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Fulltext The Efficacy of Squalene in Cardiovascular Disease Risk-A Systematic Review

Ibrahim N', Fairus S, Zulfarina MS, Naina Mohamed I

Nutrients, 2020 Feb 05;12(2).
PMID: 32033387 DOI: 10.3390/nu12020414

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death worldwide. Squalene (SQ), an intermediate for the cholesterol biosynthesis, has been proposed to act similarly to statins via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the liver.
PURPOSE: This paper explores the effects of SQ in CVD.
METHODS: A systematic review of the literature was performed to identify relevant studies about SQ and CVD. A comprehensive search in Medline and Scopus for relevant studies published between the years 1946 and 2019 was performed. The main inclusion criteria were that the study was published in English; that the study reported association or effect of SQ and CVD; and that CVD should be related to lifestyle variables, aging, or experimentally induced conditions.
RESULTS: The literature searches identified 5562 potentially relevant articles, whereby 21 studies met the inclusion criteria. There were three human studies and 18 animal experimental studies included in this paper. Only one human study reported positive outcome of SQ in CVD. The remaining two studies reported inconsistent and/or no effect. For animal studies, 15 studies reported positive effect while the remaining reported negative and/or no effect of SQ on various related parameters.
CONCLUSIONS: This evidence-based review emphasizes the potential of SQ being used for cardiovascular-related diseases. The effect of SQ, especially of plant-based warrants further exploration. Controlled human observational studies should be performed to provide comprehensive evidence.

Matched MeSH terms: Hydroxymethylglutaryl CoA Reductases/drug effects*
Antioxidative and Inhibitory Effects of the Fruiting Body of Black Lingzhi Mushroom, Amauroderma rugosum (Agaricomycetes), on LDL Oxidation and HMG-CoA Reductase Activity

Seng CK, Abdullah N, Aminudin N

Int J Med Mushrooms, 2017;19(9):797-807.
PMID: 29199554 DOI: 10.1615/IntJMedMushrooms.2017024374

Amauroderma rugosum fruiting bodies possess excellent cardiovascular benefits, including antioxidative, antihyperlipidemic, antihypertensive, antiinflammatory, anti-platelet aggregation, and antithrombotic effects. In this article, we describe our investigations of the in vitro antioxidant activity and in vitro antiatherosclerotic potential through inhibitory effects on low-density lipoprotein (LDL), LDL peroxidation, and 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalytic activity using various fruiting body extracts partitioned with an organic solvent. Among 5 extracts/fractions tested, the semipolar ethyl acetate (EA) fraction demonstrated good antioxidant capacity based on total phenolic content, 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, ferrous ion-chelating ability, cupric ion-reducing antioxidant capacity, and lipid peroxidation assays. The EA fraction also showed the strongest inhibitory effect on Cu2+-induced LDL oxidation via thiobarbituric acid reactive substances formation and HMG-CoA reductase activity. Chemical analysis conjointly identified 10 phenolic compounds (4 benzoic acid derivatives, 3 flavonoids, 1 cinnamic acid, 1 hexahydroxydiphenic acid dilactone, and 1 xanthone derivative), some of which play pivotal roles in arresting the physiopathogenesis of atherosclerosis, thereby attenuating the risk of cardiovascular events occurring.

Matched MeSH terms: Hydroxymethylglutaryl CoA Reductases/drug effects
Regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase gene expression by thymoquinone-rich fraction and thymoquinone in HepG2 cells

Al-Naqeep G, Ismail M, Allaudin Z

J Nutrigenet Nutrigenomics, 2009;2(4-5):163-72.
PMID: 19887822 DOI: 10.1159/000227264

BACKGROUND AND AIM: Nigella sativa and its active constituent thymoquinone (TQ) have been exploited for their various health benefits. This work was aimed to investigate the regulatory effects of TQ-rich fraction (TQRF) and commercial TQ on the low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) genes in HepG2 cells.
METHODS AND RESULTS: TQRF was extracted from N. sativa seeds using supercritical fluid extraction. The regulatory effects of TQRF at 80 microg/ml and TQ at 2 microg/ml on LDLR and HMGCR gene expression were investigated in HepG2 cells using quantitative real-time PCR. The TQ content in TQRF was 2.77% (w/w) and was obtained at a temperature of 40 degrees C and a pressure of 600 bar. Treatment of cells with TQRF and TQ resulted in a 7- and 2-fold upregulation of LDLR mRNA level, respectively, compared with untreated cells. The mRNA level of HMGCR was downregulated by 71 and 12%, respectively, compared with untreated cells.
CONCLUSION: TQRF and TQ regulated genes involved in cholesterol metabolism by two mechanisms, the uptake of low-density lipoprotein cholesterol via the upregulation of the LDLR gene and inhibition of cholesterol synthesis via the suppression of the HMGCR gene.

Matched MeSH terms: Hydroxymethylglutaryl CoA Reductases/drug effects
Fulltext Inhibitory effect on in vitro LDL oxidation and HMG Co-A reductase activity of the liquid-liquid partitioned fractions of Hericium erinaceus (Bull.) Persoon (lion's mane mushroom)

Rahman MA, Abdullah N, Aminudin N

Biomed Res Int, 2014;2014:828149.
PMID: 24959591 DOI: 10.1155/2014/828149

Oxidation of low-density lipoprotein (LDL) has been strongly suggested as the key factor in the pathogenesis of atherosclerosis. Mushrooms have been implicated in having preventive effects against chronic diseases due especially to their antioxidant properties. In this study, in vitro inhibitory effect of Hericium erinaceus on LDL oxidation and the activity of the cholesterol biosynthetic key enzyme, 3-hydroxy-3-methyl glutaryl coenzyme A (HMG Co-A) reductase, was evaluated using five liquid-liquid solvent fractions consisting of methanol : dichloromethane (M : DCM), hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), and aqueous residue (AQ). The hexane fraction showed the highest inhibition of oxidation of human LDL as reflected by the increased lag time (100 mins) for the formation of conjugated diene (CD) at 1 µg/mL and decreased production (68.28%, IC50 0.73 mg/mL) of thiobarbituric acid reactive substances (TBARS) at 1 mg/mL. It also mostly inhibited (59.91%) the activity of the HMG Co-A reductase at 10 mg/mL. The GC-MS profiling of the hexane fraction identified the presence of myconutrients: inter alia, ergosterol and linoleic acid. Thus, hexane fraction of Hericium erinaceus was found to be the most potent in vitro inhibitor of both LDL oxidation and HMG Co-A reductase activity having therapeutic potential for the prevention of oxidative stress-mediated vascular diseases.

Matched MeSH terms: Hydroxymethylglutaryl CoA Reductases/drug effects*