scholarly journals Hesperidin Interaction with HMG-CoA-Reductase Enzyme in Hypercholesterolemia: A Study in Silico

2021 ◽  
Vol 17 (2) ◽  
pp. 173
Author(s):  
Annisa Rizqi Dwi Oktaviani ◽  
Veronica Shania Aprillia ◽  
Eko Suhartono ◽  
Noer Komari
Keyword(s):  
Amino Acid ◽  
In Silico ◽  
Orange Peel ◽  
Data Bank ◽  
Receptor Protein ◽  
Hmg Coa Reductase ◽  
Protein Target ◽  
Natural Ligand ◽  
Cholesterol Levels ◽  
Coa Reductase

Abstract: Dyslipidemia is a degenerative disease occurred with increased levels of fat and cholesterol levels in blood. One of the proteins used as anti-cholesterol is an HMG-CoA-Reductase. Hesperidin in orange peel can reduce cholesterol levels by interacting with HMG-CoA-Reductase. To prove this, an in silico method was used by using swissdock.ch (http://swissdock.ch/docking#). The receptor protein in dyslipidemia was obtained from the RCSB Protein Data Bank (https://www.rcsb.org) namely HMG-CoA-reductase receptor with code PDB: 1HW9. The natural ligand, hesperidin, was obtained from PubChem with code: 10621 (https://pubchem.ncbi.nlm.nih.gov/). Protein was prepared by omitting the natural ligand residues present in the protein. Ligand and protein preparations were used by the chimera 1.15. The result of this study indicated that the interaction of hesperidin with several amino acid recidues was predicted to provide inhibitory activity on HMG-CoA reductase as the protein target. Inhibition of HMG-CoA reductase will reduce mevalonate synthesis so that cholesterol levels will decrease.  Keywords: hesperidin, HMG-CoA-Reductase, cholesterol, dyslhahipidemia

scholarly journals Molecular cloning and sequence of a cholesterol-repressible enzyme related to prenyltransferase in the isoprene biosynthetic pathway.

1987 ◽  
Vol 7 (9) ◽  
pp. 3138-3146 ◽  
Author(s):  
C F Clarke ◽  
R D Tanaka ◽  
K Svenson ◽  
M Wamsley ◽  
A M Fogelman ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Amino Acid ◽  
Molecular Cloning ◽  
In Vitro Transcription ◽  
In Vitro Translation ◽  
Mrna Levels ◽  
Hmg Coa Reductase ◽  
Transcription System ◽  
Coa Reductase

Differential hybridization and molecular cloning have been used to isolate CR39, a cDNA which hybridizes to a 1.2-kilobase (kb) mRNA in rat liver. The level of CR39 mRNA was increased seven- to ninefold over normal levels by dietary cholestyramine and mevinolin and decreased about fourfold compared with normal levels by cholesterol feeding or administration of mevalonate. Similar changes in the mRNA levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and HMG-CoA synthase were observed under the various conditions. In vitro translation of either CR39 hybrid selected RNA or 1.2-kb CR39 RNA generated by an SP6 in vitro transcription system produced a polypeptide of 39,000 daltons. As deduced from the nucleotide sequence of a full-length CR39 cDNA, the rat CR39 polypeptide contained 344 amino acids and had a molecular weight of 39,615. The predicted amino acid composition and submit molecular weight of the rat CR39 were very similar to those of prenyltransferases isolated from chicken, pig, and human. The sequence of amino acid residues 173 through 203 in the rat CR39 polypeptide showed that 17 out of 30 matched an active-site peptide of avian liver prenyltransferase. Thus, alterations in the rate of cholesterogenesis resulted in the coordinate regulation of three mRNAs encoding HMG-CoA reductase, HMG-CoA synthase, and CR39, the latter being tentatively identified as prenyltransferase.

scholarly journals Purification, Characterization, and Cloning of a Eubacterial 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase, a Key Enzyme Involved in Biosynthesis of Terpenoids

1999 ◽  
Vol 181 (4) ◽  
pp. 1256-1263 ◽  
Author(s):  
Shunji Takahashi ◽  
Tomohisa Kuzuyama ◽  
Haruo Seto
Keyword(s):  
Amino Acid ◽  
Coenzyme A ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Gel Filtration ◽  
Ph Optimum ◽  
Hmg Coa Reductase ◽  
Apparent Homogeneity ◽  
Key Enzyme ◽  
Coa Reductase

ABSTRACT The eubacterial 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (EC 1.1.1.34 ) was purified 3,000-fold fromStreptomyces sp. strain CL190 to apparent homogeneity with an overall yield of 2.1%. The purification procedure consisted of (NH4)2SO4 precipitation, heat treatment and anion exchange, hydrophobic interaction, and affinity chromatographies. The molecular mass of the enzyme was estimated to be 41 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 100 to 105 kDa by gel filtration chromatography, suggesting that the enzyme is most likely to be a dimer. The enzyme showed a pH optimum of around 7.2, with apparent Km values of 62 μM for NADPH and 7.7 μM for HMG-CoA. A gene from CL190 responsible for HMG-CoA reductase was cloned by the colony hybridization method with an oligonucleotide probe synthesized on the basis of the N-terminal sequence of the purified enzyme. The amino acid sequence of the CL190 HMG-CoA reductase revealed several limited motifs which were highly conserved and common to the eucaryotic and archaebacterial enzymes. These sequence conservations suggest a strong evolutionary pressure to maintain amino acid residues at specific positions, indicating that the conserved motifs might play important roles in the structural conformation and/or catalytic properties of the enzyme.

scholarly journals Ameliorations in the Biomarker Indices of Dyslipidemia and Atherosclerotic Plaque by the Inhibition of HMG – CoA Reductase and Antioxidant Potential of Phytoconstituents of an Aqueous Seed Extract of Acacia Senegal (L.) Willd in Rabbits

2021 ◽  
Author(s):  
Jaykaran Charan ◽  
Priyanka Riyad ◽  
Heera Ram ◽  
Ashok Purohit ◽  
Sneha Ambwani ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
In Silico ◽  
Risk Index ◽  
Seed Extract ◽  
Atherogenic Index ◽  
Acacia Senegal ◽  
Hmg Coa Reductase ◽  
Coa Reductase

Abstract Background: The HMG-CoA inhibitor are used to control adverse cardiovascular event caused by Hypercholesterolemia and dyslipidaemia. The current study was aimed to evaluate the ability of phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd to inhibit HMG-CoA reductase and regress the formation of atherosclerotic plaque. Methods: The chemical fingerprinting of the test extract was assessed by LC-MS. Consequently, the assessments of in-vitro, in-vivo, and in-silico were performed by following the standard methods.Results: The in-vitro assessment of the test extract revealed 74.1 % inhibition potential of HMG-CoA reductase. In-vivo evaluations of the test extract indicated that treated hypercholesterolemic rabbits exhibited a significant (𝑃 ≤ 0.001) ameliorations in the biomarker indices of the dyslipidaemia, such as the atherogenic index, Castelli risk index (I&II), atherogenic coefficient along with lipid profile. Concomitantly, significant reductions were observed in the atherosclerotic plaque area and antioxidants. The in-silico study of molecular docking shown interactions capabilities of key phytoconstituents of the test extract with target protein of HMG-CoA reductase which further validated by the molecular dynamics through potentail energy, NPT, NVT, RSMD and others. Subsequently, the ADMET analysis shown ideal druggability. Conclusion: The results indicate that phytoconstituents of an aqueous seed extract of Acacia senegal (L.) Willd. could inhibit HMG-CoA reductase and improve the levels of antioxidants activity that may reduce symptoms associated with hypercholesterolemia.

scholarly journals Inhibition of HMG-CoA Reductase Activity from Active Compounds of Ginger (Zingiber officinale): In-Silico Study

2021 ◽  
Vol 1 (1) ◽  
pp. 32-38
Author(s):  
Rosario Trijuliamos Manalu ◽  
Imelia Omega Meheda ◽  
Cintya Octaviani
Keyword(s):  
In Silico ◽  
Cholesterol Metabolism ◽  
Raw Materials ◽  
Reductase Activity ◽  
Zingiber Officinale ◽  
Active Compounds ◽  
Hmg Coa Reductase ◽  
Conducting Research ◽  
Main Components ◽  
Coa Reductase

ABSTRAK   Koleterol merupakan salah satu dari lemak tubuh dalam asam lemak bebas dan ester, yang termasuk komponen utama selaput sel otak dan saraf. Namun, tidak jarang kolesterol menjadi penyebab penyakit terutama penyakit jantung yang terus meningkat setiap tahunnya di Indonesia. Sehingga perlu strategi pengobatan yang efektif dan aman dengan melakukan penelitian tanaman Indonesia sebagai upaya kemandirian bahan baku obat. Tujuan dari penelitian ini adalah untuk menentukan aktivitas penghambatan dari senyawa aktif tanaman Jahe pada HMG-KoA reduktase secara in-silico melalui penambatan molekul. Senyawa aktif yang digunakan dalam penelitian ini curcumin, capsaisin, gingerol, paradol, shogaol dilakukan docking molekuler menggunakan software PLANTS dengan tujuan untuk mengetahui score docking dan interaksi kelima senyawa terhadap enzim HMG-KoA reduktase yang berperan terhadap metabolism lemak/kolesterol. Senyawa pembanding yang digunakan adalah simvastatin dan atorvastatin yang merupakan obat lini pertama untuk pengobatan displipidemia. Hasil score docking menunjukkan bahwa kelima senyawa aktif yang digunakan sebagai ligan, menunjukkan score docking yang lebih rendah dibandingkan dengan ligan pembanding, sehingga kelima senyawa aktif ini mampu untuk menghambat biosintesis kolesterol atau kandidat obat baru pengganti simvastatin dan atorvastatin serta berpotensi sebagai dyslipidemia.   ABSTRACT Cholesterol is one of the body's fats in free fatty acids and esters, which are the main components of brain and nerve cell membranes. However, it is not uncommon for cholesterol to be the cause of disease, especially heart disease, which continues to increase every year in Indonesia. So it needs an effective and safe treatment strategy by conducting research on Indonesian plants as an effort to be independent of medicinal raw materials. The aim of this study was to determine the inhibitory activity of the active compound of Ginger plant on HMG-CoA reductase in-silico through molecular anchoring. The active compounds used in this study were curcumin, capsaicin, gingerol, paradol, shogaol. Molecular docking was carried out using PLANTS software with the aim of knowing the docking score and the interaction of the five compounds with the HMG-CoA reductase enzyme that plays a role in fat/cholesterol metabolism. Comparative compounds used are simvastatin and atorvastatin which are first-line drugs for the treatment of dysplipidemia.  

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

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.

Molecular cloning and sequence of a cholesterol-repressible enzyme related to prenyltransferase in the isoprene biosynthetic pathway

1987 ◽  
Vol 7 (9) ◽  
pp. 3138-3146
Author(s):  
C F Clarke ◽  
R D Tanaka ◽  
K Svenson ◽  
M Wamsley ◽  
A M Fogelman ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Amino Acid ◽  
Molecular Cloning ◽  
In Vitro Transcription ◽  
In Vitro Translation ◽  
Mrna Levels ◽  
Hmg Coa Reductase ◽  
Transcription System ◽  
Coa Reductase

Differential hybridization and molecular cloning have been used to isolate CR39, a cDNA which hybridizes to a 1.2-kilobase (kb) mRNA in rat liver. The level of CR39 mRNA was increased seven- to ninefold over normal levels by dietary cholestyramine and mevinolin and decreased about fourfold compared with normal levels by cholesterol feeding or administration of mevalonate. Similar changes in the mRNA levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and HMG-CoA synthase were observed under the various conditions. In vitro translation of either CR39 hybrid selected RNA or 1.2-kb CR39 RNA generated by an SP6 in vitro transcription system produced a polypeptide of 39,000 daltons. As deduced from the nucleotide sequence of a full-length CR39 cDNA, the rat CR39 polypeptide contained 344 amino acids and had a molecular weight of 39,615. The predicted amino acid composition and submit molecular weight of the rat CR39 were very similar to those of prenyltransferases isolated from chicken, pig, and human. The sequence of amino acid residues 173 through 203 in the rat CR39 polypeptide showed that 17 out of 30 matched an active-site peptide of avian liver prenyltransferase. Thus, alterations in the rate of cholesterogenesis resulted in the coordinate regulation of three mRNAs encoding HMG-CoA reductase, HMG-CoA synthase, and CR39, the latter being tentatively identified as prenyltransferase.

In silico Screening of Selected Flavanones for HMG CoA Reductase Inhibitory Activity

2020 ◽  
Vol 14 (5) ◽  
pp. 128-139
Author(s):  
Tan Ker Ying ◽  
Mohamed Saleem Abdul Shukkoor ◽  
Shaik Ibrahim Khalivulla
Keyword(s):  
Inhibitory Activity ◽  
In Silico ◽  
In Silico Screening ◽  
Hmg Coa Reductase ◽  
Coa Reductase
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