Design, synthesis, and docking of highly hypolipidemic agents: Schizosaccharomyces pombe as a new model for evaluating α-asarone-based HMG-CoA reductase inhibitors

Argüelles, Nancy; Sánchez-Sandoval, Eugenia; Mendieta‐Moctezuma, Aarón; Villa‐Tanaca, Lourdes; Garduño‐Siciliano, Leticia; Jiménez, Fabiola; Cruz, María del Carmen; Medina‐Franco, José L.; Chamorro-Cevallos, Germán; Tamariz, Joaquı́n

doi:10.1016/j.bmc.2010.04.096

Cited by 34 publications

(18 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S6C). Conservation of this phenomenon in C. elegans, S. pombe, and mammals is especially important in view of the fact that the latter two types of organisms do have the branch of the mevalonate pathway that leads to sterol synthesis (1,21,22), which is lacking in C. elegans. In other words, the cytotoxic effects of statins are primarily related to mitochondria homeostasis even in organisms where the main output of the pathway is considered to be sterols.…”

Section: Resultsmentioning

confidence: 99%

The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathway

Rauthan

Ranji

Pradenas

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

119

137

View full text Add to dashboard Cite

Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme in the synthesis of cholesterol via the mevalonate pathway. This pathway also produces coenzyme Q (a component of the respiratory chain), dolichols (important for protein glycosylation), and isoprenoids (lipid moieties responsible for the membrane association of small GTPases). We previously showed that the nematode Caenorhabditis elegans is useful to study the noncholesterol effects of statins because its mevalonate pathway lacks the sterol synthesis branch but retains all other branches. Here, from a screen of 150,000 mutagenized genomes, we isolated four C. elegans mutants resistant to statins by virtue of gain-of-function mutations within the first six amino acids of the protein ATFS-1, the key regulator of the mitochondrial unfolded protein response that includes activation of the chaperones HSP-6 and HSP-60. The atfs-1 gain-of-function mutants are also resistant to ibandronate, an inhibitor of an enzyme downstream of HMG-CoA reductase, and to gliotoxin, an inhibitor acting on a subbranch of the pathway important for protein prenylation, and showed improved mitochondrial function and protein prenylation in the presence of statins. Additionally, preinduction of the mitochondrial unfolded protein response in wild-type worms using ethidium bromide or paraquat triggered statin resistance, and similar observations were made in Schizosaccharomyces pombe and in a mammalian cell line. We conclude that statin resistance through maintenance of mitochondrial homeostasis is conserved across species, and that the cell-lethal effects of statins are caused primarily through impaired protein prenylation that results in mitochondria dysfunction.

show abstract

Section: Resultsmentioning

confidence: 99%

The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathway

Rauthan

Ranji

Pradenas

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

119

137

View full text Add to dashboard Cite

show abstract

“…The blood samples were centrifuged at 3000 g for 15 min, and serum was collected to measure the lipid profile. The levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were determined as described by [17]. The atherogenic index was calculated using Friedewald's equation = (TC − HDL-c)/HDL-c.…”

Section: Hypolipidemic Studymentioning

confidence: 99%

Hypolipidemic Activity of Microwave-Dehydrated Mango (<i>Mangifera indica</i> L.) Powder in Mice Fed a Hypercholesterolemic Diet

Osorio-Esquivel¹,

Cortés-Viguri²,

Garduño‐Siciliano³

et al. 2014

JBiSE

Self Cite

View full text Add to dashboard Cite

The effect of dietary supplementation with mango (Mangifera indica L.) powder obtained by microwave dehydration was studied in normal and hypercholesterolemic mice. The phenolic profiles in methanolic extracts and antioxidant activities were determined using high-performance liquid chromatography and DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid) assays, respectively. The total phenolic content of microwavedehydrated mango powder was 1451.7 ± 26.7 μggallic acid equivalents/g dry weight. The main phenolic compounds identified were gallic acid, epicatechin, ferulic acid, and catechin. The antioxidant activity was 14.6% higher in microwave-dehydrated mango powder than in conventional mango powder. Mice were fed a hypercholesterolemic diet (1 g cholesterol/100g over 7 days). The hypercholesterolemic mice whose diets were supplemented with microwave-dehydrated mango powder showed a significant decrease (P ≤ 0.05) in total serum cholesterol compared to the hypercholesterolemic mice and the mice fed with conventional dehydrated mango powder. We O. Osorio-Esquivel et al. 810serum LDL-c (36.0%) and total cholesterol (43.3%) compared to the mice in hypercholesterolemic group. Notably, the atherogenic index was 72% lower in the microwave-dehydrated mango powder group compared to the hypercholesterolemic group. These results suggest that the biocompounds, such as polyphenols and dietary fiber, found in mango pulp might improve the lipid profile in mice fed a hypercholesterolemic diet.

show abstract

“…Further study indicated that activities of α -asarone in various animal seizure models [14] and against noise-stress effect [15] might be essentially accounted for by antioxidant properties. In addition, the hypolipidaemic [16–20] and radioprotective effects [21] of α -asarone were also been reported. Besides, β -asarone, which has toxic and sterilizing effects, shows potential for stored-product pest control [22].…”

Section: Introductionmentioning

confidence: 99%

Separation ofcis- andtrans-Asarone fromAcorus tatarinowiiby Preparative Gas Chromatography

Zuo

Yang

Zhang

et al. 2012

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

A preparative gas chromatography (pGC) method was developed for the separation of isomers (cis- and trans-asarone) from essential oil of Acorus tatarinowii. The oil was primarily fractionated by silica gel chromatography using different ratios of petroleum ether and ethyl acetate as gradient elution solvents. And then the fraction that contains mixture of the isomers was further separated by pGC. The compounds were separated on a stainless steel column packed with 10% OV-101 (3 m × 6 mm, i.d.), and then the effluent was split into two gas flows. One percent of the effluent passed to the flame ionization detector (FID) for detection and the remaining 99% was directed to the fraction collector. Two isomers were collected after 90 single injections (5 uL) with the yield of 178 mg and 82 mg, respectively. Furthermore, the structures of the obtained compounds were identified as cis- and trans-asarone by 1H- and 13C-NMR spectra, respectively.

show abstract

Design, synthesis, and docking of highly hypolipidemic agents: Schizosaccharomyces pombe as a new model for evaluating α-asarone-based HMG-CoA reductase inhibitors

Cited by 34 publications

References 50 publications

The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathway

The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathway

Hypolipidemic Activity of Microwave-Dehydrated Mango (<i>Mangifera indica</i> L.) Powder in Mice Fed a Hypercholesterolemic Diet

Separation ofcis- andtrans-Asarone fromAcorus tatarinowiiby Preparative Gas Chromatography

Contact Info

Product

Resources

About

Design, synthesis, and docking of highly hypolipidemic agents: Schizosaccharomyces pombe as a new model for evaluating α-asarone-based HMG-CoA reductase inhibitors

Cited by 34 publications

References 50 publications

The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathway

The mitochondrial unfolded protein response activator ATFS-1 protects cells from inhibition of the mevalonate pathway

Hypolipidemic Activity of Microwave-Dehydrated Mango (&lt;i&gt;Mangifera indica&lt;/i&gt; L.) Powder in Mice Fed a Hypercholesterolemic Diet

Separation ofcis- andtrans-Asarone fromAcorus tatarinowiiby Preparative Gas Chromatography

Contact Info

Product

Resources

About

Hypolipidemic Activity of Microwave-Dehydrated Mango (<i>Mangifera indica</i> L.) Powder in Mice Fed a Hypercholesterolemic Diet