of phytol recycling enzymes, which may contribute to vitamin E biosynthesis during fruit development in stone fruits like sweet cherries.

Genome-wide association identifies a missing hydrolase for tocopherol synthesis in plants.

The tocopherol biosynthetic pathway, encoded by VTE genes 1 through 6, is highly conserved in plants but most large effect quantitative trait loci for seed total tocopherols (totalT) lack VTE genes, indicating other activities are involved. A genome-wide association study of Arabidopsis seed tocopherols showed five of seven significant intervals lacked VTE genes, including the most significant, which mapped to an uncharacterized, seed-specific, envelope-localized, alpha/beta hydrolase with esterase activity, designated AtVTE7. Atvte7 null mutants decreased seed totalT 55% while a leaky allele of the maize ortholog, ZmVTE7, decreased kernel and leaf totalT 38% and 49%, respectively. Overexpressing AtVTE7 or ZmVTE7 partially or fully complemented the Atvte7 seed phenotype and increased leaf totalT by 3.6- and 6.9-fold, respectively. VTE7 has the characteristics of an esterase postulated to provide phytol from chlorophyll degradation for tocopherol synthesis, but bulk chlorophyll levels were unaffected in vte7 mutants and overexpressing lines. Instead, levels of specific chlorophyll biosynthetic intermediates containing partially reduced side chains were impacted and strongly correlated with totalT. These intermediates are generated by a membrane-associated biosynthetic complex containing protochlorophyllide reductase, chlorophyll synthase, geranylgeranyl reductase (GGR) and light harvesting-like 3 protein, all of which are required for both chlorophyll and tocopherol biosynthesis. We propose a model where VTE7 releases prenyl alcohols from chlorophyll biosynthetic intermediates, which are then converted to the corresponding diphosphates for tocopherol biosynthesis.

Socialane, a Nonaprenyl Terpene Hydrocarbon Surface Lipid from the Collembola Hypogastrura socialis.

Springtails use unique compounds for their outermost epicuticular wax layer, often of terpenoid origin. We report here the structure and synthesis of socialane, the major cuticular constituent of the Collembola Hypogastrura socialis. Socialane is also the first regular nonaprenyl terpene with a cyclic head group. The saturated side chain has seven stereogenic centers, making the determination of the configuration difficult. We describe here the identification of socialane and a synthetic approach using the building blocks farnesol and phytol, enantioselective hydrogenation, and α-alkylation of sulfones for the synthesis of various stereoisomers. NMR experiments showed the presence of an anti-configuration of the methyl groups closest to the benzene ring and that the other methyl groups of the polyprenyl side-chain are not uniformly configured. Furthermore, socialane is structurally different from [6+2]-terpene viaticene of the closely related H. viatica, showing species specificity of the epicuticular lipids of this genus and hinting at a possible role of surface lipids in the communication of these gregarious arthropods.

New Phytol Derivatives with Increased Cosmeceutical Potential.

Natural compounds are widely incorporated into cosmetic products for many purposes. Diterpenes often function as fragrances, enhancing the sensory experience of these formulations. However, current trends in cosmetic science aim to develop multifunctional products, where compounds traditionally used for texture or fragrance also possess biological activities that contribute to the product's efficacy. In this context, this study focuses on synthesizing derivatives of phytol-a compound already presents in cosmetic formulations-to enhance its anti-aging properties. The derivatives were synthesized through esterification with substituted benzoic and cinnamic acids, known for their antioxidant and enzyme inhibition properties. Reaction yields ranged from 91.0% to 5.2%, depending on the substituents in acid derivatives. The structures of the synthesized compounds were confirmed through NMR and MS techniques. Both the natural and newly synthesized derivatives were evaluated for their cosmeceutical potential using antioxidant assays and inhibition assays for tyrosinase, elastase, collagenase, and hyaluronidase. This work presents the first report of the synthesis and cosmetic evaluation of several of these derivatives. Comparing with phytol (1), which presented an IC50 of 77.47 µM, four of the derivatives presented improved tyrosinase inhibitory activity, with phytyl 4-methoxybenzoate being the most active (IC50 = 27.9 µM), followed by phytyl benzoate with an IC50 of 34.73 µM. Substitutions at other positions on the aromatic ring were less effective. Molecular docking studies confirmed that the modifications potentiated a stronger interaction between the synthesized compounds and tyrosinase.

Zein/fucoidan-coated phytol nanoliposome: preparation, characterization, physicochemical stability, in vitro release, and antioxidant activity.

BACKGROUND: To improve phytol bioavailability, a novel method of magnetic stirring and high-pressure homogenization (HPH) combination was used to prepare zein/fucoidan-coated phytol nanoliposomes (P-NL-ZF). The characterization, the simulated in vitro digestion, and the antioxidant activity of these phytol nanoliposomes from the different processes have been studied. RESULTS: Based on the results of dynamic light scattering (DLS) and gas chromatography-mass spectrometer (GC-MS) analysis, P-NL-ZF prepared through the combination of magnetic stirring and HPH exhibited superior encapsulation efficiency at 76.19% and demonstrated exceptional physicochemical stability under a series of conditions, including storage, pH, and ionic in comparison to single method. It was further confirmed that P-NL-ZF by magnetic stirring and HPH displayed a uniform distribution and regular shape through transmission electron microscopy (TEM). Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) analysis showed that electrostatic interactions and hydrogen bonding were the primary driving forces for the formation of composite nanoliposomes. Additionally, an in vitro digestion study revealed that multilayer composite nanoliposomes displayed significant and favorable slow-release properties (58.21%) under gastrointestinal conditions compared with traditional nanoliposomes (82.36%) and free phytol (89.73%). The assessments of chemical and cell-based antioxidant activities demonstrated that the coating of zein/fucoidan on phytol nanoliposomes resulted in enhanced effectiveness in scavenging activity of ABTS free radical and hydroxyl radical and mitigating oxidative damage to HepG2 cells. CONCLUSION: Based on our studies, the promising delivery carrier of zein/fucoidan-coated nanoliposomes is contributed to the encapsulation of hydrophobic natural products and enhancement of their biological activity. © 2024 Society of Chemical Industry.

2-Hydroxy-phytanoyl-CoA lyase (AtHPCL) is involved in phytol metabolism in Arabidopsis.

During chlorophyll degradation, large amounts of the isoprenoid alcohol phytol are released. The pathway of phytol catabolism has been studied in humans, because chlorophyll is part of the human diet, but little is known for plants. In humans, phytanoyl-CoA derived from phytol is degraded via α-oxidation by phytanoyl-CoA hydroxylase (PAHX) and 2-hydroxy-phytanoyl-CoA lyase (HPCL). Arabidopsis contains two sequences homologous to the human proteins AtPAHX and AtHPCL. Insertional mutants of Arabidopsis (pahx, hpcl) were grown under N deprivation to stimulate chlorophyll breakdown or supplemented with phytol to increase the endogenous amount of phytol. During N deprivation, chlorophyll, phytol, phytenal, upstream metabolites of phytol breakdown, and tocopherol and fatty acid phytyl esters, alternative phytol-derived lipids, accumulated in pahx and hpcl mutants, in line with the scenario that the mutations interfere with phytol degradation. AtHPCL was localized to the peroxisomes. Expression analysis of the AtHPCL sequence in the yeast Δpxp1 or Δmpo1 mutants followed by supplementation with 2-hydroxy-palmitic acid and enzyme assays of peroxisomal proteins from Col-0 and hpcl plants with 2-hydroxy-stearoyl-CoA revealed that AtHPCL harbors 2-hydroxy-acyl-CoA lyase activity. The α-dioxygenases αDOX1 and αDOX2 are involved in α-oxidation of fatty acids and could be involved in an alternative pathway of phytol degradation. However, phytol-related lipids in the αdox1, αdox2, or αdox1 αdox2 mutants were not altered compared with Col-0, indicating that αDOX1 and αDOX2 are not involved in phytol degradation. These results demonstrate that phytol degradation in Arabidopsis involves α-oxidation by AtPAHX and AtHPCL, but that it is independent of αDOX1/αDOX2.

Phytol recycling: essential, yet not limiting for tomato fruit tocopherol accumulation under normal growing conditions.

Tocopherols are potent membrane-bound antioxidant molecules that are paramount for plant physiology and also important for human health. In the past years, chlorophyll catabolism was identified as the primary source of phytyl diphosphate for tocopherol synthesis by the action of two enzymes, PHYTOL KINASE (VTE5) and PHYTHYL PHOSPHATE KINASE (VTE6) that are able to recycle the chlorophyll-derived phytol. While VTE5 and VTE6 were proven essential for tocopherol metabolism in tomato fruits, it remains unknown whether they are rate-limiting steps in this pathway. To address this question, transgenic tomato plants expressing AtVTE5 and AtVTE6 in a fruit-specific manner were generated. Although ripe transgenic fruits exhibited higher amounts of tocopherol, phytol recycling revealed a more intimate association with chlorophyll than with tocopherol content. Interestingly, protein-protein interactions assays showed that VTE5 and VTE6 are complexed, channeling free phytol and phytyl-P, thus mitigating their cytotoxic nature. Moreover, the analysis of tocopherol accumulation dynamics in roots, a chlorophyll-devoid organ, revealed VTE5-dependent tocopherol accumulation, hinting at the occurrence of shoot-to-root phytol trafficking. Collectively, these results demonstrate that phytol recycling is essential for tocopherol biosynthesis, even in chlorophyll-devoid organs, yet it is not the rate-limiting step for this pathway under normal growth conditions.

Triacylglycerol and phytyl ester synthesis in Synechocystis sp. PCC6803.

Cyanobacteria are unicellular prokaryotic algae that perform oxygenic photosynthesis, similar to plants. The cells harbor thylakoid membranes composed of lipids related to those of chloroplasts in plants to accommodate the complexes of photosynthesis. The occurrence of storage lipids, including triacylglycerol or wax esters, which are found in plants, animals, and some bacteria, nevertheless remained unclear in cyanobacteria. We show here that the cyanobacterium Synechocystis sp. PCC6803 accumulates both triacylglycerol and wax esters (fatty acid phytyl esters). Phytyl esters accumulate in higher levels under abiotic stress conditions. The analysis of an insertional mutant revealed that the acyltransferase slr2103, with sequence similarity to plant esterase/lipase/thioesterase (ELT) proteins, is essential for triacylglycerol and phytyl ester synthesis in Synechocystis The recombinant slr2103 enzyme showed acyltransferase activity with phytol and diacylglycerol, thus producing phytyl esters and triacylglycerol. Acyl-CoA thioesters were the preferred acyl donors, while acyl-ACP (acyl carrier protein), free fatty acids, or galactolipid-bound fatty acids were poor substrates. The slr2103 protein sequence is unrelated to acyltransferases from bacteria (AtfA) or plants (DGAT1, DGAT2, PDAT), and therefore establishes an independent group of bacterial acyltransferases involved in triacylglycerol and wax ester synthesis. The identification of the gene slr2103 responsible for triacylglycerol synthesis in cyanobacteria opens the possibility of using prokaryotic photosynthetic cells in biotechnological applications.

Exploring Echinops polyceras Boiss. from Jordan: Essential Oil Composition, COX, Protein Denaturation Inhibitory Power and Antimicrobial Activity of the Alcoholic Extract.

In this article, we present the first detailed analysis of the hydro-distilled essential oil (HDEO) of the inflorescence heads of Echinops polyceras Boiss. (Asteraceae) from the flora of Jordan, offering observations at different growth (pre-flowering, full-flowering and post-flowering) stages. Additionally, we investigated the methanolic extract obtained from the aerial parts of the plant material at the full flowering stage in order to determine its inhibitory activity in terms of COX and protein denaturation and evaluate its antimicrobial effects against S. aureus (Gram-positive) and E. coli (Gram-negative) bacteria. Performing GC/MS analysis of HDEO, obtained from the fresh inflorescence heads at the different growth stages, resulted in the identification of 192 constituents. The main class of compounds detected in these three stages comprised aliphatic hydrocarbons and their derivatives, which amounted to 50.04% (pre-flower), 40.28% (full-flower) and 41.34% (post-flower) of the total composition. The oils also contained appreciable amounts of oxygenated terpenoids, primarily sesquiterpenoids and diterpenoids. The pre-flowering stage was dominated by (2E)-hexenal (8.03%) in addition to the oxygenated diterpene (6E,10E)-pseudo phytol (7.54%). The full-flowering stage primarily contained (6E,10E)-pseudo phytol (7.84%), ß-bisabolene (7.53%, SH) and the diterpene hydrocarbon dolabradiene (5.50%). The major constituents detected in the HDEO obtained at the post-flowering stage included the oxygenated sesquiterpenoid intermedeol (5.53%), the sesquiterpene hydrocarbon (E)-caryophyllene (5.01%) and (6E,10E)-pseudo phytol (4.47%). The methanolic extract obtained from air-dried aerial parts of E. polyceras displayed more COX-2 inhibition than COX-1 inhibition at a concentration level of 200 µg/mL. The extract exhibited a capacity to inhibit protein denaturation that was comparable with respect to the activity of diclofenac sodium and displayed moderate levels of antimicrobial activity against both bacterial species. The current results demonstrate the need to perform further detailed phytochemical investigations to isolate and characterize active constituents.

The tail of chlorophyll: Fates for phytol.

Understanding the pathways involved in chlorophyll breakdown provides a molecular map to the color changes observed in plant life on a global scale each fall. Surprisingly, little is known about the fate of phytol, chlorophyll's 20-carbon branched-chain tail, during this process. A recent study from Gutbrod et al. provides evidence using physiological, genetic, and exquisitely sensitive analytical approaches that phytenal is an intermediate in plant phytol catabolism. These insights and techniques open the door to further investigation of this complicated metabolic system, with implications for plant health and agriculture.

Phytol derived from chlorophyll hydrolysis in plants is metabolized via phytenal.

Phytol is the isoprenoid alcohol bound in ester linkage to chlorophyll, the most abundant photosynthetic pigment in plants. During leaf senescence, large amounts of phytol are released by chlorophyll degradation. However, the pathway of phytol catabolism in plants is unknown. We hypothesized that phytol degradation in plants might involve its oxidation into the long-chain aldehyde phytenal. Using GC-MS for aldehyde quantification after derivatization with methylhydroxylamine, phytenal was identified in leaves, whereas other long-chain aldehydes (phytanal and pristanal) were barely detectable. We found that phytenal accumulates during chlorotic stresses, for example, salt stress, dark-induced senescence, and nitrogen deprivation. The increase in the phytenal content is mediated at least in part independently of enzyme activities, and it is independent of light. Characterization of phytenal accumulation in the pao1 mutant affected in chlorophyll degradation revealed that phytenal is an authentic phytol metabolite derived from chlorophyll breakdown. The increase in phytenal was even stronger in mutants affected in the production of other phytol metabolites including vte5-2 (tocopherol deficient) and pes1 pes2 (fatty acid phytyl ester deficient). Therefore, phytenal accumulation is controlled by competing, alternative pathways of phosphorylation (leading to tocopherol production) or esterification (fatty acid phytyl ester production). As a consequence, the content of phytenal is maintained at low levels, presumably to minimize its toxic effects caused by its highly reactive aldehyde group that can form covalent bonds with and inactivate the amino groups of proteins.

Phytol loaded PLGA nanoparticles ameliorate scopolamine-induced cognitive dysfunction by attenuating cholinesterase activity, oxidative stress and apoptosis in Wistar rat.

OBJECTIVE: Alzheimer's disease (AD) is an acquired neurological disorder of cognitive and behavioral impairments, with a long and progressive route. Currently, efforts are being made to develop potent drugs that target multiple pathological mechanisms that drive the successful treatment of AD in human beings. The development of nano-drug delivery systems has recently emerged as an effective strategy to treat AD. METHODS: In the present study, the protective effect of Phytol and Phytol loaded Poly Lactic-co-Glycolic Acid nanoparticles (Phytol-PLGANPs) were evaluated in Wistar rat scopolamine model of AD. RESULTS AND DISCUSSION: The consumption of Phytol and Phytol-PLGANPs significantly ameliorated the cognitive deficits caused by scopolamine on spatial and short term memory. Phytol and Phytol-PLGANPs significantly enhanced the cholinergic effect by inhibiting both acetylcholinesterase and butyrylcholinesterase (AChE & BuChE), ß-secretase 1 (BACE1) activity, attenuating macromolecular damage, reducing reactive oxygen species (ROS) and reactive nitrogen species (RNS) level by activating antioxidative defense system (Superoxide dismutase and catalase) and restoring glutathione metabolizing enzyme systems (Glutathione S-transferase) and also regulating the apoptotic mediated cell death. Moreover, in vivo toxicity study suggests that Phytol and Phytol-PLGANPs did not cause any adverse pathological alteration in rats treated with a higher concentration of Phytol-PLGANPs (200 mg/kg). Pharmacokinetic study revealed that Phytol-PLGANPs enhanced the biodistribution and sustained the release profile of phytol in the brain and plasma. CONCLUSION: Overall, the outcome of the study suggests that Phytol and Phytol-PLGANPs act as a potent candidate with better anti-amnesic effects and multi-faceted neuroprotective potential against scopolamine-induced memory dysfunction in Wistar rats.

Cytotoxic Potential of the Marine Diatom Thalassiosira rotula: Insights into Bioactivity of 24-Methylene Cholesterol.

Marine microalgae are receiving great interest as sustainable sources of bioactive metabolites for health, nutrition and personal care. In the present study, a bioassay-guided screening allowed identifying an enriched fraction from SPE separation of the methanolic extract of the marine diatom Thalassiosira rotula with a chemically heterogeneous composition of cytotoxic molecules, including PUFAs, the terpene phytol, the carotenoid fucoxanthin and the phytosterol 24-methylene cholesterol (24-MChol). In particular, this latter was the object of deep investigation aimed to gain insight into the mechanisms of action activated in two tumour cell models recognised as resistant to chemical treatments, the breast MCF7 and the lung A549 cell lines. The results of our studies revealed that 24-MChol, in line with the most studied ß-sitosterol (ß-SIT), showed cytotoxic activity in a 3-30 µM range of concentration involving the induction of apoptosis and cell cycle arrest, although differences emerged between the two sterols and the two cancer systems when specific targets were investigated (caspase-3, caspase-9, FAS and TRAIL).

Tissue Proteome of 2-Hydroxyacyl-CoA Lyase Deficient Mice Reveals Peroxisome Proliferation and Activation of ω-Oxidation.

Peroxisomal fatty acid α-oxidation is an essential pathway for the degradation of ß-carbon methylated fatty acids such as phytanic acid. One enzyme in this pathway is 2-hydroxyacyl CoA lyase (HACL1), which is responsible for the cleavage of 2-hydroxyphytanoyl-CoA into pristanal and formyl-CoA. Hacl1 deficient mice do not present with a severe phenotype, unlike mice deficient in other α-oxidation enzymes such as phytanoyl-CoA hydroxylase deficiency (Refsum disease) in which neuropathy and ataxia are present. Tissues from wild-type and Hacl1-/- mice fed a high phytol diet were obtained for proteomic and lipidomic analysis. There was no phenotype observed in these mice. Liver, brain, and kidney tissues underwent trypsin digestion for untargeted proteomic liquid chromatography-mass spectrometry analysis, while liver tissues also underwent fatty acid hydrolysis, extraction, and derivatisation for fatty acid gas chromatography-mass spectrometry analysis. The liver fatty acid profile demonstrated an accumulation of phytanic and 2-hydroxyphytanic acid in the Hacl1-/- liver and significant decrease in heptadecanoic acid. The liver proteome showed a significant decrease in the abundance of Hacl1 and a significant increase in the abundance of proteins involved in PPAR signalling, peroxisome proliferation, and omega oxidation, particularly Cyp4a10 and Cyp4a14. In addition, the pathway associated with arachidonic acid metabolism was affected; Cyp2c55 was upregulated and Cyp4f14 and Cyp2b9 were downregulated. The kidney proteome revealed fewer significantly upregulated peroxisomal proteins and the brain proteome was not significantly different in Hacl1-/- mice. This study demonstrates the powerful insight brought by proteomic and metabolomic profiling of Hacl1-/- mice in better understanding disease mechanism in fatty acid α-oxidation disorders.

Development of Galloyl Antioxidant for Dispersed and Bulk Oils through Incorporation of Branched Phytol Chain.

In this study, a novel galloyl phytol antioxidant was developed by incorporating the branched phytol chain with gallic acid through mild Steglich esterification. The evaluation of the radical scavenging activity, lipid oxidation in a liposomal model, and glycerol trioleate revealed its superior antioxidant activities in both dispersed and bulk oils. Then, the antioxidant capacity enhancement of galloyl phytol was further explored using thermal gravimetry/differential thermal analysis (TG/DTA), transmission electron microscopy (TEM), and molecular modeling. The EC50 values of GP, GPa, and GE were 0.256, 0.262, and 0.263 mM, respectively, which exhibited comparable DPPH scavenging activities. These investigations unveiled that the branched aliphatic chain enforced the coiled molecular conformation and the unsaturated double bond in the phytol portion further fixed the coiled conformation, which contributed to a diminished aggregation tendency and enhanced antioxidant activities in dispersed and bulk oils. The remarkable antioxidant performance of galloyl phytol suggested intriguing and non-toxic natural antioxidant applications in the food industry, such as effectively inhibiting the oxidation of oil and improvement of the quality and shelf life of the oil, which would contribute to the use of tea resources and extending the tea industry chain.

Clinical Potential of Himalayan Herb Bergenia ligulata: An Evidence-Based Study.

Herbal products have been used in traditional systems of medicine and by ethnic healers for ages to treat various diseases. Currently, it is estimated that about 80% of people worldwide use herbal traditional medicines against various ailments, partly due to easy accessibility and low cost, and the lower side effects they pose. Bergenia ligulata, a herb ranging from the Himalayas to the foothills, including the north-eastern states of India, has traditionally been used as a remedy against various diseases, most prominently kidney stones. The medicinal properties of B. ligulata have been attributed to bergenin, its most potent bioactive component. Apart from bergenin, the other compounds available in B. ligulata are arbutin, gallic acid, protocatechuic acid, chlorogenic acid, syringic acid, catechin, ferulic acid, afzelechin, paashaanolactone, caryophyllene, 1,8-cineole, ß-eudesmol, stigmasterol, ß-sitosterol, parasorbic acid, 3-methyl-2-buten-1-ol, phytol, terpinen-4-ol, tannic acid, isovalaric acid, avicularin, quercetin, reynoutrin, and sitoinoside I. This review summarizes various medicinal properties of the herb, along with providing deep insight into its bioactive molecules and their potential roles in the amelioration of human ailments. Additionally, the possible mechanism(s) of action of the herb's anti-urolithiatic, antioxidative, antipyretic, anti-diabetic, anti-inflammatory and hepatoprotective properties are discussed. This comprehensive documentation will help researchers to better understand the medicinal uses of the herb. Further studies on B. ligulata can lead to the discovery of new drug(s) and therapeutics for various ailments.

Chemical Composition and In Vitro Antioxidant Activity of Sida rhombifolia L. Volatile Organic Compounds.

In the current study, the phytochemical constituents of volatile organic compounds (VOCs) obtained from Sida rhombifolia L. were identified by GC-FID and GC-MS analysis. A total of 73 volatile organic compounds were identified. The major components of S. rhombifolia VOCs were identified as palmitic acid (21.56%), phytol (7.02%), 6,10,14-trimethyl-2-pentadecanone (6.30%), oleic acid (5.48%), 2-pentyl-furan (5.23%), and linoleic acid (3.21%). The VOCs are rich in fatty acids (32.50%), olefine aldehyde (9.59%), ketone (9.41%), enol (9.02%), aldehyde (8.63%), and ketene (6.41%). The antioxidant capacity of S. rhombifolia VOCs was determined by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid) diammonium salt (ABTS), and ferric reducing/antioxidant power (FRAP) methods with butylated hydroxytoluene (BHT) and Trolox as standard. The VOCs showed dose-dependent antioxidant activity with IC50 (50% inhibitory concentration) values of 5.48 ± 0.024 and 1.47 ± 0.012 mg/mL for DPPH and ABTS assays, respectively. FRAP antioxidant capacity was 83.10 ± 1.66 mM/g. The results show that the VOCs distilled from S. rhombifolia have a moderate antioxidant property that can be utilized as a natural botanical supplement or an antioxidant.

Understanding the Antilymphoma Activity of Annona macroprophyllata Donn and Its Acyclic Terpenoids: In Vivo, In Vitro, and In Silico Studies.

Annona macroprophyllata Donn (A. macroprophyllata) is used in traditional Mexican medicine for the treatment of cancer, diabetes, inflammation, and pain. In this work, we evaluated the antitumor activity of three acyclic terpenoids obtained from A. macroprophyllata to assess their potential as antilymphoma agents. We identified the terpenoids farnesyl acetate (FA), phytol (PT) and geranylgeraniol (Gg) using gas chromatography-mass spectroscopy (GC-MS) and spectroscopic (1H, and 13C NMR) methods applied to petroleum ether extract of leaves from A. macroprophyllata (PEAm). We investigated antitumor potential in Balb/c mice inoculated with U-937 cells by assessing brine shrimp lethality (BSL), and cytotoxic activity in these cells. In addition, to assess the potential toxicity of PEAm, FA, PT and Gg in humans, we tested their acute oral toxicity in mice. Our results showed that the three terpenoids exhibited considerable antilymphoma and cytotoxic activity. In terms of lethality, we determined a median lethal dose (LD50) for thirteen isolated products of PEAm. Gg, PT and AF all exhibited a higher lethality with values of 1.41 ± 0.42, 3.03 ± 0.33 and 5.82 ± 0.58 µg mL-1, respectively. To assess cytotoxic activity against U-937 cells, we calculated the mean cytotoxic concentration (CC50) and found that FA and PT were closer in respect to the control drug methotrexate (MTX, 0.243 ± 0.007 µM). In terms of antilymphoma activity, we found that FA, PT and Gg considerably inhibited lymph node growth, with median effective doses (ED50) of 5.89 ± 0.39, 6.71 ± 0.31 and 7.22 ± 0.51 mg kg-1 in females and 5.09 ± 0.66, 5.83 ± 0.50 and 6.98 ± 0.57mg kg -1 in males, respectively. Regarding acute oral toxicity, we classified all three terpenoids as category IV, indicating a high safety margin for human administration. Finally, in a molecular docking study of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, we found binding of terpenoids to some amino acids of the catalytic site, suggesting an effect upon activity with a resulting decrease in the synthesis of intermediates involved in the prenylation of proteins involved in cancer progression. Our findings suggest that the acyclic terpenoids FA, PT, and Gg may serve as scaffolds for the development of new treatments for non-Hodgkin's lymphoma.