scholarly journals Molecular Docking of Red Betel (Piper crocatum Ruiz & Pav) Bioactive Compounds as HMG-CoA Reductase Inhibitor

2021 ◽  
Vol 24 (3) ◽  
pp. 101-107
Author(s):  
Bella Fatima Dora Zaelani ◽  
Mega Safithri ◽  
Dimas Andrianto
Keyword(s):  
Molecular Docking ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Amino Acid Residues ◽  
Hmg Coa Reductase ◽  
Discovery Studio ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase

Cholesterol plaque buildup in artery walls occurs due to oxidation of Low-Density Lipoprotein (LDL) molecules by free radicals, which are a risk factor for coronary heart disease. Piper crocatum contains active compounds that can act as HMG-CoA reductase inhibitors, such as flavonoids, alkaloids, polyphenols, tannins, and essential oils. This study aimed to predict the potential of Piper crocatum extract and fraction compounds as HMG-CoA reductase inhibitors by investigating the ligand affinity to the HMG-CoA reductase enzyme. Ligand and receptor preparation was conducted using BIOVIA Discovery Studio Visualizer v16.1.0.15350 and AutoDock Tools v.1.5.6. Molecular docking used AutoDock Vina, while ligand visualization and receptor binding used PyMOL(TM) 1.7.4.5.Edu. The receptor used was HMG-CoA reductase (PDB code: 1HWK) with atorvastatin as a control ligand. Catechin, schisandrin B, and CHEMBL216163 had the highest inhibition with affinity energies of -7.9 kcal/mol, -8.2 kcal/mol, -8.3 kcal/mol, respectively. Amino acid residues that played a role in ligand and receptor interactions were Ser684, Asp690, Lys691, Lys692.

HMG-CoA reductase inhibitors suppress macrophage growth induced by oxidized low density lipoprotein

1997 ◽  
Vol 133 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Masakazu Sakai ◽  
Shozo Kobori ◽  
Takeshi Matsumura ◽  
Takeshi Biwa ◽  
Yoshihiro Sato ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Hmg Coa Reductase ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase

P-Glycoprotein Is Downregulated in KG1a Primitive Leukaemia Cells by LDL Cholesterol Deprivation and by HMG-CoA Reductase Inhibitors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4192-4192
Author(s):  
Laura Connelly-Smith ◽  
Joanne Pattinson ◽  
Martin Grundy ◽  
Shili Shang ◽  
Claire Seedhouse ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hmg Coa Reductase ◽  
Serum Free ◽  
Reductase Inhibitors ◽  
P Glycoprotein ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase ◽  
And Function

Abstract P-glycoprotein (pgp) is a membrane transporter encoded by the multidrug resistance (MDR1, ABCB1) gene. Pgp is a poor prognostic factor in elderly patients with acute myeloid leukaemia (AML). In addition to its role in drug efflux, pgp has been implicated in cellular cholesterol homeostasis. We investigated the effects of exogenous cholesterol removal on pgp expression and function. KG1a drug-naïve, primitive leukaemia cells were cultured in serum free medium with or without the addition of low density lipoprotein (LDL) cholesterol. After 72 hours pgp expression and function was assessed by flow cytometry and total cholesterol content of the KG1a cells was determined by the Amplex Red® cholesterol assay. The addition of clinically available cholesterol lowering agents, HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors to KG1a cells was also assessed. There was a 39% (SEM 8.3% P=0.03) decrease in pgp protein expression after 3 days of serum free culture without HMG-CoA reductase inhibitors. Message was decreased by 40% (P=0.01) and pgp function was also reduced by 40% (P=0.005). The addition of low density lipoprotein (LDL) cholesterol restored pgp expression to 86% of the basal value. The addition of a HMG-CoA reductase inhibitor to KG1a cells in serum free culture resulted in a further 26% (lovastatin, P=0.03) and 16% (pravastatin, P=0.05) reduction in pgp respectively. Lovastatin also significantly reduced cellular cholesterol levels by 47% (P=0.002) under serum free conditions. Furthermore, the toxicity of the pgp substrate drug daunorubicin was significantly enhanced following lovastatin pre-culture (P=0.04). We conclude that LDL/cholesterol contributes to pgp expression and chemoresistance in primitive leukaemia cells. The use of HMG-CoA reductase inhibitors may be of clinical value in lowering pgp expression in AML.

Lovastatin for Hypercholesterolemia

1988 ◽  
Vol 22 (7-8) ◽  
pp. 542-545 ◽  
Author(s):  
Frederick P. Zeller ◽  
Karen C. Uvodich
Keyword(s):  
Side Effects ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Dietary Control ◽  
Hmg Coa Reductase ◽  
Reductase Inhibitors ◽  
Familial Form ◽  
Percent Protein ◽  
Hmg Coa Reductase Inhibitors ◽  
Coa Reductase

Lovastatin is the first 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor approved for the treatment of primary hypercholesterolemia. It is indicated as adjunctive therapy to dietary control and should be initiated at 20 mg/d in the evening. With higher dosages, twice-daily dosing is preferred, particularly when the dosage reaches the maximum recommended 80 mg/d. Compared with other drugs available, lovastatin has been shown to have good efficacy and a low incidence of side effects. Limited pharmacokinetic information available from the manufacturer reports absorption ∼ 30 percent, protein binding > 95 percent, and a dual pathway for elimination through both urine (10 percent) and feces (83 percent). The drug has been clinically tested versus placebo and in combination with other cholesterol-lowering drugs. Lovastatin is effective in lowering total cholesterol and low-density lipoprotein cholesterol by 25–30 percent, with nonfamilial (hypercholesterolemic) patients responding better than those with the familial form of the disease. One percent of lovastatin patients have discontinued therapy because of intolerable side effects. The most common complaints are flatulence and diarrhea; more severe abnormalities include elevation of liver enzymes and an unclear propensity for producing lens opacities. The monthly cost to a patient taking 20 mg/d is approximately $44. Although the drug should be added to hospital formularies, long-term safety experience and competition from other HMG-CoA reductase inhibitors will determine lovastatin's final therapeutic role.

Toxicity of a Novel HMG-CoA Reductase Inhibitor in the Common Marmoset (Callithrix jacchus)

1994 ◽  
Vol 13 (5) ◽  
pp. 357-368 ◽  
Author(s):  
K. Owen ◽  
C.R. Pick ◽  
S.E. Libretto ◽  
M.J. Adams
Keyword(s):  
Recovery Period ◽  
Clinical Signs ◽  
Common Marmoset ◽  
Hmg Coa Reductase ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Chronic Study ◽  
Hmg Coa Reductase Inhibitor ◽  
Alveolar Proteinosis ◽  
Coa Reductase

1 GR95030X, a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, was administered daily to marmosets by gavage. In a Maximum Repeatable Dose (MRD) study, doses of up to 30 mg kg-1 day-1 were administered for 49 days. In a chronic study, animals received dosages equivalent to 0, 1, 2.5, 7,5 and 20 mg kg-1 day-1 for 204 or 205 days. Some animals were maintained without treatment for a recovery period of 29 or 30 days, 2 Clinical signs included poor coat condition, weakness with impaired coordination, lethargy and other behavioural changes, There was also alimentary disturbance, and some deaths occurred at doses of 20 mg kg-1 day-1 and above. 3 Adverse effects upon body weight were seen although some recovery was apparent after the cessation of treatment. 4 Serum cholesterol concentrations were reduced. Very large increases in serum ALT, AST and CK activities were recorded with CK-MM isoenzymes accounting for 80% or more of the total CK enzyme activity. 5 Treatment was associated with muscle fibre atrophy and a sarcolemmal response with little evidence of regeneration. Histological examination revealed vascular changes, glial proliferation and cell death in the brain, with no consistent distribution. Alveolar capillary congestion and alveolar proteinosis indicated that there may have been a reduction in cardiac function. 6 HMG-CoA reductase inhibitors have evident potential to cause myopathy in marmosets. This is believed to be the first report of such an effect.

Comparative Evaluation of the Safety and Efficacy of HMG-CoA Reductase Inhibitor Monotherapy in the Treatment of Primary Hypercholesterolemia

1995 ◽  
Vol 29 (7-8) ◽  
pp. 743-759 ◽  
Author(s):  
Irene Hsu ◽  
Sarah A Spinier ◽  
Nelda E Johnson
Keyword(s):  
Clinical Trials ◽  
Reductase Inhibitor ◽  
Efficacy And Safety ◽  
Comparative Efficacy ◽  
Hmg Coa Reductase ◽  
Primary Hypercholesterolemia ◽  
Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitors ◽  
Hmg Coa Reductase Inhibitor ◽  
Coa Reductase

Objective: To evaluate the comparative efficacy and safety of the 4 currently available hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, fluvastatin, lovastatin, pravastatin, and simvastatin, in the treatment of primary hypercholesterolemia. Data Sources: English-language clinical studies, abstracts, and review articles identified from MEDLINE searches and bibliographies of identified articles. Unpublished data were obtained from the Food and Drug Administration in accordance with the Freedom of Information Act. Study Selection: Placebo-controlled and comparative studies of HMG-CoA reductase inhibitor monotherapy in the treatment of primary hypercholesterolemia. Data Extraction: Pertinent studies were selected and the data were synthesized into a review format. Data Synthesis: The chemistry, pharmacology, and pharmacokinetics of the 4 HMG-CoA reductase inhibitors are reviewed. Clinical trials evaluating the hypocholesterolemic efficacy of the HMG-CoA reductase inhibitors are examined, and results on the comparative efficacy and safety of these agents are summarized. On a milligram-per-milligram basis, simvastatin is twice as potent as lovastatin and pravastatin. The hypocholesterolemic effects of fluvastatin appear to be approximately 30% less than that of lovastatin. In posttransplant patients receiving cyclosporine, safety has been documented for low doses of lovastatin and simvastatin, but when a higher dosage of an HMG-CoA reductase inhibitor is warranted, pravastatin should be considered the drug of choice because of a lower incidence of myopathy. Relevant data on the incidence of adverse effects are presented. Pertinent outcomes data from clinical trials evaluating the effect of HMG-CoA reductase inhibitors on atherosclerosis regression and coronary mortality, as well as published economic analyses of cholesterol-lowering agents, are summarized. Recommendations on the selection of an HMG-CoA reductase inhibitor in various clinical situations are provided. Conclusions: The literature supports the comparable safety and tolerability of all 4 currently available HMG-CoA reductase inhibitors. Therefore, the choice of an HMG-CoA reductase inhibitor should depend on the extent of cholesterol lowering needed to meet the recommended treatment goal established by the National Cholesterol Education Program. Direct comparative studies are needed to confirm the relative, long-term cost-effectiveness of the various HMG-CoA reductase inhibitors in the treatment of primary hypercholesterolemia.

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