Consortia of bioactives in supercritical carbon dioxide extracts of mustard and small cardamom seeds lower serum cholesterol levels in rats: new leads for hypocholesterolaemic supplements from spices

AbstractMelatonin-rich and 1,8-cineole-rich extracts have been successfully obtained from yellow mustard (YM) and small cardamom (SC) seeds, respectively, employing green technology of supercritical CO2 (SC-CO2) extraction. Chemical profiling confirmed the presence of melatonin and 1,8-cineole and co-extractants in the respective extracts. Electron paramagnetic resonance spectroscopy attested strong antioxidant activities of the extracts foregoing pan-assay interference compounds involved in spectroscopic analysis. These extracts also exhibited synergistic efficacies greater than unity confirming antioxidant synergy among the co-extracted bioactives therein. To ascertain hypocholesterolaemic efficacies, these extracts were co-administered orally with Triton X (at the pre-optimised dose of 175 mg/kg body weight (BW)) to Wistar albino rats at doses of 550, 175 and 55 mg/kg BW. Serum total cholesterol levels in the rats were monitored on days 3, 7, 15 and 21. On day 21, total cholesterol level reduced appreciably by 49·44 % in rats treated with YM seed extract and by 48·95 % in rats treated with SC seed extract, comparable with atorvastatin-administered rats (51·09 %). Either extract demonstrated inhibitory effects on hepatic 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase activity. A molecular docking exercise identified specific compounds in the extracts which possessed binding affinities comparable with therapeutically used HMG-CoA reductase inhibitors. In silico and in vivo studies concertedly concluded that the consortium of bioactive components in the extracts cannot be considered as invalid metabolic panaceas and therefore these ‘green’ extracts could be safely subjected to clinical studies as preventive biotherapeutics for hypercholesterolaemia. These extracts could be consumed per se as hypocholesterolaemic supplements or could be ingredients of new spice-based therapeutic foods.

Download Full-text

Bioactive Pigments of Monascus purpureus Attributed to Antioxidant, HMG-CoA Reductase Inhibition and Anti-atherogenic Functions

Frontiers in Sustainable Food Systems ◽

10.3389/fsufs.2021.590427 ◽

2021 ◽

Vol 5 ◽

Author(s):

H. P. Mohankumari ◽

K. Akhilender Naidu ◽

K. Narasimhamurthy ◽

G. Vijayalakshmi

Keyword(s):

Reductase Activity ◽

Lipid Peroxide ◽

Hdl Cholesterol ◽

Monascus Purpureus ◽

Bioactive Metabolites ◽

Hmg Coa Reductase ◽

Cholesterol Levels ◽

Atherogenic Indices ◽

Coa Reductase

Monascus purpureus is known to produce pigment molecules. The pigments were extracted from M. purpureus fermented rice. In-vitro antioxidant effects of pigments were observed and presumed to alleviate oxidative stress related atherosclerosis effect in rats fed with high fat diet (HFD) for 14 weeks. The formation of lipid peroxide due to the oxidation of serum lipid was higher in rats fed with HFD. While, the feeding of fermented rice (groups III-V) significantly lowered the formation of lipid peroxide (27.1–51.7%) in serum of rats, indicated antioxidative effect of pigments. In addition, feeding of fermented rice lowered serum cholesterol and triacylglycerol by 44.82 and 45.30%, respectively. Whereas, LDL-cholesterol levels were decreased by 70.12% and HDL-cholesterol increased by 34.58%. The atherogenic indices (LDL/HDL and TC/HDL) were reduced by 77.80 and 61.05%, respectively, in rats fed with fermented rice. These data confirmed the anti-atherosclerotic effect of pigments. Further liver enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity was significantly inhibited up to 54%. The identification of statins, sterols and fatty acids in fermented rice revealed the HMG-CoA reductase inhibitory activity. This was confirmed by synthesis of lower levels of cholesterol and triacylglycerol in liver of rats fed with fermented rice. Accordingly antioxidant, inhibition of HMG-CoA reductase, anti-atherogenic functions of M. purpureus fermented rice is attributed to the collective effect of bioactive metabolites.

Download Full-text

Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase

Substance Abuse Treatment Prevention and Policy ◽

10.1186/1747-597x-7-12 ◽

2012 ◽

Vol 7 (1) ◽

pp. 12 ◽

Cited By ~ 16

Author(s):

Nina Gårevik ◽

Cristine Skogastierna ◽

Anders Rane ◽

Lena Ekström

Keyword(s):

Single Dose ◽

Total Cholesterol ◽

Hmg Coa Reductase ◽

Cholesterol Levels ◽

Coa Reductase

Download Full-text

The increase in cholesterol levels at early stages after dengue virus infection correlates with an augment in LDL particle uptake and HMG-CoA reductase activity

Virology ◽

10.1016/j.virol.2013.04.003 ◽

2013 ◽

Vol 442 (2) ◽

pp. 132-147 ◽

Cited By ~ 62

Author(s):

Rubén Soto-Acosta ◽

Clemente Mosso ◽

Margot Cervantes-Salazar ◽

Henry Puerta-Guardo ◽

Fernando Medina ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Reductase Activity ◽

Dengue Virus Infection ◽

Hmg Coa Reductase ◽

Particle Uptake ◽

Early Stages ◽

Cholesterol Levels ◽

Coa Reductase

Download Full-text

Inhibitory effects of tangeretin and trans-ethyl caffeate on the HMG-CoA reductase activity: Potential agents for reducing cholesterol levels

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2020.06.010 ◽

2020 ◽

Vol 27 (8) ◽

pp. 1947-1960 ◽

Cited By ~ 1

Author(s):

Inten Pangestika ◽

Efriyana Oksal ◽

Tengku Sifzizul Tengku Muhammad ◽

Hermansyah Amir ◽

Desy Fitrya Syamsumir ◽

...

Keyword(s):

Reductase Activity ◽

Inhibitory Effects ◽

Hmg Coa Reductase ◽

Cholesterol Levels ◽

Coa Reductase

Download Full-text

HMG-CoA reductase inhibition reverses LCAT and LDL receptor deficiencies and improves HDL in rats with chronic renal failure

AJP Renal Physiology ◽

10.1152/ajprenal.00074.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. F539-F544 ◽

Cited By ~ 26

Author(s):

K. Liang ◽

C. H. Kim ◽

N. D. Vaziri

Keyword(s):

Renal Failure ◽

Total Cholesterol ◽

Reductase Activity ◽

Plasma Cholesterol ◽

Ldl Receptor ◽

Hdl Cholesterol ◽

Hmg Coa Reductase ◽

Cholesterol Ratio ◽

Plasma Lcat ◽

Coa Reductase

Dyslipidemia is a prominent feature of chronic renal failure (CRF) and a major risk factor for atherosclerosis and the progression of renal disease. CRF-induced dyslipidemia is marked by hypertriglyceridemia and a shift in plasma cholesterol from HDL to the ApoB-containing lipoproteins. Several studies have demonstrated a favorable response to administration of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors (statins) in CRF. This study was intended to explore the effect of statin therapy on key enzymes and receptors involved in cholesterol metabolism. Accordingly, CRF ( nephrectomized) and sham-operated rats were randomized to untreated and statin-treated (rosuvastatin 20 mg·kg−1·day−1) groups and observed for 6 wk. The untreated CRF rats exhibited increased total cholesterol-to-HDL cholesterol ratio, diminished plasma lecithin:cholesterol acyltransferase (LCAT) and the hepatic LDL receptor, elevated hepatic acyl-CoA:cholesterol acyltransferase (ACAT), and no change in hepatic HMG-CoA reductase, cholesterol 7α-hydroxylase, or HDL receptor (SRB-1). Statin administration lowered HMG-CoA reductase activity, normalized plasma LCAT, total cholesterol-to-HDL cholesterol ratio, and hepatic LDL receptor but did not significantly change either plasma total cholesterol, hepatic cholesterol 7α-hydroxylase, total ACAT activity, or SRB-1 in the CRF animals. Statin administration to the normal control rats led to significant increases in plasma LCAT and hepatic LDL receptor, significant reductions of total cholesterol-to-HDL cholesterol ratio, hepatic HMG-CoA reductase activity, and cholesterol 7α-hydroxylase abundance with virtually no change in plasma cholesterol concentration. Thus administration of rosuvastatin reversed LCAT and LDL receptor deficiencies and promoted a shift in plasma cholesterol from ApoB-containing lipoproteins to HDL in CRF rats.

Download Full-text

Antioxidative and Inhibitory Effects of the Fruiting Body of Black Lingzhi Mushroom, Amauroderma rugosum (Agaricomycetes), on LDL Oxidation and HMG-CoA Reductase Activity

International Journal of Medicinal Mushrooms ◽

10.1615/intjmedmushrooms.2017024374 ◽

2017 ◽

Vol 19 (9) ◽

pp. 797-807 ◽

Cited By ~ 1

Author(s):

Chan Kam Seng ◽

Noorlidah Abdullah ◽

Norhaniza Aminudin

Keyword(s):

Fruiting Body ◽

Reductase Activity ◽

Ldl Oxidation ◽

Inhibitory Effects ◽

Hmg Coa Reductase ◽

Coa Reductase

Download Full-text

Effect of vitamin D3 derivatives on cholesterol synthesis and HMG-CoA reductase activity in cultured cells.

The Journal of Lipid Research ◽

10.1016/s0022-2275(20)38357-7 ◽

1989 ◽

Vol 30 (3) ◽

pp. 379-386

Author(s):

A K Gupta ◽

R C Sexton ◽

H Rudney

Keyword(s):

Vitamin D3 ◽

Cholesterol Synthesis ◽

Cultured Cells ◽

Reductase Activity ◽

Hmg Coa Reductase ◽

Coa Reductase

Download Full-text

The absolute rate of cholesterol biosynthesis in monocyte-macrophages from normal and familial hypercholesterolaemic subjects

Biochemical Journal ◽

10.1042/bj2190461 ◽

1984 ◽

Vol 219 (2) ◽

pp. 461-470 ◽

Cited By ~ 17

Author(s):

D D Patel ◽

C R Pullinger ◽

B L Knight

Keyword(s):

Cholesterol Synthesis ◽

Reductase Activity ◽

Cholesterol Biosynthesis ◽

Specific Radioactivity ◽

Density Lipoprotein ◽

Cellular Protein ◽

True Rate ◽

Hmg Coa Reductase ◽

Coa Reductase ◽

In Cells

The true rate of cholesterogenesis in cultured monocyte-macrophages was determined from the incorporation of [2-14C]acetate into cholesterol, using the desmosterol (cholesta-5,24-dien-3 beta-ol) that accumulated in the presence of the drug triparanol to estimate the specific radioactivity of the newly formed sterols. It was shown that this procedure could be successfully adapted for use with cultured monocytes despite the accumulation of other unidentified biosynthetic intermediates. In cells maintained in 20% (v/v) whole serum approx. 25% of the sterol carbon was derived from exogenous acetate. Cholesterol synthesis was as high in normal cells as in cells from homozygous familial hypercholesterolaemic (FH) subjects and accounted for 50% of the increase in cellular cholesterol. The addition of extra low-density lipoprotein (LDL) reduced cholesterol synthesis, apparently through a decrease in the activity of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase). When incubated in lipoprotein-deficient serum some cells did not survive, but those that remained showed a normal increase in protein content; the amount of cellular protein and cholesterol in each well did not increase and cholesterol synthesis was reduced by over 80%. HMG-CoA reductase activity fell less dramatically and the proportion of sterol carbon derived from exogenous acetate increased, suggesting that the low rate of cholesterogenesis with lipoprotein-deficient serum was due to a shortage of substrate. The results indicate that under normal conditions monocyte-macrophages obtain cholesterol from endogenous synthesis rather than through receptor-mediated uptake of LDL, and that synthesis together with non-saturable uptake of LDL provides the majority of the cholesterol required to support growth.

Download Full-text

The roles of different protein kinases and of calmodulin in the effects of Ca2+ mobilization on 3-hydroxy-3-methylglutaryl-CoA reductase activity in isolated rat hepatocytes

Biochemical Journal ◽

10.1042/bj2730485 ◽

1991 ◽

Vol 273 (2) ◽

pp. 485-488 ◽

Cited By ~ 6

Author(s):

V A Zammit ◽

A M Caldwell

Keyword(s):

Protein Kinase ◽

Reductase Activity ◽

Rat Hepatocytes ◽

Total Activity ◽

Isolated Hepatocytes ◽

Isolated Rat Hepatocytes ◽

Hmg Coa Reductase ◽

Lysosomal Proteolysis ◽

Dependent Protein ◽

Coa Reductase

The roles of protein kinase C, Ca2+/calmodulin-dependent protein kinase and AMP-activated protein kinase in the phosphorylation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase induced by Ca2(+)-mobilizing conditions in isolated hepatocytes were investigated. Only partial evidence for the involvement of AMP-activated kinase was found. Antagonism of calmodulin action prolonged the decrease in expressed/total activity ratio induced by vasopressin plus glucagon. Protease inhibitors active against Ca2(+)-dependent cytosolic proteases or lysosomal proteolysis did not attenuate the loss of total HMG-CoA reductase induced by glucagon plus vasopressin, but calmodulin antagonists largely prevented this effect.

Download Full-text