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Current Pharmaceutical Design 2021Plant-derived sterols, phytosterols, are well known for their cholesterol-lowering activity in serum and their anti-inflammatory activities. Recently, phytosterols have... (Review)
Review
Plant-derived sterols, phytosterols, are well known for their cholesterol-lowering activity in serum and their anti-inflammatory activities. Recently, phytosterols have received considerable attention due to their beneficial effects on various non-communicable diseases, and recommended use as daily dietary components. The signaling pathways mediated in the brain by phytosterols have been evaluated, but little is known about their effects on neuroinflammation, and no clinical studies have been undertaken on phytosterols of interest. In this review, we discuss the beneficial roles of phytosterols, including their attenuating effects on inflammation, blood cholesterol levels, and hallmarks of the disease, and their regulatory effects on neuroinflammatory disease pathways. Despite recent advancements made in phytosterol pharmacology, some critical questions remain unanswered. Therefore, we have tried to highlight the potential of phytosterols as viable therapeutics against neuroinflammation and to direct future research with respect to clinical applications.
Topics: Anti-Inflammatory Agents; Cholesterol; Diet; Humans; Phytosterols
PubMed: 32600224
DOI: 10.2174/1381612826666200628022812 -
Current Atherosclerosis Reports May 2023The purpose of this review was to summarize important and updated information on sitosterolemia. Sitosterolemia is an inherited lipid disorder consisting of high levels... (Review)
Review
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.
Topics: Humans; Hypercholesterolemia; Phytosterols; Lipid Metabolism, Inborn Errors; Intestinal Diseases; Hyperlipoproteinemia Type II; Cholesterol; Xanthomatosis; Atherosclerosis
PubMed: 36897412
DOI: 10.1007/s11883-023-01092-4 -
Lipids in Health and Disease Jan 2022Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The... (Review)
Review
BACKGROUND
Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The disease is frequently misdiagnosed and mistreated as familial hypercholesterolemia (FH). To gain a better understanding of the disease, the current status of diagnosis and treatment of Chinese patients with sitosterolemia was reviewed and summarized.
METHOD
Literature search was performed. The clinical features and molecular characteristics of Chinese patients with sitosterolemia were analysed. Four children with sitosterolemia and the treatment experience were described.
RESULTS
Fifty-five patients with sitosterolemia have been reported in China. These patients were aged from 3 months to 67 years at diagnosis, and the median was 8 years of age. Several complications, such as xanthomas in 47 patients (85%), thrombocytopenia in 17 patients (31%), anemia in 14 patients (25%), and cardiovascular damage in 12 patients (22%), were observed. Thirty-nine patients (71%) exhibited mutations in the ABCG5 gene, 15 patients (27%) showed mutations in ABCG8, and variations in both genes occurred in one patient (2%). A patient with two clinically rare diseases, namely, sitosterolemia and glycogen storage disease type VI (GSD VI)), is reported here for the first time. The four reported patients were treated with low cholesterol and phytosterol-limited diet alone or combined with cholestyramine. Even though decreases were observed for total plasma cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C), and these levels were as low as normal in some patients, the levels of plant sterols remained above the normal range. However, TC, LDL-C and plant sterol levels remained at high levels in patients treated with a control diet control only.
CONCLUSIONS
The analysis reveals that different from Caucasians carrying mainly variations in ABCG8, most Chinese patients have mutations in the ABCG5 gene, and Arg446Ter, Gln251Ter, anArg389His might be hot-spot mutations in Chinese patients. The current survey provides clinical data to enable the development of a standardized protocol for the diagnosis and treatment of sitosterolemia in China.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Adolescent; Adult; Aged; Child; Child, Preschool; China; Female; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Mutation; Phytosterols; Young Adult
PubMed: 35042526
DOI: 10.1186/s12944-021-01619-1 -
Metabolism: Clinical and Experimental Sep 2023Short-term clinical trials have shown the cholesterol-lowering potentials of phytosterols, but their impacts on cardiovascular disease (CVD) remain controversial. This...
BACKGROUND
Short-term clinical trials have shown the cholesterol-lowering potentials of phytosterols, but their impacts on cardiovascular disease (CVD) remain controversial. This study used the Mendelian randomization (MR) to investigate the relationships between genetic predisposition to blood sitosterol concentration and 11 CVD endpoints, along with the potential mediating effects of blood lipids and hematological traits.
METHODS
Random-effect inverse-variance weighted method was used as the main analysis of MR. Genetic instruments of sitosterol (seven SNPs, F = 253, and R = 15.4 %) were derived from an Icelandic cohort. Summary-level data of the 11 CVDs were obtained from UK Biobank, FinnGen, and publicly available genome-wide association study results.
RESULTS
Genetically predicted one unit increment in log-transformed blood total sitosterol was significantly associated with a higher risk of coronary atherosclerosis (OR: 1.52; 95 % CI: 1.41, 1.65; n = 667,551), myocardial infarction (OR: 1.40; 95 % CI: 1.25, 1.56; n = 596,436), all coronary heart disease (OR: 1.33; 95 % CI: 1.22, 1.46; n = 766,053), intracerebral hemorrhage (OR: 1.68; 95 % CI: 1.24, 2.27; n = 659,181), heart failure (OR: 1.16; 95 % CI: 1.08, 1.25; n = 1,195,531), and aortic aneurysm (OR: 1.74; 95 % CI: 1.42, 2.13; n = 665,714). Suggestive associations were observed for an increased risk of ischemic stroke (OR: 1.06; 95 % CI: 1.01, 1.12; n = 2,021,995) and peripheral artery disease (OR: 1.20; 95 % CI: 1.05, 1.37; n = 660,791). Notably, blood non-high-density lipoprotein cholesterol (nonHDL-C) and apolipoprotein B mediated about 38-47 %, 46-60 %, and 43-58 % of the associations between sitosterol and coronary atherosclerosis, myocardial infarction, and coronary heart disease, respectively. However, the associations between sitosterol and CVDs were less likely to depend on hematological traits.
CONCLUSION
The study suggests that genetic predisposition to higher blood total sitosterol is linked to a greater risk of major CVDs. Moreover, blood nonHDL-C and apolipoprotein B might mediate a significant proportion of the associations between sitosterol and coronary diseases.
Topics: Humans; Cardiovascular Diseases; Coronary Artery Disease; Sitosterols; Mendelian Randomization Analysis; Genetic Predisposition to Disease; Phytosterols; Genome-Wide Association Study; Risk Factors; Lipids; Myocardial Infarction; Cholesterol; Apolipoproteins; Polymorphism, Single Nucleotide
PubMed: 37270173
DOI: 10.1016/j.metabol.2023.155611 -
British Journal of Haematology Oct 2019
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; Adult; Genetic Diseases, Inborn; Heterozygote; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Mutation; Phytosterols
PubMed: 31282987
DOI: 10.1111/bjh.16076 -
Molecules (Basel, Switzerland) Dec 2021Fresh and processed food products are rich in bioactive molecules, including polysaccharides, vitamins, carotenoids, peptides, antioxidants, phenolics, phytosterols, and...
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.
Topics: Antioxidants; Carotenoids; Food Handling; Humans; Lipids; Peptides; Phenols; Phytochemicals; Phytosterols; Polysaccharides; Vitamins
PubMed: 34946759
DOI: 10.3390/molecules26247678 -
Journal of Experimental Botany Feb 2021Plants stand out among eukaryotes due to the large variety of sterols and sterol derivatives that they can produce. These metabolites not only serve as critical... (Review)
Review
Plants stand out among eukaryotes due to the large variety of sterols and sterol derivatives that they can produce. These metabolites not only serve as critical determinants of membrane structures, but also act as signaling molecules, as growth-regulating hormones, or as modulators of enzyme activities. Therefore, it is critical to understand the wiring of the biosynthetic pathways by which plants generate these distinct sterols, to allow their manipulation and to dissect their precise physiological roles. Here, we review the complexity and variation of the biosynthetic routes of the most abundant phytosterols and cholesterol in the green lineage and how different enzymes in these pathways are conserved and diverged from humans, yeast, and even bacteria. Many enzymatic steps show a deep evolutionary conservation, while others are executed by completely different enzymes. This has important implications for the use and specificity of available human and yeast sterol biosynthesis inhibitors in plants, and argues for the development of plant-tailored inhibitors of sterol biosynthesis.
Topics: Biosynthetic Pathways; Cholesterol; Phytosterols; Plants; Sterols
PubMed: 32929492
DOI: 10.1093/jxb/eraa429 -
Trends in Plant Science May 2024Plant-microbe interactions (PMIs) are regulated through a wide range of mechanisms in which sterols from plants and microbes are involved in numerous ways, including... (Review)
Review
Plant-microbe interactions (PMIs) are regulated through a wide range of mechanisms in which sterols from plants and microbes are involved in numerous ways, including recognition, transduction, communication, and/or exchanges between partners. Phytosterol equilibrium is regulated by PMIs through expression of genes involved in phytosterol biosynthesis, together with their accumulation. As such, PMI outcomes also include plasma membrane (PM) functionalization events, in which phytosterols have a central role, and activation of sterol-interacting proteins involved in cell signaling. In spite (or perhaps because) of such multifaceted abilities, an overall mechanism of sterol contribution is difficult to determine. However, promising approaches exploring sterol diversity, their contribution to PMI outcomes, and their localization would help us to decipher their crucial role in PMIs.
Topics: Plants; Phytosterols; Sterols; Host-Pathogen Interactions; Host Microbial Interactions; Signal Transduction
PubMed: 38565452
DOI: 10.1016/j.tplants.2024.03.002 -
Current Opinion in Lipidology Aug 2019Familial hypercholesterolemia has long been considered a monogenic disorder. However, recent advances in genetic analyses have revealed various forms of this disorder,... (Review)
Review
PURPOSE OF REVIEW
Familial hypercholesterolemia has long been considered a monogenic disorder. However, recent advances in genetic analyses have revealed various forms of this disorder, including polygenic and oligogenic familial hypercholesterolemia. We review the current understanding of the genetic background of this disease.
RECENT FINDINGS
Mutations in multiple alleles responsible for low-density lipoprotein regulation could contribute to the development of familial hypercholesterolemia, especially among patients with mutation-negative familial hypercholesterolemia. In oligogenic familial hypercholesterolemia, multiple rare genetic variations contributed to more severe familial hypercholesterolemia.
SUMMARY
Familial hypercholesterolemia is a relatively common 'genetic' disorder associated with an extremely high risk of developing coronary artery disease. In addition to monogenic familial hypercholesterolemia, different types of familial hypercholesterolemia, including polygenic and oligogenic familial hypercholesterolemia, exist and have varying degrees of severity. Clinical and genetic assessments for familial hypercholesterolemia and clinical risk stratifications should be performed for accurate diagnosis, as should cascade screening and risk stratification for the offspring of affected patients.
Topics: Animals; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Phytosterols; Risk Assessment
PubMed: 31290811
DOI: 10.1097/QCO.0000000000000563 -
Methods in Molecular Biology (Clifton,... 2023The phytosterol-biotransforming strains can be selected from Mycobacterium sp. using a high concentration of β-sitosterol. The selection is made by culturing the...
The phytosterol-biotransforming strains can be selected from Mycobacterium sp. using a high concentration of β-sitosterol. The selection is made by culturing the strains in a medium enriched with 14 g/L of β-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 β-sitosterol into steroidal bases.
Topics: Phytosterols; Gas Chromatography-Mass Spectrometry; Androstenedione; Carbon; Chromatography, Thin Layer
PubMed: 37642837
DOI: 10.1007/978-1-0716-3385-4_3