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1.
Environ Sci Pollut Res Int ; 31(39): 51870-51882, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39134796

ABSTRACT

The study investigated the effects of cultivating Tridax procumbens in hydroponic conditions with different concentrations of copper ions, aiming to understand the physiological changes and the impact on the biosynthesis of secondary metabolites. The treatments consisted of a completely randomized design, with five increasing concentrations of copper (T0 = 0.235, T1 = 12.5, T2 = 25, T3 = 50, T4 = 100 µmol L-1 of Cu), under controlled conditions for 36 days. Analysis of bioactive compounds in leaves was performed by HPLC-DAD and ESI-MS. Several phenolic compounds, alkaloids, phytosterols and triterpenoids were identified, demonstrating the plant's metabolic plasticity. The highest dose of copper (100 µmol L-1) significantly promoted voacangine, the most predominant compound in the analyses. Notably, 66.7% of the metabolites that showed an increase in concentration, were phenolic compounds. Furthermore, treatments with 12.5 and 25 µmol L-1 of copper were identified as promoting the biosynthesis of phytosterols and triterpenoids. These biochemical adaptations can play a fundamental role in the survival and development of plants in environments contaminated by metals, and from this it is possible to determine cultivation techniques that maximize the biosynthesis of the compound of interest.


Subject(s)
Copper , Plant Leaves/metabolism , Asteraceae/metabolism , Phytosterols/metabolism
2.
Crit Rev Food Sci Nutr ; 64(21): 7426-7450, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39093582

ABSTRACT

The health benefits of nut consumption have been extensively demonstrated in observational studies and intervention trials. Besides the high nutritional value, countless evidences show that incorporating nuts into the diet may contribute to health promotion and prevention of certain diseases. Such benefits have been mostly and certainly attributed not only to their richness in healthy lipids (plentiful in unsaturated fatty acids), but also to the presence of a vast array of phytochemicals, such as polar lipids, squalene, phytosterols, tocochromanols, and polyphenolic compounds. Thus, many nut chemical compounds apply well to the designation "nutraceuticals," a broad umbrella term used to describe any food component that, in addition to the basic nutritional value, can contribute extra health benefits. This contribution analyses the general chemical profile of groundnut and common tree nuts (almond, walnut, cashew, hazelnut, pistachio, macadamia, pecan), focusing on lipid components and phytochemicals, with a view on their bioactive properties. Relevant scientific literature linking consumption of nuts, and/or some of their components, with ameliorative and/or preventive effects on selected diseases - such as cancer, cardiovascular, metabolic, and neurodegenerative pathologies - was also reviewed. In addition, the bioactive properties were analyzed in the light of known mechanistic frameworks.


Subject(s)
Dietary Supplements , Juglans , Nuts , Phytochemicals , Pistacia , Nuts/chemistry , Phytochemicals/analysis , Phytochemicals/pharmacology , Humans , Dietary Supplements/analysis , Juglans/chemistry , Pistacia/chemistry , Lipids/analysis , Nutritive Value , Anacardium/chemistry , Macadamia/chemistry , Corylus/chemistry , Phytosterols/analysis , Carya/chemistry , Prunus dulcis/chemistry , Cardiovascular Diseases/prevention & control
3.
Lifestyle Genom ; 17(1): 82-92, 2024.
Article in English | MEDLINE | ID: mdl-38952113

ABSTRACT

INTRODUCTION: This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. METHODS: Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. RESULTS: FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. CONCLUSION: The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.


Subject(s)
Diet, High-Fat , Linoleic Acids, Conjugated , Lipid Metabolism , Liver , PPAR alpha , Sterol Regulatory Element Binding Protein 1 , Triglycerides , Animals , Diet, High-Fat/adverse effects , Mice , Male , Triglycerides/metabolism , Liver/metabolism , Liver/drug effects , Lipid Metabolism/drug effects , PPAR alpha/metabolism , PPAR alpha/genetics , Sterol Regulatory Element Binding Protein 1/metabolism , Sterol Regulatory Element Binding Protein 1/genetics , Linoleic Acids, Conjugated/pharmacology , Lipogenesis/drug effects , Carnitine O-Palmitoyltransferase/metabolism , Carnitine O-Palmitoyltransferase/genetics , Uncoupling Protein 2/metabolism , Uncoupling Protein 2/genetics , Phytosterols/pharmacology , Adipose Tissue/metabolism , Adipose Tissue/drug effects , Weight Gain/drug effects , Lipoprotein Lipase/metabolism , Lipoprotein Lipase/genetics
4.
Chem Biodivers ; 21(9): e202400686, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38923804

ABSTRACT

Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (ß-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 ß-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 ß-SIT showed toxicity up to 25 µg/mL. PHEX inhibited 66 % of nitric oxide radicals, while STIG and ß-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 ß-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity.


Subject(s)
Anti-Inflammatory Agents , Larva , Nitric Oxide , Stigmasterol , Animals , Larva/drug effects , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Stigmasterol/pharmacology , Stigmasterol/chemistry , Stigmasterol/isolation & purification , Nitric Oxide/metabolism , Nitric Oxide/antagonists & inhibitors , Sitosterols/pharmacology , Sitosterols/chemistry , Cell Line , Phytosterols/pharmacology , Phytosterols/chemistry , Cell Survival/drug effects , Dose-Response Relationship, Drug , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/isolation & purification
5.
Steroids ; 209: 109453, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38901661

ABSTRACT

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 Fsp3-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.


Subject(s)
Antifungal Agents , Candida , Molecular Docking Simulation , Phytosterols , Triterpenes , Triterpenes/chemistry , Triterpenes/pharmacology , Triterpenes/isolation & purification , Candida/drug effects , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Ligands , Phytosterols/chemistry , Phytosterols/pharmacology , Phytosterols/isolation & purification , Molecular Dynamics Simulation , Microbial Sensitivity Tests , Ursolic Acid
6.
Sci Rep ; 14(1): 11108, 2024 05 15.
Article in English | MEDLINE | ID: mdl-38750162

ABSTRACT

Phytosterols are natural components of plant-based foods used as supplements because of their known cholesterol-lowering effect. However, their effects on lipoprotein subfractions and the quality of the LDL particle have not been studied in greater detail. We aimed to evaluate the effects of phytosterols supplements on lipids, lipoproteins subfractions, and on the quality of LDL. A prospective, pilot-type, open label, cross-over study, randomized 23 males in primary prevention of hypercholesterolemia to receive diet or diet plus phytosterol (2.6 g in 2 doses, with meals) for 12 weeks, when treatments were switched for another 12 weeks. Lipoprotein subfractions were analyzed by electrophoresis in polyacrylamide gel (Lipoprint System®). The Sampson equation estimated the small and dense (sd) and large and buoyant (lb) LDL subfractions from the lipid profile. Quality of LDL particle was analyzed by Z-scan and UV-vis spectroscopy. Primary outcome was the comparison of diet vs. diet plus phytosterols. Secondary outcomes assessed differences between baseline, diet and diet plus phytosterol. Non-parametric statistics were performed with p < 0.05. There was a trend to reduction on HDL-7 (p = 0.05) in diet plus phytosterol arm, with no effects on the quality of LDL particles. Heatmap showed strong correlations (ρ > 0.7) between particle size by different methods with both interventions. Diet plus phytosterol reduced TC, increased HDL-c, and reduced IDL-B, whereas diet increased HDL7, and reduced IDL-B vs. baseline (p < 0.05, for all). Phytosterol supplementation demonstrated small beneficial effects on HDL-7 subfraction, compared with diet alone, without effects on the quality of LDL particles.This trial is registered in Clinical Trials (NCT06127732) and can be accessed at https://clinicaltrials.gov .


Subject(s)
Cross-Over Studies , Dietary Supplements , Hypercholesterolemia , Phytosterols , Phytosterols/pharmacology , Phytosterols/administration & dosage , Humans , Male , Middle Aged , Hypercholesterolemia/diet therapy , Hypercholesterolemia/blood , Hypercholesterolemia/drug therapy , Lipoproteins, LDL/blood , Prospective Studies , Adult , Cholesterol, LDL/blood , Pilot Projects , Lipoproteins/blood
7.
Clin Investig Arterioscler ; 36(4): 229-233, 2024.
Article in English, Spanish | MEDLINE | ID: mdl-38443216

ABSTRACT

Sitosterolemia is an autosomal recessive and very rare disease. Its main characteristic is that there is a greater absorption and a decrease in the excretion of sterols, which leads to them being deposited in tissues. It is given by mutations in the ABCG5 or ABCG8 genes found on chromosome 2p21. In this clinical note, we describe the first two patients with familial sitosterolemia described in Colombia, brothers, one of them with xanthomas in extremities as the only symptom, and the other, completely asymptomatic. Genetic studies were performed as a diagnostic test in both patients, where a pathogenic homozygous variant could be identified in the ABCG8 gene in the first case (symptomatic), and a heterozygous variant in the ABCG8 gene in the second case (asymptomatic); the first patient has responded to treatment with ezetimibe. In conclusion, xanthomas should be studied in depth in pediatric age as they may be the only visible sign of such complex and hereditary diseases as familial sitosterolemia, which can be controlled and prevent cardiovascular complications of the disease.


Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 8 , Ezetimibe , Hypercholesterolemia , Intestinal Diseases , Lipid Metabolism, Inborn Errors , Phytosterols , Humans , Lipid Metabolism, Inborn Errors/genetics , Lipid Metabolism, Inborn Errors/diagnosis , Male , Colombia , Phytosterols/adverse effects , Phytosterols/genetics , Intestinal Diseases/genetics , Intestinal Diseases/diagnosis , ATP Binding Cassette Transporter, Subfamily G, Member 8/genetics , Hypercholesterolemia/genetics , Hypercholesterolemia/drug therapy , Hypercholesterolemia/diagnosis , Ezetimibe/therapeutic use , Xanthomatosis/genetics , Xanthomatosis/pathology , Xanthomatosis/diagnosis , Anticholesteremic Agents/therapeutic use , Anticholesteremic Agents/administration & dosage , Mutation , ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics , Homozygote , Child , Heterozygote , Lipoproteins/genetics
9.
Food Chem ; 439: 138173, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38100868

ABSTRACT

This study aimed to evaluate the effect of temperature (20, 25, and 30 °C) and relative humidity (RH, 50, 55, and 60 %) as abiotic stressors during oat (Avena sativa L.) germination using a 2-level factorial design with central point. UPLC-QToF-MSE identified eighty polyphenols, nine avenanthramides, twelve lignans, and five phytosterols Notably, 100 % germination was achieved at 25 °C/60 % RH from day 3, yielding the longest radicle size. The highest content of most phenolic acids, avenanthramides, and lignans occurred at 30 °C/65 % RH, where 100 % germination was attained by day 5, but with a shorter radicle size. The best flavonoid and phytosterol profle was obtained at 20 °C/55 % RH, achieving only a 67 % germination rate. Therefore, while these conditions enhance the bioactive compound profile, the associate decrease in germination metrics suggests potential distress effects. Consideration of both photochemical outcomes and germination yield is crucial for comprehensive assessments in future applications.


Subject(s)
Lignans , Phytosterols , Avena/chemistry , Temperature , Humidity , Phytochemicals/chemistry , Germination
10.
Steroids ; 200: 109323, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37813157

ABSTRACT

Herein we report an unprecedented and efficient methodology for accessing 6-alkoxy-Δ4,6-diene-3-one derivatives. Such scaffolds were serendipitously obtained in the course of the study of the reaction of Δ4-3-keto steroids with catalytic amounts of iodine in refluxing methanol. A series of 6-methoxy and 6-ethoxy- Δ4,6-diene-3-ones were prepared from easily-available sterols in a two-step sequence; first, oxidation of sterols furnished the Δ4-3-keto steroids, which were then refluxed with ethanol or methanol with I2 as catalyst to obtain a series of ten derivatives. Furthermore, this protocol was also effective for the introduction of a larger carbon chain at C-6. Druglikeliness properties of synthesized compounds were predicted using the SwissADME tool.


Subject(s)
Phytosterols , Sterols , Methanol , Steroids
11.
PLoS Biol ; 21(8): e3002257, 2023 08.
Article in English | MEDLINE | ID: mdl-37619212

ABSTRACT

Cholesterol contributes to neuronal membrane integrity, supports membrane protein clustering and function, and facilitates proper signal transduction. Extensive evidence has shown that cholesterol imbalances in the central nervous system occur in aging and in the development of neurodegenerative diseases. In this work, we characterize cholesterol homeostasis in the inner ear of young and aged mice as a new unexplored possibility for the prevention and treatment of hearing loss. Our results show that cholesterol levels in the inner ear are reduced during aging, an effect that is associated with an increased expression of the cholesterol 24-hydroxylase (CYP46A1), the main enzyme responsible for cholesterol turnover in the brain. In addition, we show that pharmacological activation of CYP46A1 with the antiretroviral drug efavirenz reduces the cholesterol content in outer hair cells (OHCs), leading to a decrease in prestin immunolabeling and resulting in an increase in the distortion product otoacoustic emissions (DPOAEs) thresholds. Moreover, dietary supplementation with phytosterols, plant sterols with structure and function similar to cholesterol, was able to rescue the effect of efavirenz administration on the auditory function. Altogether, our findings point towards the importance of cholesterol homeostasis in the inner ear as an innovative therapeutic strategy in preventing and/or delaying hearing loss.


Subject(s)
HIV Infections , Hearing Loss , Phytosterols , Animals , Mice , Cholesterol 24-Hydroxylase , Hearing Loss/chemically induced
12.
Methods Mol Biol ; 2704: 43-50, 2023.
Article in English | MEDLINE | ID: mdl-37642837

ABSTRACT

The phytosterol-biotransforming strains can be selected from Mycobacterium sp. using a high concentration of ß-sitosterol. The selection is made by culturing the strains in a medium enriched with 14 g/L of ß-sitosterol as the unique source of carbon. During 2 months, the bacterial cultures are transferred successively. The extraction of the biotransformation products is made with methanol and ethyl acetate. The qualitative and quantitative analyses are made by means of thin-layer chromatography, gas-liquid chromatography (GLC), and GLC-mass spectrometry. Under these conditions, it is observed that after seven transfers, the strains Mycobacterium sp. MB-3683 and Mycobacterium fortuitum B-11045 increase their biotransformation capacity from 20% to 64% and from 34% to 55%, respectively. The products in the highest proportion identified for each trial are androstenedione and androstadienedione. The results suggest that the high substrate concentration could be a selective mechanism to obtain strains more efficient in the biotransformation of ß-sitosterol into steroidal bases.


Subject(s)
Phytosterols , Gas Chromatography-Mass Spectrometry , Androstenedione , Carbon , Chromatography, Thin Layer
13.
Methods Mol Biol ; 2704: 329-336, 2023.
Article in English | MEDLINE | ID: mdl-37642854

ABSTRACT

Stigmasterol is a phytosterol contained in kraft mill effluent that is able to increase over 100% after aerobic biological treatment. This compound can act as an endocrine disrupter as its structure is similar to that of cholesterol. Furthermore, stigmasterol contained in kraft mill effluent shows high toxicity (25-fold more than ß-sitosterol) to aquatic organisms such as Daphnia magna. However, the operation of the aerobic treatment and biomass adaptation could be affecting their removal. The performances of activated sludge (AS), aerated lagoon (AL), and moving bed biofilm reactors (MBBR) are compared to remove the stigmasterol contained in kraft mill effluent. The AL operates at a hydraulic retention time of 6 h and removes up to 90% of phytosterols. So, a 96% of stigmasterol is removed by AL when the sterol retention load is 0.6 mg/L · d. However, stigmasterol concentrations increase from 29% to 37% at a low stigmasterol load rate (0.2 mg/L · d). On the other hand, the stigmasterol is removed between 65% and 87% by an AS under a hydraulic retention time of 3 h. Moreover, a 100% of stigmasterol can be removed by the MBBR when the hydraulic retention time is 2 days.


Subject(s)
Phytosterols , Stigmasterol , Biofilms , Bioreactors , Acclimatization , Sewage
14.
Adv Food Nutr Res ; 105: 97-172, 2023.
Article in English | MEDLINE | ID: mdl-37516469

ABSTRACT

Lipids represent one out of three major macronutrient classes in the human diet. It is estimated to account for about 15-20% of the total dietary intake. Triacylglycerides comprise the majority of them, estimated 90-95%. Other lipid classes include free fatty acids, phospholipids, cholesterol, and plant sterols as minor components. Various methods are used for the characterization of nutritional lipids, however, lipidomics approaches become increasingly attractive for this purpose due to their wide coverage, comprehensiveness and holistic view on composition. In this chapter, analytical methodologies and workflows utilized for lipidomics profiling of food samples are outlined with focus on mass spectrometry-based assays. The chapter describes common lipid extraction protocols, the distinct instrumental mass-spectrometry based analytical platforms for data acquisition, chromatographic and ion-mobility spectrometry methods for lipid separation, briefly mentions alternative methods such as gas chromatography for fatty acid profiling and mass spectrometry imaging. Critical issues of important steps of lipidomics workflows such as structural annotation and identification, quantification and quality assurance are discussed as well. Applications reported over the period of the last 5years are summarized covering the discovery of new lipids in foodstuff, differential profiling approaches for comparing samples from different origin, species, varieties, cultivars and breeds, and for food processing quality control. Lipidomics as a powerful tool for personalized nutrition and nutritional intervention studies is briefly discussed as well. It is expected that this field is significantly growing in the near future and this chapter gives a short insight into the power of nutritional lipidomics approaches.


Subject(s)
Lipids , Phytosterols , Humans , Lipids/chemistry , Lipidomics/methods , Mass Spectrometry/methods , Fatty Acids
15.
Chem Biodivers ; 20(7): e202300536, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37335297

ABSTRACT

In this study, twelve campesterol derivatives (2-13) were prepared by esterification reaction at the hydroxy group in C-3 and catalytic hydrogenation at the carbon-carbon double bond in C-5(6). All obtained compounds were characterized by IR, 1 H-NMR, 13 C-NMR, and MS spectra. Campesterol (1) and its derivatives (2-13) were evaluated in vitro against Staphylococcus aureus (ATCC 6538), Streptococcus mutans (ATCC 0046), Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 15442), and Klebsiella pneumoniae (ATCC 10031) using the microdilution method. Among tested compounds, 4, 6, 9, 11, 12, and 13 displayed the best antibacterial activity. Moreover, to support the antibacterial activity experiments, the investigation of molecular interactions of more active compounds, and also compound 1 and neomycin, used as starting material and positive control, respectively, at the binding site of the target proteins was performed using molecular docking simulations. Four compounds (7, 9, 10 and 11) are herein described for the first time.


Subject(s)
Anti-Bacterial Agents , Phytosterols , Molecular Docking Simulation , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry
16.
Curr Atheroscler Rep ; 25(5): 181-187, 2023 05.
Article in English | MEDLINE | ID: mdl-36897412

ABSTRACT

PURPOSE OF REVIEW: The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels of plasma plant sterols. This sterol storage condition is caused by biallelic loss-of-function genetic variants in either ABCG5 or ABCG8, leading to increased intestinal absorption and decreased hepatic excretion of plant sterols. Clinically, patients with sitosterolemia usually exhibit xanthomatosis, high levels of plasma cholesterol, and premature atherosclerotic disease, but presentation can be highly heterogeneous. Therefore, recognition of this condition requires a high level of suspicion, with confirmation upon genetic diagnosis or through measurement of plasma phytosterols. Treatment of sitosterolemia with both a plant sterol-restricted diet and the intestinal cholesterol absorption inhibitor ezetimibe can reduce efficiently the levels of plasma plant sterols, consisting in the first-line therapy for this disease. RECENT FINDINGS: Since hypercholesterolemia is often present in individuals with sitosterolemia, it is important to search for genetic variants in ABCG5 and ABCG8 in patients with clinical criteria for familial hypercholesterolemia (FH), but no variants in FH implicated genes. Indeed, recent studies have suggested that genetic variants in ABCG5/ABCG8 can mimic FH, and even when in heterozygosis, they may potentially exacerbate the phenotype of patients with severe dyslipidemia. Sitosterolemia is a genetic lipid disorder characterized by increased circulating levels of plant sterols and clinically manifested by xanthomatosis, hematologic disorders, and early atherosclerosis. Awareness about this condition, a rare, but commonly underdiagnosed and yet treatable cause of premature atherosclerotic disease, is imperative.


Subject(s)
Atherosclerosis , Hypercholesterolemia , Hyperlipoproteinemia Type II , Intestinal Diseases , Lipid Metabolism, Inborn Errors , Phytosterols , Xanthomatosis , Humans , Hypercholesterolemia/drug therapy , Phytosterols/adverse effects , Phytosterols/genetics , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/genetics , Lipid Metabolism, Inborn Errors/therapy , Intestinal Diseases/diagnosis , Intestinal Diseases/genetics , Intestinal Diseases/drug therapy , Hyperlipoproteinemia Type II/complications , Cholesterol , Xanthomatosis/etiology , Atherosclerosis/genetics , Atherosclerosis/complications
17.
Int J Mol Sci ; 23(19)2022 Oct 09.
Article in English | MEDLINE | ID: mdl-36233298

ABSTRACT

BACKGROUND: Increased cholesterol absorption and reduced synthesis are processes that have been associated with cardiovascular disease risk in a controversial way. However, most of the studies involving markers of cholesterol synthesis and absorption include conditions, such as obesity, diabetes, dyslipidemia, which can be confounding factors. The present study aimed at investigating the relationships of plasma cholesterol synthesis and absorption markers with cardiovascular disease (CVD) risk factors, cIMT (carotid intima-media thickness), and the presence of carotid plaques in asymptomatic subjects. METHODS: A cross-sectional study was carried out in 270 asymptomatic individuals and anthropometrical parameters, fasting plasma lipids, glucometabolic profiles, high-sensitivity C-reactive protein (hs-CRP), markers of cholesterol synthesis (desmosterol and lathosterol), absorption (campesterol and sitosterol), cIMT, and the presence of atherosclerotic plaques were analyzed. RESULTS: Among the selected subjects aged between 19 and 75 years, 51% were females. Age, body mass index, systolic and diastolic blood pressure, total cholesterol, non-HDL-C, triglycerides, glucose, and lathosterol/sitosterol ratios correlated positively with cIMT (p ≤ 0.05). Atherosclerotic plaques were present in 19% of the subjects. A direct association of carotid plaques with campesterol, OR = 1.71 (95% CI = 1.04-2.82, p ≤ 0.05) and inverse associations with both ratios lathosterol/campesterol, OR = 0.29 (CI = 0.11-0.80, p ≤ 0.05) and lathosterol/sitosterol, OR = 0.45 (CI = 0.22-0.95, p ≤ 0.05) were observed in univariate logistic regression analysis. CONCLUSIONS: The findings suggested that campesterol may be associated with atherosclerotic plaques and the lathosterol/campesterol or sitosterol ratios suggested an inverse association. Furthermore, synthesis and absorption of cholesterol are inverse processes, and the absorption marker, campesterol, may reflect changes in body cholesterol homeostasis with atherogenic potential.


Subject(s)
Cardiovascular Diseases , Phytosterols , Plaque, Atherosclerotic , Adult , Aged , Biomarkers/metabolism , C-Reactive Protein , Carotid Intima-Media Thickness , Cholesterol/analogs & derivatives , Cholesterol/metabolism , Cross-Sectional Studies , Desmosterol , Female , Glucose , Humans , Male , Middle Aged , Sitosterols , Triglycerides , Young Adult
18.
Molecules ; 27(10)2022 May 15.
Article in English | MEDLINE | ID: mdl-35630641

ABSTRACT

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.


Subject(s)
Androstenedione , Phytosterols , Androgens , Androstenedione/metabolism , Biotransformation , Mycobacteriaceae , Phytosterols/chemistry , Steroids/metabolism
19.
Methods Mol Biol ; 2469: 119-128, 2022.
Article in English | MEDLINE | ID: mdl-35508834

ABSTRACT

Triterpene saponins of the genus Quillaja (Quillajaceae) are known for their immunoadjuvant, hypocholesterolemic, and anti-inflammatory activity. Plant cell cultures are useful for the study of saponin metabolism and industrial production of these bioactive compounds. While structurally related phytosterols are primary metabolites essential to growth and development, saponins are responsive to pathogen and abiotic stress, fulfilling roles in plant specialized metabolism. For cell culture production of saponins, phytosterols may be considered a competing pathway which relies on a common pool of cytosolic isoprenoid precursors.Understanding the metabolic allocation of resources between these two related pathways is key to maximizing saponin production in in vitro production systems. Sterols and saponins naturally occur in multiple conjugated forms, which complicate separation and quantification. The acid hydrolysis of conjugated sterols and saponins to their free forms is a useful technique to simplify their analysis by gas chromatography. Here we provide the workflow for the quantification of free sterols and sapogenins in cell cultures of Quillaja brasiliensis .


Subject(s)
Phytosterols , Sapogenins , Saponins , Triterpenes , Cell Culture Techniques , Gas Chromatography-Mass Spectrometry , Quillaja/chemistry , Saponins/chemistry , Sterols
20.
Clinics (Sao Paulo) ; 77: 100028, 2022.
Article in English | MEDLINE | ID: mdl-35397367

ABSTRACT

OBJECTIVES: Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol, the authors investigated whether the plasma Phytosterols (PS) relate to the body's cholesterol synthesis rate measured as non-cholesterol sterol precursors (lathosterol). METHOD: The authors studied 38 non-obese volunteers (58±12 years; Low-Density Lipoprotein Cholesterol ‒ LDL-C ≥ 130 mg/dL) randomly assigned to consume 400 mL/day of soy milk (Control phase) or soy milk + PS (1.6 g/day) for four weeks in a double-blind, cross-over study. PS and lathosterol were measured in plasma by gas chromatography coupled to mass spectrophotometry. RESULTS: PS treatment reduced plasma total cholesterol concentration (-5.5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration), but plasma lathosterol, campesterol and sitosterol expressed per plasma cholesterol increased. CONCLUSIONS: The lathosterol-to-cholesterol plasma ratio predicted the plasma cholesterol response to PS feeding. The highest plasma lathosterol concentration during the control phase was associated with a lack of response of plasma cholesterol during the PS treatment period. Consequently, cholesterol synthesis in non-responders to dietary PS being elevated in the control phase indicates these cases resist to further synthesis rise, whereas responders to dietary PS, having in the control phase synthesis values lower than non-responders, expand synthesis on alimentary PS. Responders absorb more PS than non-responders, likely resulting from responders delivering into the intestinal lumen less endogenous cholesterol than non-responders do, thus facilitating greater intestinal absorption of PS shown as increased plasma PS concentration.


Subject(s)
Cholesterol , Phytosterols , Cholesterol, HDL , Cholesterol, LDL , Cross-Over Studies , Humans
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