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Molecular Effects of Phytochemicals on Cholesterol Metabolism Genes

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 17638

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Special Issue Editor

Prof. Dr. Jui-Hung Yen

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Guest Editor

Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 97004, Taiwan
Interests: phytochemicals; food chemistry; lipid metabolism; leukemia; neuroprotection
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Dysregulation of cholesterol metabolism is not only associated with atherosclerotic cardiovascular diseases but also other diseases, such as cancers and neurodegenerative disorders. Modulation of plasma cholesterol levels may be achieved by diet and lifestyle changes or the use of pharmacological interventions for the regulation of cholesterol metabolism genes such as HMGCR inhibitors (statins), PCSK9 or Mylip/Idol inhibitors (LDLR degradation inhibitors), and NPC1L1 inhibitors (cholesterol absorption inhibitors) can significantly improve the clinical outcome of these events. In recent years, phytochemicals such as polyphenols, flavonoids, isoflavonoids, and terpenoids have been reported to possess a broad spectrum of pharmacological and biological activities and are considered promising agents for the maintenance of cholesterol homeostasis. Therefore, I will highlight the molecular effects of phytochemicals in the regulation of genes and signaling pathways involved in the cholesterol metabolism. In this Special Issue, we invite paper submissions regarding the molecular effects and underlying mechanisms of phytochemicals on the modulation of cholesterol metabolism genes for the management of lipid dysregulation in the prevention or treatment of chronic diseases.

Prof. Dr. Jui-Hung Yen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

atherosclerotic cardiovascular diseases
cancers
neurodegenerative disorders
cholesterol metabolism genes
phytochemicals
polyphenols
flavonoids

Published Papers (5 papers)

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Research

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12 pages, 1068 KiB

Open AccessArticle

The Association between Single Nucleotide Polymorphisms, including miR-499a Genetic Variants, and Dyslipidemia in Subjects Treated with Pharmacological or Phytochemical Lipid-Lowering Agents

by Angelica Giuliani, Alberto Montesanto, Giulia Matacchione, Laura Graciotti, Deborah Ramini, Olga Protic, Roberta Galeazzi, Roberto Antonicelli, Elena Tortato, Anna Rita Bonfigli, Jacopo Sabbatinelli and Fabiola Olivieri

Int. J. Mol. Sci. 2022, 23(10), 5617; https://doi.org/10.3390/ijms23105617 - 17 May 2022

Cited by 2 | Viewed by 1755

Abstract

Disorders of lipoprotein metabolism are among the major risk factors for cardiovascular disease (CVD) development. Single nucleotide polymorphisms (SNPs) have been associated with the individual variability in blood lipid profile and response to lipid-lowering treatments. Here, we genotyped 34 selected SNPs located in coding genes related to lipid metabolism, inflammation, coagulation, and a polymorphism in the MIR499 gene—a microRNA previously linked to CVD—to evaluate the association with lipid trait in subjects with moderate dyslipidemia not on lipid-lowering treatment (Treatment-naïve (TN) cohort, n = 125) and in patients treated with statins (STAT cohort, n = 302). We also explored the association between SNPs and the effect of a novel phytochemical lipid-lowering treatment in the TN cohort. We found that 6 SNPs (in the MIR499, TNFA, CETP, SOD2, and VEGFA genes) were associated with lipid traits in the TN cohort, while no association was found with the response to twelve-week phytochemical treatment. In the STAT cohort, nine SNPs (in the MIR499, CETP, CYP2C9, IL6, ABCC2, PON1, IL10, and VEGFA genes) were associated with lipid traits, three of which were in common with the TN cohort. Interestingly, in both cohorts, the presence of the rs3746444 MIR499 SNP was associated with a more favorable blood lipid profile. Our findings could add information to better understand the individual genetic variability in maintaining a low atherogenic lipid profile and the response to different lipid-lowering therapies. Full article

(This article belongs to the Special Issue Molecular Effects of Phytochemicals on Cholesterol Metabolism Genes)

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Review

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30 pages, 2040 KiB

Open AccessReview

Regulation of Cholesterol Metabolism by Phytochemicals Derived from Algae and Edible Mushrooms in Non-Alcoholic Fatty Liver Disease

by Yahav Eilam, Noam Pintel, Hamdan Khattib, Natalie Shagug, Raged Taha and Dorit Avni

Int. J. Mol. Sci. 2022, 23(22), 13667; https://doi.org/10.3390/ijms232213667 - 08 Nov 2022

Cited by 7 | Viewed by 6468

Abstract

Cholesterol synthesis occurs in almost all cells, but mainly in hepatocytes in the liver. Cholesterol is garnering increasing attention for its central role in various metabolic diseases. In addition, cholesterol is one of the most essential elements for cells as both a structural source and a player participating in various metabolic pathways. Accurate regulation of cholesterol is necessary for the proper metabolism of fats in the body. Disturbances in cholesterol homeostasis have been linked to various metabolic diseases, such as hyperlipidemia and non-alcoholic fatty liver disease (NAFLD). For many years, the use of synthetic chemical drugs has been effective against many health conditions. Furthermore, from ancient to modern times, various plant-based drugs have been considered local medicines, playing important roles in human health. Phytochemicals are bioactive natural compounds that are derived from medicinal plants, fruit, vegetables, roots, leaves, and flowers and are used to treat a variety of diseases. They include flavonoids, carotenoids, polyphenols, polysaccharides, vitamins, and more. Many of these compounds have been proven to have antioxidant, anti-inflammatory, antiobesity and antihypercholesteremic activity. The multifaceted role of phytochemicals may provide health benefits to humans with regard to the treatment and control of cholesterol metabolism and the diseases associated with this disorder, such as NAFLD. In recent years, global environmental climate change, the COVID-19 pandemic, the current war in Europe, and other conflicts have threatened food security and human nutrition worldwide. This further emphasizes the urgent need for sustainable sources of functional phytochemicals to be included in the food industry and dietary habits. This review summarizes the latest findings on selected phytochemicals from sustainable sources—algae and edible mushrooms—that affect the synthesis and metabolism of cholesterol and improve or prevent NAFLD. Full article

(This article belongs to the Special Issue Molecular Effects of Phytochemicals on Cholesterol Metabolism Genes)

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24 pages, 1652 KiB

Open AccessReview

The Role of Polyphenol in Modulating Associated Genes in Diabetes-Induced Vascular Disorders

by Nor Anizah Mohd Nor, Siti Balkis Budin, Satirah Zainalabidin, Juriyati Jalil, Syaifuzah Sapian, Fatin Farhana Jubaidi and Nur Najmi Mohamad Anuar

Int. J. Mol. Sci. 2022, 23(12), 6396; https://doi.org/10.3390/ijms23126396 - 07 Jun 2022

Cited by 14 | Viewed by 2695

Abstract

Diabetes-induced vascular disorder is considered one of the deadly risk factors among diabetic patients that are caused by persistent hyperglycemia that eventually leads to cardiovascular diseases. Elevated reactive oxygen species (ROS) due to high blood glucose levels activate signaling pathways such as AGE/RAGE, PKC, polyol, and hexosamine pathways. The activated signaling pathway triggers oxidative stress, inflammation, and apoptosis which later lead to vascular dysfunction induced by diabetes. Polyphenol is a bioactive compound that can be found abundantly in plants such as vegetables, fruits, whole grains, and nuts. This compound exerts therapeutic effects in alleviating diabetes-induced vascular disorder, mainly due to its potential as an anti-oxidative, anti-inflammatory, and anti-apoptotic agent. In this review, we sought to summarize the recent discovery of polyphenol treatments in modulating associated genes involved in the progression of diabetes-induced vascular disorder. Full article

(This article belongs to the Special Issue Molecular Effects of Phytochemicals on Cholesterol Metabolism Genes)

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23 pages, 8795 KiB

Open AccessReview

Antiretroviral Therapy-Induced Dysregulation of Gene Expression and Lipid Metabolism in HIV+ Patients: Beneficial Role of Antioxidant Phytochemicals

by Angélica Saraí Jiménez-Osorio, Sinaí Jaen-Vega, Eduardo Fernández-Martínez, María Araceli Ortíz-Rodríguez, María Fernanda Martínez-Salazar, Reyna Cristina Jiménez-Sánchez, Olga Rocío Flores-Chávez, Esther Ramírez-Moreno, José Arias-Rico, Felipe Arteaga-García and Diego Estrada-Luna

Int. J. Mol. Sci. 2022, 23(10), 5592; https://doi.org/10.3390/ijms23105592 - 17 May 2022

Cited by 1 | Viewed by 2526

Abstract

Human immunodeficiency virus (HIV) infection has continued to be the subject of study since its discovery nearly 40 years ago. Significant advances in research and intake of antiretroviral therapy (ART) have slowed the progression and appearance of the disease symptoms and the incidence of concomitant diseases, which are the leading cause of death in HIV+ persons. However, the prolongation of ART is closely related to chronic degenerative diseases and pathologies caused by oxidative stress (OS) and alterations in lipid metabolism (increased cholesterol levels), both of which are conditions of ART. Therefore, recent research focuses on using natural therapies to diminish the effects of ART and HIV infection: regulating lipid metabolism and reducing OS status. The present review summarizes current information on OS and cholesterol metabolism in HIV+ persons and how the consumption of certain phytochemicals can modulate these. For this purpose, MEDLINE and SCOPUS databases were consulted to identify publications investigating HIV disease and natural therapies and their associated effects. Full article

(This article belongs to the Special Issue Molecular Effects of Phytochemicals on Cholesterol Metabolism Genes)

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18 pages, 1496 KiB

Open AccessReview

Viral Hepatitis, Cholesterol Metabolism, and Cholesterol-Lowering Natural Compounds

by Je-Wen Liou, Hemalatha Mani and Jui-Hung Yen

Int. J. Mol. Sci. 2022, 23(7), 3897; https://doi.org/10.3390/ijms23073897 - 31 Mar 2022

Cited by 16 | Viewed by 3562

Abstract

Hepatitis is defined as inflammation of the liver; it can be acute or chronic. In chronic cases, the prolonged inflammation gradually damages the liver, resulting in liver fibrosis, cirrhosis, and sometimes liver failure or cancer. Hepatitis is often caused by viral infections. The most common causes of viral hepatitis are the five hepatitis viruses—hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). While HAV and HEV rarely (or do not) cause chronic hepatitis, a considerable proportion of acute hepatitis cases caused by HBV (sometimes co-infected with HDV) and HCV infections become chronic. Thus, many medical researchers have focused on the treatment of HBV and HCV. It has been documented that host lipid metabolism, particularly cholesterol metabolism, is required for the hepatitis viral infection and life cycle. Thus, manipulating host cholesterol metabolism-related genes and proteins is a strategy used in fighting the viral infections. Efforts have been made to evaluate the efficacy of cholesterol-lowering drugs, particularly 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, in the treatment of hepatitis viral infections; promising results have been obtained. This review provides information on the relationships between hepatitis viruses and host cholesterol metabolism/homeostasis, as well as the discovery/development of cholesterol-lowering natural phytochemicals that could potentially be applied in the treatment of viral hepatitis. Full article

(This article belongs to the Special Issue Molecular Effects of Phytochemicals on Cholesterol Metabolism Genes)

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