Search

Phytosterols are structurally similar to cholesterol but they are much less absorbed (<2%) than cholesterol (>50%) in the intestine. We hypothesize that phytosterols are poor substrates of intestinal acyl-CoA: cholesterol acyltransferase 2 (ACAT2), and thus minimal phytosterol esters are formed and packed into chylomicrons, leading to their low absorption. Two isotope tracing models, including a radioactive hamster microsomal ACAT2 reaction model and a differentiated Caco-2 cell model, were established to examine the specificity of ACAT2 to various sterols, including cholesterol, sitosterol, stigmasterol, and campesterol. Both models consistently demonstrated that only cholesterol but not phytosterols could be efficiently esterified by ACAT2 in a time- and dose-dependent manner. Molecular docking further suggested that unfavorable interactions existed between ACAT2 and phytosterols. In conclusion, phytosterols are poor substrates of ACAT2 and thus minimally absorbed. This work provides a theoretical basis for the use of phytosterol-based supplements in treating dyslipidemia and preventing heart diseases., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Precisely controlling enzyme conformation to enhance catalytic performance is a highly sought-after yet challenging goal in the immobilization of biocatalysts. Excessively strong enzyme-carrier interactions can restrict enzyme dynamics and reduce catalytic efficiency, while excessively weak interactions may lead to enzyme leakage, thereby reducing reusability. In this study, we developed a novel strategy to finely regulate the interaction between the carrier and the enzyme through the adjustment of the ratio of amino and octadecyl functional groups. The expressed activity of the novel immobilized lipase, CRL@AOMR, was 1.32- and 2.34-fold higher than that of the monofunctional macroporous resin. Moreover, the synthesis of various phytosterol esters in solvent-free systems was conducted as a model reaction to investigate the utilization of CRL@AOMR in different reactions. Under optimized conditions, an impressive yield of 96.1% for phytosterol oleate was achieved and a yield of 76.2% was maintained even after six cycles of utilization (288 h). This study demonstrates the potential feasibility of developing immobilization strategies via dual modification of amino and alkyl groups, which is a potential general strategy for other enzymes with surface lysine.

Leea indica (Burm. f.) Merr. (Vitaceae) is used for the treatment of wounds in traditional medicine practiced in Sri Lanka. The current study is carried out to investigate its wound healing potential in terms of in vitro cell migration and proangiogenic activity. The scratch wound assay (SWA) guided fractionation of dichloromethane extract of L. indica led to the isolation of a rare phytosterol, stigmast-5-en-3 β ,7 α ,22 α -triol ( 1 ), betulin ( 2 ), lupeol ( 3 ), and β -sitosterol ( 4 ) all of which showed enhanced cell migration in SWA and significant proangiogenic response in chorioallantoic membrane (CAM) assay. The identities of compounds 1 - 4 were established by the analysis of NMR spectroscopic data and comparison with those reported. This is the first report of the occurrence of compounds 1 and 2 in L. indica .

Oleogels are innovative structured fat systems that can replace detrimental lipids and saturated fats. Among the various gelators used to construct oleogels, phytosterols are regarded as potential oleogelators due to ability to lower blood cholesterol levels and protect patients from cardiovascular illnesses, although little research has been conducted on phytosterols. This article examines the formation, characterization, and application of phytosterol-based oleogels in detail. The oleogelation behaviors of phytosterol-based oleogels are affected by their formulation, which includes phytosterol type, combined oleogelator, proportion, concentration and oil type. These oleogels exhibit potential applications as solid fat substitutes without affecting the texture or sensory properties of food products or as effective delivery vehicles. To encourage the research and implementation of phytosterol-based oleogels, we will ultimately not only highlight problems related to their use in food processing, but also provide a few viewpoints, with the goal of providing fresh insights for advancing trends., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

In order to prevent the photooxidation of phytosterols, a new type of Pickering emulsion was developed by regulating the oriented distribution of antioxidants in colloidal lipid particles (CLPs) at the oil-water interface. High-melting-point and low-melting-point lipids were tested to modulate their protective effect against phytosterols photooxidation. Results showed that CLPs could stabilize Pickering emulsion and encapsulate antioxidants, providing a dual functional delivery system for phytosterols protection. The Pickering emulsion formed had a particle size of around 350-820 nm, and the crystallization and melting temperatures of tripalmitin particles were approximately 32 °C and 63.8 °C, respectively. The addition of tributyrin or tricaprylin reduced the crystallization and melting temperatures of Pal CLPs and improved the photooxidation emulsion stability. The prepared Pickering emulsion remained stable for a maximum of 12 days under accelerated light-induced oxidation. Among all formulations, the emulsion primarily composed of tripalmitin CLPs, with added tributyrin and resveratrol, exhibited the highest photooxidation stability., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Phytosterol, recognized for its health benefits, is predominantly extracted from plants and exhibits significantly reduced stability under varying light conditions. Their photooxidation is significantly influenced by emulsion interfaces. This study examined the mechanism of interface structure on phytosterol photooxidation with unparalleled molecular precision, utilizing molecular dynamics simulations and experimental procedures. Hydrogen bonding between the hydroxyl group at the C3 position of phytosterols and water molecules, coupled with van der Waals forces between the hydrophobic regions and the oil phase, induced phytosterol molecules to disperse toward the interface. The elevated polarity of the oil phase, specifically in tributyrin, facilitated the permeation of water molecules into the oil phase. This was achieved by diminishing the emulsion's interfacial tension, thereby fostering the development of more interface or micelles, and accelerating the photooxidation process of phytosterols. These simulations unraveled that the preponderance of phytosterol distribution is localized and oxidized at the oil-water interface., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Epithelial Ovarian Cancer (EOC) presents a global health concern, necessitating the development of innovative therapeutic strategies to combat its impact. This study was employed to investigate the unexplored therapeutic efficacy of Cynodon dactylon phytochemicals against EOC using a multifaceted computational approach. A total of 19 out of 89 rigorously curated phytochemicals were assessed as potential drug targets via ADMET profiling, while protein-protein interaction analysis scrutinized the top 20 hub genes among 264 disease targets, revealing their involvement in cancer-related pathways and underscoring their significance in EOC pathogenesis. In molecular docking, Stigmasterol acetate showed the highest binding affinity (-10.9 kcal/mol) with Poly [ADP-ribose] polymerase-1 (PDB: 1UK1), while Arundoin and Beta-Sitosterol exhibited strong affinities (-10.4 kcal/mol and -10.1 kcal/mol, respectively); additionally, Beta-Sitosterol interacting with Mitogen-activated protein kinase 3 (PDB: 4QTB) showed a binding affinity of -10.1 kcal/mol, forming 2 hydrogen bonds and a total of 10 bonds with 10 residues. Molecular dynamics simulations exhibited the significant structural stability of the Beta-Sitosterol-4QTB complex with superior binding free energy (-36.61 kcal/mol) among the three complexes. This study identified C. dactylon phytosterols, particularly Beta-Sitosterol, as effective in targeting MAPK3 and PARP1 to combat EOC, laying the groundwork for further experimental validation and drug development efforts., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (β-SIT) and stigmasterol (STIG). The objective of the study was to evaluate the anti-inflammatory and toxicity activities of the hexane partition of P. aculeata (PHEX), as well as β-SIT and STIG. PHEX was prepared and the phytosterols were quantified. In terms of toxicity against L929 fibroblast cells, PHEX showed toxicity up to 200 μg/mL; STIG and β-SIT showed toxicity up to 25 μg/mL. PHEX inhibited 66 % of nitric oxide radicals, while STIG and β-SIT inhibited 33.73 % and 34.94 %, respectively. In an anti-inflammatory test against Zophobas morio larvae, all samples significantly reduced hemocyte levels. Additionally, the LD50 values were calculated: 229.6 mg/kg for PHEX, 101.5 mg/kg for STIG, and 103.8 mg/kg for β-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Candida auris, a pathogenic fungus, has posed significant challenges to conventional medical treatments due to its increasing resistance to antifungal agents. Consequently, due to their promising pharmacological properties, there is a compelling interest in exploring novel bioactive compounds, such as phytosterols and triterpenes. This study aimed to conduct virtual screening utilizing computational methods, including ADMET, molecular docking, and molecular dynamics, to assess the activity and feasibility of phytosterols extracted from Cryptostegia grandiflora as potential therapeutic agents. Computational predictions suggest that compounds bearing structural similarities to Fsp 3 -rich molecules hold promise for inhibiting enzymes and G protein-coupled receptor (GPCR) modulators, with particular emphasis on ursolic acid, which, in its conjugated form, exhibits high oral bioavailability and metabolic stability, rendering it a compelling drug candidate. Molecular docking calculations identified ursolic acid and stigmasterol as promising ligands. While stigmasterol displayed superior affinity during molecular dynamics simulations, it exhibited instability, contrasting with ursolic acid's slightly lower affinity yet sustained stability throughout the dynamic assessments. This suggests that ursolic acid is a robust candidate for inhibiting the FKBP12 isomerase in C. auris. Moreover, further investigations could focus on experimentally validating the molecular docking predictions and evaluating the efficacy of ursolic acid as an FKBP12 isomerase inhibitor in models of C. auris infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hydrophobic bioactive compounds like astaxanthin (AST) exhibit poor water solubility and low bioavailability. Liposomes, which serve as nanocarriers, are known for their excellent biocompatibility and minimal immunogenicity. Traditionally, liposomes have been primarily constructed using phospholipids and cholesterol. However, the intake of cholesterol may pose a risk to human health. Phytosterol ester was reported to reduce level of cholesterol and improve properties of liposomes. In this study, phytosterol oleate was used to prepare liposomes instead of cholesterol to deliver AST (AST-P-Lip). The size range of AST-P-Lip was 100-220 nm, and the morphology was complete and uniform. In vitro studies showed that AST-P-Lip significantly enhanced the antioxidant activity and oral bioavailability of AST. During simulated digestion, AST-P-Lip protected AST from damage by gastric and intestinal digestive fluid. Additionally, AST-P-Lip had a good storage stability and safety. These results provide references for the preparation of novel liposomes and the delivery of bioactive compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Traditional berries are small fruits and are widely distributed in the Canadian prairies. The current study investigates the lipophilic bioactive compounds such as fatty acids, phytosterols, and terpenes, and their bioactivities, such as lipid peroxidation, as well as the antihypertensive activities of fourteen underutilized Canadian wild berries. These berries include Saskatoon berries ( Amelanchier alnifolia ), gooseberries ( Ribes hirtellum ), wild grapes ( Vitis riparia ), blackcurrants ( Ribes nigrum ), redcurrants ( Ribes rubrum ), haskap berries ( Lonicera caerulea ), wild raspberries ( Rubus idaeus ), wild blueberries ( Vaccinium angustifolium ), chokeberries ( Aronia melanocarpa ), buckthorn ( Rhamnus cathartica ), highbush cranberries ( Viburnum trilobum ), chokecherries ( Prunus virginiana ), nannyberries ( Viburnum lentago ) and snowberries ( Symphoricarpos albus ). The fatty acids, phytosterols, and terpenes were identified using Gas Chromatography-Mass Spectrometry (GC-MS). Lipid peroxidation and the antihypertensive activity assessed by measuring the berries' angiotensin converting enzyme 1 (ACE1) inhibitory activity were determined using in vitro methods. Notably, wild grapes exhibited the highest ( p < 0.05) total fat content (7659 ± 312 μg per g DW), followed by haskap berries (4650 ± 184 μg per g DW). Polyunsaturated fatty acids (PUFAs) were highest ( p < 0.05) in wild grapes (74%). Predominant phytosterols and terpenes identified in Canadian wild berries included β-sitosterol, isofucosterol, phytol, and α-amyrin. Saskatoon berries and gooseberries showed a distinct phytosterol and terpene profile compared to the other wild berries. Snowberries demonstrated the highest ( p < 0.05) lipid peroxidation and the lowest ( p < 0.05) angiotensin converting enzyme (ACE1) activity. This research provides valuable insights into the lipophilic bioactive compounds and their potential activities in vitro of the Canadian wild berries, offering a foundation for further exploration and potential applications in the context of nutraceuticals and functional foods.

Breast cancer remains a global health challenge, and innovative strategies are required to target estrogen receptor α (ERα), a key player in its development. This study investigates the potential of campesterol, a natural phytosterol, as an ERα inhibitor for breast cancer. Our approach integrates in silico , in vitro , and ex vivo experiments to assess the therapeutic potential of campesterol. In silico analyses highlight campesterol as a promising ERα ligand with favorable binding affinities and dynamic properties. Structural analysis reveals conformational changes in ERα upon campesterol binding. In vitro studies confirm the selective growth inhibition of campesterol against ERα-positive breast cancer cells. This study extends to ER+ breast cancer patient-derived organoids (PDOs), showing the effectiveness of campesterol in ERα-positive breast cancer PDOs. Importantly, it emphasizes the receptor-specific nature of campesterol, providing insights into its context-dependent action. In conclusion, campesterol displays potential as an ERα inhibitor, offering new avenues for ER+ breast cancer treatment.

Phytosterol (PS) is a steroid, and its bioavailability can be enhanced by interacting with protein in the C-24 hydroxyl group. The interaction between sterols and amino acid residues in proteins can be enhanced by enzymatic hydrolysis. Phytosterol and whey insulation hydrolysates (WPH1-4) fabricated by the Alcalase enzyme at different enzymatic hydrolysis times were selected as delivery systems to simulate sterol C-24 hydroxyl group interaction with protein. Increasing hydrolysis time can promote the production of β-Lg, which raises the ratio of β-turn in the secondary structure and promotes the formation of interaction between WPH and PS. The correlation coefficient between hydrogen bonds and encapsulation efficiency (EE) and bioaccessibility is 0.91 and 0.88 ( P < 0.05), respectively, indicating that hydrogen bonds of two components significantly influenced the combination by concealing the hydrophobic amino acids and some residues, which improved PS EE and bioavailability by 3.03 and 2.84 times after PS was combined with the WPI hydrolysate. These findings are expected to enhance the absorption of PS and other macromolecules by protein enzymatic hydrolysis to broaden their applications for food.

Phytosterols are vital structural and regulatory components in plants. Zea mays produces a series of phytosterols that are specific to corn. However, the underline biosynthetic mechanism remains elusive. In this study, we identified a novel sterol methyltransferase from Z. mays (ZmSMT1-2) which showed a unique feature compared with documented plant SMTs. ZmSMT1-2 showed a substrate preference for cycloartenol. Using S-adenosyl-L-methionine (AdoMet) as a donor, ZmSMT1-2 converted cycloartenol into alkylated sterols with unique side-chain architectures, including Δ 25(27) (i.e., cyclolaudenol and cycloneolitsol) and Δ 24(25) (i.e., cyclobranol) sterols. Cycloneolitsol is identified as a product of SMTs for the first time. Our discovery provides a previously untapped mechanism for phytosterol biosynthesis and adds another layer of diversity of sterol biosynthesis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Phytosterols (PSs), a class of naturally occurring bioactive lipid compounds, have been found to possess a significant cholesterol-lowering effect. In developing countries, the consumption of rapeseed oil is the primary pathway of PS intake for the general population. However, developing low-cost, real-time, and high-throughput screening techniques for PSs remains a challenge. Here, a Cu-based nanocomposite CuOx@C was synthesized via a simple method of the calcination of HKUST-1 and systematically characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The CuOx@C demonstrated excellent peroxidase-like (POD-like) activity, functioning as a peroxidase mimic to facilitate the catalysis of 3,3',5,5'-tetramethylbenzidine (TMB) into its oxidized form (oxTMB), thereby initiating a discernible color response. On the basis of this discovery, a CuOx@C-based colorimetric method for detecting total sterols in rapeseed was successfully constructed via cascade reactions. After optimizing the conditions, the high-throughput screening of total sterols in rapeseed could be completed in only 21 min, which significantly facilitated the sensing of PSs. A linear range of 0.6-6 mg/g was achieved for the detection of total sterols in rapeseed samples, thereby satisfying the requirements for detection. In addition, due to the high stability of CuOx@C and the specificity of cholesterol oxidase, the developed method had excellent stability and selectivity toward PSs, indicating that this work has huge prospects for commercial application. This innovative work overcomes the limitation of the instrumental method and provides a portable and reliable tool for total sterols detection. It can also facilitate the development of oilseeds with a high content of PSs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Phytosterols (PS) have various beneficial effects on human health, especially the property of reducing blood cholesterol. However, the low solubility and bioaccessibility of PS have greatly limited their application in functional food ingredients., Results: To improve the bioaccessibility and stability of PS, chitosan-coated PS nanoparticles (CS-PNP) were successfully prepared by self-assembly. The properties of CS-PNP, including size, zeta potential, encapsulation efficiency (EE) and loading amount (LA) were characterised. The optimisation of CS concentration (0.4 mg mL -1 ) and pH (3.5) resulted in the formation of CS-PNP with an EE of over 90% and a particle size of 187.7 nm. Due to the special properties of CS chitosan, the interaction between CS and soybean protein isolate (SPI)/lecithin (SL) led to the formation of a soluble complex. CS-PNP exhibited good stability to temperature variations but was more sensitive to salt ions. During in vitro digestion, CS efficiently maintained the stability of nanoparticles against the hydrolysis of SPI by pepsin under acidic conditions. However, these nanoparticles tended to aggregate in a neutral intestinal environment. After 3 h of in vitro digestion, the bioaccessibility of PS increased from 18.2% of free PS to 63.5% of CS-PNP., Conclusion: Overall, these results highlight the potential of chitosan-coated nanoparticles as effective carriers for the oral administration of PS. This multilayer construction may serve as a promising for applications in food products as delivery vehicles for nutraceuticals. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The interaction of monoglycerides and phytosterols in olive- and coconut oil on the structuring of oleogels was analyzed. Specifically, bigels with gelatin hydrogel in different ratios (40:60 and 60:40 w/w) were formed. The physicochemical and microstructural attributes of these systems were assessed. The olive oil to coconut oil ratio (0-100 w/w) and the added oleogelators affected the crystal structure and the mechanical properties of the oleogels. Polarized light microscopy revealed that the addition of coconut oil created a denser triglycerides crystal network and the presence of phytosterols created more needle-like crystals, enhancing the textural properties of the oleogels and of the resulting bigels. The hardness of the oleogels ranged from 0.50 N to 1.24 N and for bigels was 5.96-36.75 N. Bigels hardness decreased as the oleogel ratio in the bigel increased. Microscopy and FTIR revealed that the addition of coconut oil in oleogels hampered the formation of a distinct crystalline monoglycerides network. Also, the absence of new peaks in the bigels indicated that the two structured phases interact with each other mostly physically, without the formation of new chemical bonds. Consequently, the oleogels and bigels developed, comprise a promising hard fat substitute with improved nutritional profile., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eugenios Katsanidis reports financial support was provided by Hellenic Foundation for Research and Innovation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Clickable chemical tools are essential for studying the localization and role of biomolecules in living cells. For this purpose, alkyne-based close analogs of the respective biomolecules are of outstanding interest. Here, in the field of phytosterols, we present the first alkyne derivative of sitosterol, which fulfills the crucial requirements for such a chemical tool as follows: very similar in size and lipophilicity to the plant phytosterols, and correct absolute configuration at C-24. The alkyne sitosterol FB-DJ-1 was synthesized, starting from stigmasterol, which comprised nine steps, utilizing a novel alkyne activation method, a Johnson-Claisen rearrangement for the stereoselective construction of a branched sterol side chain, and a Bestmann-Ohira reaction for the generation of the alkyne moiety.

Background: Myrtle ( Myrtus communis L.) is a coastal Mediterranean aromatic medicinal plant rich in essential oil components, flavonoids, and phenolic acids. Studies highlight the potential health benefits of myrtle bioactive compounds with antioxidant and antiproliferative properties. Since limited research exists on myrtle fruit's lipid fraction, the aim of this study was to apply supercritical CO 2 extraction to obtain bioactive compounds from myrtle berries focusing on the fatty acids, sterols, and essential oils., Methods: The optimization of the supercritical CO 2 extraction of myrtle fruit using CO 2 as solvent was carried out using the response surface methodology with Box-Behnken experimental design. The following conditions were tested: temperature (40, 50, and 60 °C), pressure (200, 300, and 400 bar), and flow rate (20, 30, and 40 g min -1 ) on the yield of lipid extract as well as on the yield of fatty acids, phytosterols, and volatiles present in the extract and constituting its bioactive potential., Results: In the extracts examined, 36 fatty acids, 7 phytosterols, and 13 volatiles were identified. The average yield of the extract was 5.20%, the most abundant identified fatty acid was essential cis-linolenic acid (76.83%), almost 90% of the total phytosterols were β-sitosterol (12,465 mg kg -1 ), while myrtenyl acetate (4297 mg kg -1 ) was the most represented volatile compound. The optimal process conditions obtained allow the formulation of extracts with specific compositions.

Plant sterols are minor bioactive components of food lipids, which are often used for the formulation of functional foods due to their cholesterol-lowering properties. However, they have low solubility and tend to crystallize, which may affect their biological effects, the sensory profile of the sterol-enriched food, and its consumer acceptability. Moreover, due to the unsaturated structure of sterols, they are susceptible to oxidation, so different encapsulation systems have been developed to improve their dispersibility/solubility, stability, delivery, and bioaccessibility. This chapter provides an overview of the main encapsulation systems currently used for plant sterols and their application in model and food systems, with a particular focus on their efficiency and impact on sterol bioaccessibility., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The characteristic steroid skeleton, with its 4-ringed 17-carbon structure, is one of the most recognizable organic compounds in biochemistry. In the presence of a hydroxyl ion bound to the third carbon, this structure is defined as a "sterol" (chemical formula: C 17 H 28 O). The hydroxyl group provides a hydrophilic site for the otherwise hydrophobic molecule, yielding an amphipathic lipid, which is a vital property for cellular function. It is crucial to remark that the term "steroid" describes a larger group of compounds that often retain the hydroxyl group but are primarily characterized by methyl groups, double bonds in the rings, and an aliphatic side-chain extending from the 17th carbon. In addition to serving various structural roles in the cellular membrane, sterols and steroids contribute to cellular and systemic functions as messengers, hormones, and regulators of several critical metabolic pathways.Sterol nomenclature is often confusing, partly due to structural complexity and partly due to the sheer number of different compounds that fall under the definition. Fortunately, the foremost sterols of interest in biochemistry are much fewer, and therefore, these lipids have been defined and studied vigorously. With the renaissance of lipid research during the 1990s and 2000s, many different metabolites of sterols, and more specifically phytosterols, were found to be associated with various diseases and conditions, including cardiovascular disease, hypercholesterolemia, cancer, obesity, inflammation, diabetes, and inborn errors of metabolism; thus, it is evident that the ever-evolving research in this field has been, and will continue to be, exceedingly productive.With respect to inflammation and inflammatory diseases, plant-based sterols (i.e., phytosterols) have gained considerable fame due to their anti-inflammatory and cholesterol-lowering effects demonstrated by experimental and clinical research. Besides, the exceptional pharmacological benefits of these sterols, which operate as antioxidant, antidiabetic, and anti-atherosclerotic agents, have been the subject of various investigations. While the underlying mechanisms necessitate further research, the possible function of phytosterols in improving health outcomes is an important topic to explore.In this regard, the current review aims to offer comprehensive information on the therapeutic potential of plant-based sterols in the context of human health, with a focus on preclinical effects, bioavailability, and clinical use., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Structuring liquid oils into edible oleogels from natural and abundant plant ingredients has great significance in fields ranging from foods to pharmaceuticals but has proven challenging. Herein, novel bicomponent phytosterol-based oleogels were developed with natural phenolics. Investigating diverse natural phenolics, cinnamic acid (CA) and ethyl ferulate (EF) successfully formed oleogels in combination with phytosterols (PS), where a synergistic effect on the oleogelation and crystallization was observed compared to the corresponding single component formulations. FTIR and UV-vis spectra showed that the gel network was primarily driven by hydrogen bonding and π-π stacking. Furthermore, oscillatory shear demonstrated oleogels featured higher elastic and network structure deformation at molar ratio of 5:5 and 3:7. Moreover, the bicomponent phytosterol-based oleogels displayed partially reversible shear deformation and a reversible solid-liquid transition. Such information was useful for engineering the functional properties of oleogel-based lipidic materials, providing significance for the application in foods, cosmetics and pharmaceuticals industries., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Quantification of liposoluble micronutrients in large-scale vegetable oil samples is urgently needed, because their health benefits are increasingly emphasized. However, current analytical methods are limited to either labor-intensive preparation processes or time-consuming chromatography separation. In this work, an online oil matrix separation strategy for direct, rapid, and simultaneous determination of squalene, tocopherols, and phytosterols in walnut oil (WO) was developed on the basis of the lipid class separation mode of supercritical fluid chromatography. A single run was completed in 13 min containing 6 min of column cleaning and balancing. Satisfactory limit of detections (0.05-0.20 ng/mL), limit of quantifications (0.15-0.45 ng/mL), recoveries (70.61-101.44%), and matrix effects (78.43-91.62%) were achieved, indicating the reliability of this method. In addition, eight sterol esters were identified in WO, which have not previously been reported. The proposed method was applied to characterize the liposoluble micronutrient profile of WO samples obtained from different walnut cultivars, geographical origins, and processes.

Plant sterols (PS) are cholesterol-like terpenoids widely spread in the kingdom Plantae. Being the target of extensive research for more than a century, PS have topped with evidence of having beneficial effects in healthy subjects and applications in food, cosmetic and pharmaceutical industries. However, many gaps in several fields of PS's research still hinder their widespread practical applications. In fact, many of the mechanisms associated with PS supplementation and their health benefits are still not fully elucidated. Furthermore, compared to cholesterol data, many complex PS chemical structures still need to be fully characterized, especially in oxidized PS. On the other hand, PS molecules have also been the focus of structural modifications for applications in diverse areas, including not only the above-mentioned but also in e.g., drug delivery systems or alternative matrixes for functional foods and fats. All the identified drawbacks are also superimposed by the need of new PS sources and technologies for their isolation and purification, taking into account increased environmental and sustainability concerns. Accordingly, current and future trends in PS research warrant discussion.

Over the past decades, a remarkable number of scientific studies supported the correlation between an adequate dietary intake of phytosterols (PS) and the reduced risk of cardiovascular diseases. PS are known to inhibit the intestinal absorption of cholesterol, thus promoting the reduction of the low-density lipoproteins (LDL) amount in the bloodstream. Despite the fact that a non-negligible atherogenicity was recognized to PS, thus requiring a careful risk-benefits assessment for plant sterol supplementation, the potential role of PS as cholesterol-lowering agents has been contributing to the spreading awareness of the health benefits associated with the consumption of plant-based foods. In recent years, this has been fueling the market of innovative vegetable products, such as microgreens. Surprisingly, the recent literature concerning microgreens exhibited the lack of studies focusing on the characterization of PS. To fill this gap, a validated analytical method based on the hyphenation of gas chromatography and tandem mass spectrometry is proposed here for the quantitative analysis of eight phytosterols, namely β-sitosterol, campesterol, stigmasterol, brassicasterol, isofucosterol, and cholesterol, lathosterol and lanosterol. The method was exploited for the characterization of the PS content in 10 microgreen crops, i.e., chia, flax, soybean, sunflower, rapeseed, garden cress, catalogna chicory, endive, kale and broccoli raab. Finally, these results were compared to the PS content of mature forms of kale and broccoli raab. A remarkable amount of PS was detected in chia, flax, rapeseed, garden cress, kale, and broccoli raab microgreens. 100 g (wet weight) of these microgreen crops were found to contain from 20 to 30 mg of the investigated PS. Interestingly, in the case of kale and broccoli raab microgreens, the overall PS content was higher than the one measured in the edible parts of the corresponding mature forms. Additionally, a symmetric change of the PS inner profile was observed between the two growth stages of the latter two crops. Here, the overall decrease of the PS sterol content in the mature forms was associated with the increase of the relative amount of β-sitosterol and campesterol at the expense of minor PS species, such as brassicasterol., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Phytosterols are bioactive substances naturally found in plant cell membranes, and their chemical structure is comparable to cholesterol found in mammalian cells. They are widely distributed in plant foods like olive oil, nuts, seeds, and legumes. Amongst the variety of phytosterols, stigmasterol is the vital compound found abundantly in plants. Numerous hormones, including estrogen, progesterone, corticoids and androgen, are synthesized by stigmasterol. Multiple in-vitro and in-vivo investigations have shown that stigmasterol has various biological effects, including antioxidant, anticancer, antidiabetic, respiratory diseases, and lipid-lowering effects. Experimental research on stigmasterol provides indisputable proof that this phytosterol has the potential to be employed in supplements used to treat the illnesses mentioned above. This substance has a high potential, making it a noteworthy medication in the future. Although several researchers have investigated this phytosterol to assess its prospective qualities, it has not yet attained therapeutic levels, necessitating additional clinical studies. This review offers a comprehensive update on stigmasterol, including chemical framework, biosynthesis, synthetic derivatives, extraction and isolation, analytical aspects, pharmacological profile, patent status, clinical trials, stability and specifications as per regulatory bodies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Daily intake of phytosterols (PSs) as a diet supplement can lower blood-cholesterol levels and reduce the risks of cardiovascular diseases. However, the high crystallinity, low water solubility, easy oxidizability, and other characteristics of PSs restrict their application and bioavailability in food products. The formulation parameters including the structures of PSs, delivery carriers, and food matrices may play an important role in the release, dissolution, transport, and absorption of PSs in functional foods. In this paper, the effects of formulation parameters, including phytosterol structures, delivery carriers, and food matrices, on the bioavailability of phytosterols are summarized and suggestions are provided for the formulation design of functional foods. The side chain and hydroxyl esterification group of PSs may significantly affect their lipid or water solubilities and micellization capacities, which in turn affect the bioavailability of PSs. Selecting suitable delivery carriers based on the characteristics of the food system can reduce the crystallinity and oxidation of PSs and control the release of PSs, thereby improving the PS stability and delivery efficiency. Moreover, the ingredients of the carriers or food products would also influence the release, solubility, transport, and absorption of PSs in the gastrointestinal tract (GIT).

Cholesterol is the precursor of bioactive plant metabolites such as steroidal saponins. An Australian plant, Dioscorea transversa, produces only two steroidal saponins: 1β-hydroxyprotoneogracillin and protoneogracillin. Here, we used D. transversa as a model in which to elucidate the biosynthetic pathway to cholesterol, a precursor to these compounds. Preliminary transcriptomes of D. transversa rhizome and leaves were constructed, annotated, and analyzed. We identified a novel sterol side-chain reductase as a key initiator of cholesterol biosynthesis in this plant. By complementation in yeast, we determine that this sterol side-chain reductase reduces Δ 24,28 double bonds required for phytosterol biogenesis as well as Δ 24,25 double bonds. The latter function is believed to initiate cholesterogenesis by reducing cycloartenol to cycloartanol. Through heterologous expression, purification, and enzymatic reconstitution, we also demonstrate that the D. transversa sterol demethylase (CYP51) effectively demethylates obtusifoliol, an intermediate of phytosterol biosynthesis and 4-desmethyl-24,25-dihydrolanosterol, a postulated downstream intermediate of cholesterol biosynthesis. In summary, we investigated specific steps of the cholesterol biosynthetic pathway, providing further insight into the downstream production of bioactive steroidal saponin metabolites., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Hydrophilic phytosterol glycosyl derivatives are synthetic phytosterol analogues by coupling with the glycosyl moiety to improve the water solubility and bioaccessibility of free phytosterols. The aim of this study is to clarify the molecular interaction of phytosterol glycosyl derivatives with bile salts and the consequent impact on cholesterol solubilization. Sharp nonlinear decrease in the micellar solubility of cholesterol and accompanying changes in particle size, zeta potential and microtopography of mixed micelles were observed when phytosterol glycosyl derivatives were introduced in cholesterol-loaded bile salt micelles. These results suggested that β-sitosterol glycosyl derivatives molecules indeed participated in the formation of mixed micelles. Further, nuclear magnetic resonance showed that the structural change of mixed micelles was caused by the insertion of β-sitosterol glycosyl derivatives via hydrogen bonds with sodium taurocholate, which resulted in the low cholesterol solubilization. Moreover, the hydrogen-bond interactions were apparently influenced by the glycosyl moiety of β-sitosterol glycosyl derivatives. These molecular mechanisms may contribute to the development of cholesterol-absorption inhibitors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The formulation of phytosterol (PS)-enriched functional foods has attracted increasing interest in the recent years, owing to its potential health effects. However, the poor solubility and bioavailability greatly limit PS application in this regard. This study investigated whether soy protein isolate (SPI) could effectively perform as a nanocarrier for improving the water solubility, bioaccessibility, and cholesterol-lowering activity of PSs., Results: In this work, we fabricated SPI-PS nanocomplexes, which not only can enhance the stability and bioaccessibility of PS, but also improve the cholesterol-lowering ability of SPI. This improvement was mainly due to the formation of protein-active substance complexes, through hydrophobic interactions. The complexation with PSs resulted in formation of nanosized particles with greater sizes, lower ζ-potential, and higher surface hydrophobicity. The encapsulation efficiency, loading amount, and solubility of PS were closely related to the applied PS concentration in the mixed dispersions, and the maximal PS solubility in the aqueous phase reached about 1.63 mg mL -1 at the highest PS concentration (2.0 mg mL -1 ). The PS molecules in the nanocomplexes were mainly present in the amorphous form. The enhanced in vitro cholesterol-lowering activity of PS nanocomplexes relative to free PS seemed to be closely related to its higher bioaccessibility., Conclusion: The findings are of relevance for the development of food-grade PS ingredients suitable for the formulations of PS-enriched functional foods. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Background: Oleogels represent one of the most important carriers for the delivery of lipophilic nutraceuticals. Phytosterols (PS), plant-derived natural sterol compounds, are preferred for oleogel preparation due to their self-assembly properties and health function. However, the relationship between the physical properties of PS-based oleogels and the chemical stability of loaded bioactive compounds is still unclear., Results: The influence of lecithin (LC) and glycerol monostearate (GMS) on the physical properties of PS-based oleogels made of liquid coconut oil and the stability of curcumin as a model bioactive loaded in the oleogels was investigated. Results showed that the flow consistency index was much higher for GMS-containing oleogels than that for LC-containing oleogels. The optical microscopy and X-ray scattering analysis showed that the addition of GMS in the PS oleogels promoted the formation of a crystal mixture with different crystal polymorph structures, whereas LC addition promoted the formation of needle-like crystals of PS. Using curcumin as a model lipophilic nutraceutical, the GMS-enriched PS oleogels with high crystallinity and flow consistency index exhibited a good retention ratio and scavenging activity of the loaded curcumin when stored at room temperature., Conclusion: This study shows that enhancing the firmness of oleogels made from PS and liquid coconut oil is beneficial to the retention and chemical stability of a loaded bioactive (curcumin). The findings of the study will boost the development of PS-based oleogel formulations for lipophilic nutraceutical delivery. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Background: α-Lipoic acid has excellent antioxidant activity, but its poor lipid solubility greatly limits its practical application. This study was undertaken (i) to develop a novel and efficient enzymatic synthesis of lipophilic lipoic acid esters using Candida sp. 99-125 lipase as a catalyst; and (ii) to systematically evaluate their antioxidant potential against bulk oil, oil-in-water emulsion (O/W) and cooked ground meat., Results: Lipophilic lipoic acid esters were successfully and efficiently synthesized using phytosterols as acyl receptor in the presence of Candida sp. 99-125 lipase. The product was identified as phytosterol lipoate by mass spectrometry, Fourier transform infrared spectroscopy and nuclear magnetic resonance. The maximum conversion of phytosterol lipoate surpassed 90% within 12 h and its final yield exceeded 81%. Interestingly, the oil solubility of lipoic acid was increased at least 25-fold and other physicochemical properties were significantly improved. Most importantly, phytosterol lipoate exhibited higher antioxidant activity than lipoic acid in bulk oil, O/W emulsions and cooked ground meat., Conclusion: The antioxidant capacity of lipoic acid can be significantly enhanced by esterification with phytosterols. Therefore, phytosterol lipoate could be further developed as a new antioxidant for use in oil- and fat-based foods. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Animal fat as the key component of sensory experience impacts texture, juiciness, and aroma pleasantness of meat, which indicates the necessity of designing fat mimetics in meat alternatives. In this study, high internal phase emulsions (HIPE) with tunable flavor release as fat mimetics based on glycyrrhizic acid (GA) and phytosterol were prepared, and the effects of GA and phytosterol concentrations on the microstructural, rheological, and flavor release properties of HIPE were evaluated. Phytosterol crystals-enriched oil droplets were trapped inside the GA fibrillar matrix as stabilizers. HIPE containing higher GA and phytosterol concentrations exhibited smaller droplet size and better viscoelastic attributes. Additionally, phytosterol played a synergistic role with GA to form a double-fiber microstructure at the oil-water interface. This hierarchical microstructure of oil phase, interface and aqueous phase in the HIPE could regulate the release of hydrophilic and lipophilic meat volatiles. HIPE as fat mimetics with unique microstructure have potential applications in meat alternatives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The study investigated the thermo-oxidative stability of distigmasterol-modified acylglycerols as a new structured acylglycerols. Samples were heated at 60 and 180 °C for 8 h. Their percentage degradation and products formed during heating were compared with free stigmasterol and stigmasteryl esters. The remaining of stigmasterol and fatty acid parts, the formation of stigmasterol oxidation products and the composition of polar and non-polar fractions were analysed using chromatographic methods. The cytotoxicity and genotoxicity were determined with the use of an MTT test and a comet assay, respectively. The highest stability during heating was observed for 2,3-distigmasterylsuccinoyl-1-oleoyl-sn-glycerol (dStigS-OA) and the lowest for 2,3-distigmasterylcarbonoyl-1-oleoyl-sn-glycerol (dStigC-OA). Data showed that the formation of thermo-oxidative degradation products is affected by the temperature and chemical structure of lipids present in the molecule. The dStigMAs bonded by a succinate linker and products formed during their thermo-oxidation showed no cytotoxic or genotoxic activity to normal human cells., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Phytosterols were analyzed in 34 different quinoa accessions, which were obtained from the same field trial. Twenty different sterols were detected, and 17 could be structurally assigned by means of gas chromatography with mass spectrometry. Sterols were quantitated in selected ion monitoring mode (GC/MS-SIM) with the novel internal standard 3- O - tert -butyldimethylsilyl-cholestanol (cholestanyl-TBDMS). GC/MS-SIM response factors of minor sterols were determined after enrichment by countercurrent chromatography. The total sterol contents varied from 120 to 180 mg/100 g of seeds, which is higher than has been described in quinoa before. This was due to the fact that Δ7-sterols (e.g., Δ7-sitosterol, spinasterol, and Δ7-avenasterol) were quantitated for the first time in quinoa and contributed ∼64% to the total sterol content. Clustering allowed distributing of the 34 different quinoa accessions into four distinct groups on the basis of the different sterol patterns.

The impact of photosensitizer and wavelength on photooxidation of phytosterols (PS) in soymilk and the oxidative stability of lipid and protein was determined. The oxidation of lipid and the consumption of dissolved oxygen showed a close relationship with PS oxidation. Riboflavin (Rb) leads to extra oxidation of both lipid and protein, and chlorophyll (Chl) prefer to absorb to and change the structure of protein. The influence of Rb and Chl on PS degradation under different wavelengths of light in the range of 365-665 nm was measured. Original soymilk emulsion placed under UVA (365-375 nm) and violet (400-410 nm) light underwent the most PS deterioration, whereas riboflavin was responsible for oxidation around blue (465-475 nm) region and extra formation of 6β-OH sterols, and chlorophyll enriched emulsion was vulnerable under red (645-665 nm) light. The wavelength of light (UVA > violet > blue > green > red > yellow) showed a great different effect in oxidation of PS and formation of phytosterol oxidation products (POPs). The UVA, violet, blue and red light gives rise to the prior five kind oxides of phytosterol: 6α-OH, 7α-OH, 7β-OH, 5,6β-epoxy and 7-keto., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The feasibility of using saponification coupled to extraction with mixed micellar systems to recover bioactive compounds from soybean oil deodorizer distillate, was evaluated for the first time. Under the selected conditions, saponification with KOH 0.6 M and aqueous micellar system prepared with Tergitol 15-S-7 9% w/w, rhamnolipids 0.25 %w/w and sodium citrate 100 mM pH 5.00, at 65 °C, allow the recovery of almost 100% of α- and δ- tocopherols, and 90% of γ-tocopherols. LC-MS measurements demonstrated that the final extract also contained phytosterols and squalene. Additionally, the obtained extract preserved about 100% of the total antioxidant activity. This result was attributable to the fact that 93% of the tocopherols recovered in the micellar phases resulted to be associated with surfactant micelles, environment that is known to improve their antioxidant capacity. These results open perspectives to the use of this methodology to extract these valuable compounds from complex oily sources., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

New carriers of phytosterols; acylglycerols containing natural myristic acid at sn -1 and sn -3 positions and stigmasterol residue linked to sn -2 position by carbonate and succinate linker have been designed and synthesized in three-step synthesis from dihydroxyacetone (DHA). The synthetic pathway involved Steglich esterification of DHA with myristic acid; reduction of carbonyl group of 1,3-dimyristoylpropanone and esterification of 1,3-dimyristoylglicerol with stigmasterol chloroformate or stigmasterol hemisuccinate. The structure of the obtained hybrids was established by the spectroscopic methods (NMR; IR; HRMS). Obtained hybrid molecules were used to form new liposomes in the mixture with model phospholipid and their effect on their physicochemical properties was determined, including the polarity, fluidity, and main phase transition of liposomes using differential scanning calorimetry and fluorimetric methods. The results confirm the significant effect of both stigmasterol-containing acylglycerols on the hydrophilic and hydrophobic region of liposome membranes. They significantly increase the order in the polar heads of the lipid bilayer and increase the rigidity in the hydrophobic region. Moreover, the presence of both acylglycerols in the membranes shifts the temperature of the main phase transition towards higher temperatures. Our results indicate stabilization of the bilayer over a wide temperature range (above and below the phase transition temperature), which in addition to the beneficial effects of phytosterols on human health makes them more attractive components of novel lipid nanocarriers compared to cholesterol.

Androstenedione (AD) is a key intermediate in the body's steroid metabolism, used as a precursor for several steroid substances, such as testosterone, estradiol, ethinyl estradiol, testolactone, progesterone, cortisone, cortisol, prednisone, and prednisolone. The world market for AD and ADD (androstadienedione) exceeds 1000 tons per year, which stimulates the pharmaceutical industry's search for newer and cheaper raw materials to produce steroidal compounds. In light of this interest, we aimed to investigate the progress of AD biosynthesis from phytosterols by prospecting scientific articles (Scopus, Web of Science, and Google Scholar databases) and patents (USPTO database). A wide variety of articles and patents involving AD and phytosterol were found in the last few decades, resulting in 108 relevant articles (from January 2000 to December 2021) and 23 patents of interest (from January 1976 to December 2021). The separation of these documents into macro, meso, and micro categories revealed that most studies (articles) are performed in China (54.8%) and in universities (76%), while patents are mostly granted to United States companies. It also highlights the fact that AD production studies are focused on "process improvement" techniques and on possible modifications of the "microorganism" involved in biosynthesis (64 and 62 documents, respectively). The most-reported "process improvement" technique is "chemical addition" (40%), which means that the addition of solvents, surfactants, cofactors, inducers, ionic liquids, etc., can significantly increase AD production. Microbial genetic modifications stand out in the "microorganism" category because this strategy improves AD yield considerably. These documents also revealed the main aspects of AD and ADD biosynthesis: Mycolicibacterium sp. (basonym: Mycobacterium sp.) (40%) and Mycolicibacterium neoaurum (known previously as Mycobacterium neoaurum ) (32%) are the most recurrent species studied. Microbial incubation temperatures can vary from 29 °C to 37 °C; incubation can last from 72 h to 14 days; the mixture is agitated at 140 to 220 rpm; vegetable oils, mainly soybean, can be used as the source of a mixture of phytosterols. In general, the results obtained in the present technological prospecting study are fundamental to mapping the possibilities of AD biosynthesis process optimization, as well as to identifying emerging technologies and methodologies in this scenario.

Phytosterols are natural plant-based bioactive compounds that can lower blood cholesterol levels and help prevent cardiovascular diseases. Consequently, they are being utilized in functional foods, supplements, and pharmaceutical products designed to improve human health. This paper summarizes different approaches to isolate, purify, and characterize phytosterols. It also discusses the hypolipidemic mechanisms of phytosterols and their impact on cholesterol transportation. Phytosterols have a low water-solubility, poor chemical stability, and limited bioavailability, which limits their utilization and efficacy in functional foods. Strategies are therefore being developed to overcome these shortcomings. Colloidal delivery systems, such as emulsions, oleogels, liposomes, and nanoparticles, have been shown to be effective at improving the water-dispersibility, stability, and bioavailability of phytosterols. These delivery systems can be used to incorporate phytosterols into a broader range of cholesterol-lowering functional foods and beverages. We also discuses several issues that need to be addressed before these phytosterol delivery systems can find widespread commercial utilization.

Phytosterols have received an extensive attention owing to their excellent cholesterol-lowering activity and the role in cardiovascular diseases prevention. Phytosterol diacid monoesters, the important intermediates in the structural modification of free phytosterols, were usually obtained by chemical method with catalyst. The aim of this research was to provide an eco-friendly approach for the preparation of phytosterol diacid monoester and explore the possible mechanism of their hypocholesteremic effect using model bile mixed micelles. Catalyst-free synthesis of β-sitosterol with succinic anhydride, maleic anhydride, and glutaric anhydride was investigated and optimized. The yields of three β-sitosterol diacid monoesters all reached above 94% under optimum reaction conditions and their chemical structures were confirmed further by mass spectroscopy, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy. Compared with β-sitosterol, β-sitosterol diacid monoesters possessed the increased thermal stability (up to an above 355.28°C) and improved solubility in binary mixed micelle system (exceeding 1.7 mM) and similar cholesterol-lowering activity (7.78%-11.05%). Moreover, β-sitosterol diacid monoesters showed the competitive effect on solubilization of cholesterol due to their enhanced micellar incorporation capacity. Overall, the competition with cholesterol in vitro gives useful information about the cholesterol-lowering activity of phytosterol diacid monoesters, which will further expand their applications in the food industry and health. PRACTICAL APPLICATION: Modified phytosterols, phytosterol diacid monoesters, were successfully synthesized in petroleum ether without catalyst. These products enhanced the thermal stability of free phytosterols and reduced the dissolution capacity of cholesterol in model bile mixed micelles due to competitive solubilization. These results indicated that phytosterol diacid monoesters represented cholesterol-lowering potential, which might further expand the applications in the food industry and health., (© 2022 Institute of Food Technologists®.)

Coffee silverskin is a byproduct of the coffee roasting process contributing to organic waste burdens in urban areas. Silverskin is a potential source of dietary fiber, protein, carbohydrates, caffeine as well as vitamins and minerals. However, phytosterols present in the plant are susceptible to thermal oxidation resulting in the formation of phytosterol oxidation products (POPs) in the silverskin during roasting. In collaboration with a small roastery, the formation of POPs in three coffee varieties with roasting time was monitored by GC-MS. The objective was to evaluate the safety and potential benefits of incorporating coffee silverskin into value-added products. The qualitative profile of POPs in the silverskin from the three varieties was similar. Average total POPs were 0.32 g POPs/kg silverskin. POPs from the dominant plant sterol, sitosterol, were present at the highest concentrations. Caffeine, total antioxidant capacity, and total flavonoids were measured in the silverskin of the three coffees. Average values were 1.3 g caffeine/100 g silverskin, TEAC of 11 mmol Trolox/kg silverskin, and 1.94 to 8.60 mg catechin equivalent (CE)/g silverskin, respectively. An analysis of the impact of consuming teas and baked goods containing silverskin was also performed. Using published formulations, a tea or cookie containing silverskin would contribute approximately 1 and 0.3 mg POP per day, respectively. Consumption of these products would not substantially increase dietary exposure to POPs, while increasing fiber and antioxidants while reducing organic waste. PRACTICAL APPLICATION: Coffee silverskin has been studied as a possible source of fiber, antioxidants, and caffeine when incorporated in snack foods and used to make teas. To assess possible concerns about increasing dietary oxidized phytosterols, the formation of phytosterol oxidation products (POPs) was investigated in the silverskin fraction during the roasting process in three coffee varieties. In addition, caffeine, antioxidant capacity, and total flavonoids were determined. We found that silverskin can be safely used for value-added products including caffeinated teas, cookies, and bars with minimal impact on dietary POP exposures., (© 2022 Institute of Food Technologists®.)

The stem bark of Ancistrocarpus densispinosus Oliv. exhibited triterpenoids, including the rare fernane-type, fern-9(11)-ene-2α,3β-diol ( 1 ) a possible chemotaxonomically distinct biomolecule for the genus. Other triterpenoids that were isolated from this plant include the ursane-type ursolic acid ( 2 ) and corosolic acid ( 3 ), friedelane-type friedelin ( 4 ) and canophyllol ( 5 ), lupane-type lupeol ( 6 ), betulin ( 7 ), betulinic acid ( 8 ) and hennadiol ( 9 ), oleanoic acid ( 10 ), maslinic acid ( 11 ) and taraxerol ( 12 ) and three sterols. This is the first report of the chemistry of a plant of the Ancistrocarpus . The structures of the compounds were elucidated based on their NMR, IR and MS techniques and by comparisons of their experimental data with those reported. The twelve triterpenoids 1 - 12 were found to be inactive against five bacterial strains Escherichia coli, Bacillus subtilis, Pseudomonas agarici, Micrococcus luteus and Staphylococcus warneri; inactive against KB-3-1 cervix carcinoma cancer cell line and inactive as antioxidants in the DPPH assay.

Fresh and processed food products are rich in bioactive molecules, including polysaccharides, vitamins, carotenoids, peptides, antioxidants, phenolics, phytosterols, and novel lipids. Bioactive molecules in food could prevent several diseases (i.e., metabolic syndrome, cardiovascular diseases, cancer, etc.). Thus, consumer awareness is growing about the health-promoting impact of food bioactive molecules. Health claims are essential added-value features, wherein health-enhancing potential of bioactives depend on their chemical structure. On the other hand, the investigation of the structure-function relationship of food bioactive molecules is of importance. In this regard, Molecules is delighted to highlight the importance of food bioactive molecules and their effect on health. In this Special Issue of Molecules, researchers are invited to contribute original research and up-to-date reviews.

Mandarin is a favorite fruit of the citrus family. Mandarin seeds are considered a source of nontraditional oil obtained from byproduct materials. This investigation aimed to assess the biomolecules of mandarin seeds and evaluated their antimycotic and antimycotoxigenic impact on fungi. Moreover, it evaluated the protective role of mandarin oil against aflatoxin toxicity in cell lines. The two types of extracted oil (fixed and volatile) were ecofriendly. The fatty acid composition, tocopherol, sterols, and carotenoids were determined in the fixed oil, whereas volatiles and phenolics were estimated in the essential oil. A mixture of the two oils was prepared and evaluated for its antimicrobial impact. The reduction effect of this mixture was also investigated to reduce mycotoxin secretion using a simulated experiment. The protective effect of the oil was evaluated using healthy strains of cell lines. Fixed oil was distinguished by the omega fatty acid content (76.24%), lutein was the major carotenoid (504.3 mg/100 g) and it had a high β -sitosterol content (294.6 mg/100 g). Essential oil contained limonene (66.05%), α -pinene (6.82%), β -pinene (4.32%), and γ -terpinene (12.31%) in significant amounts, while gallic acid and catechol were recorded as the dominant phenolics. Evaluation of the oil mix for antimicrobial potency reflected a considerable impact against pathogenic bacteria and toxigenic fungi. By its application to the fungal media, this oil mix possessed a capacity for reducing mycotoxin secretion. The oil mix was also shown to have a low cytotoxic effect against healthy strains of cell lines and had potency in reducing the mortality impact of aflatoxin B 1 applied to cell lines. These results recommend further study to involve this oil in food safety applications.

RCE-4, a steroidal saponin isolated from Reineckia carnea , has been studied previously and has exhibited promising anti-cervical cancer properties by inducing programmed cell death (PCD) of Ca Ski cells. Considering the cancer cells developed various pathways to evade chemotherapy-induced PCD, there is, therefore, an urgent need to further explore the potential mechanisms underlying its actions. The present study focused on targeting the Bcl-2-Beclin 1 complex, which is known as the key regulator of PCD, to deeply elucidate the molecular mechanism of RCE-4 against cervical cancer. The effects of RCE-4 on the Bcl-2-Beclin 1 complex were investigated by using the co-immunoprecipitation assay. In addition, autophagy-related genes (ATG) were also analyzed due to their special roles in PCD. The results demonstrated that RCE-4 inhibited the formation of the Bcl-2-Beclin 1 complex in Ca Ski cells via various pathways, and ATG 4B proteins involved in this process served as a key co-factor. Furthermore, based on the above, the sensitivity of RCE-4 to Ca Ski cells was significantly enhanced by inhibiting the expression of the ATG 4B by applying the ATG 4B siRNA plasmid.

Plant sterols, also referred as phytosterols, have been known as bioactive compounds which have cholesterol-lowering properties in human blood. It has been established that a diet rich in plant sterols or their esters alleviates cardiovascular diseases (CVD), and also may inhibit breast, colon and lung carcinogenesis. Phytosterols, in their free and esterified forms, are prone to thermo-oxidative degradation, where time and temperature affect the level of degradation. Looking for new derivatives of phytosterols with high thermo-oxidative stability for application in foods, our idea was to obtain novel structured acylglycerols in which two fatty acid parts are replaced by stigmasterol residues. In this work, asymmetric (1,2- and 2,3-) distigmasterol-modified acylglycerols (dStigMAs) were synthesized by the covalent attachment of stigmasterol residues to sn -1 and sn -2 or sn -2 and sn -3 positions of 3-palmitoyl- sn -glycerol or 1-oleoyl- sn -glycerol, respectively, using a succinate or carbonate linker. The chemical structures of the synthesized compounds were identified by NMR, HR-MS, and IR data. Moreover, the cytotoxicity of the obtained compounds was determined. The dStigMAs possessing a carbonate linker showed potent cytotoxicity to cells isolated from the small intestine and colon epithelium and liver, whereas the opposite results were obtained for compounds containing a succinate linker.

Phytosterols constitute a class of natural products that are an important component of diet and have vast applications in foods, cosmetics, and herbal medicines. With many and diverse isolated structures in nature, they exhibit a broad range of biological and pharmacological activities. Among over 200 types of phytosterols, stigmasterol and β-sitosterol were ubiquitous in many plant species, exhibiting important aspects of activities related to neurodegenerative diseases. Hence, this mini-review presented an overview of the reported studies on selected phytosterols related to neurodegenerative diseases. It covered the major phytosterols based on biosynthetic considerations, including other phytosterols with significant in vitro and in vivo biological activities.

Dysoxylum tpongense Pierre (local name 'Huynh Dan Bap') belonging to family Meliaceae, is a tree (3-10 m height), distributed in the mountainous areas (ca. 1000 m a.s.l.) in North Vietnam. From the dichloromethane fraction of the methanol extract of the leaves and stems of this plant, six dammarane triterpenes, one furanoid diterpene together with three sterols were isolated. Evaluation of biological activities of isolated compounds showed that cabraleahydroxylactone (5), cabraleahydroxylactone 3-acetate (6), and stigmast-4-en-3-one (10) possessed an anti-inflammatory effect against Liver X receptor (LXR) activation in HepG2 cell line model with IC 50 values of 20.29 ± 3.69, 24.32 ± 2.99, and 7.09 ± 0.97 (μM), respectively. While three other triterpenoid compounds aglinin C 3- acetate (1), aglinin C (2), and 24-epi-cabraleadiol (4) presented the most significant inhibitory effect against TNF-α induced NF-κB activation in HepG2 cell line in a dose-dependent manner with IC 50 values of 12.45 ± 2.37, 23.32 ± 3.25, and 13.95 ± 1.57 μM, respectively. As stigmast-4-en-3-one (10), with structure closely similar to cholesterol, acted selectively on LXRs but not on NF-kB activation pathway, this suggests that stigmast-4-en-3-one (10) can be potentially applied as an agonist on LXR signaling pathway. Pathways LXRs-NF-κB-iNOS expression have a close relationship and play a crucial role in proceeding metabolic abnormalities like atherosclerosis, obesity, inflammation, etc. Thus, the findings showed that dammarane-type triterpenoids from D. tpongense are worthy of further investigation for potential LXR agonists and potent anti-atherogenic agents against atherosclerotic lesion progression., (Copyright © 2021 Elsevier Inc. All rights reserved.)