HMG-CoA Reductase Inhibitor, Simvastatin Is Effective in Decreasing Degree of Myocarditis by Inhibiting Metalloproteinases Activation

Background: Acute myocarditis often progresses to heart failure because there is no effective, etiology-targeted therapy of this disease. Simvastatin has been shown to be cardioprotective by decreasing matrix metalloproteinases’ (MMPs) activity. The study was designed to determine whether simvastatin inhibits MMPs activity, decreases the severity of inflammation and contractile dysfunction of the heart in experimental autoimmune myocarditis (EAM). Methods: Simvastatin (3 or 30 mg/kg/day) was given to experimental rats with EAM by gastric gavage for 21 days. Then transthoracic echocardiography was performed, MMPs activity and troponin I level were determined and tissue samples were assessed under a light and transmission electron microscope. Results: Hearts treated with simvastatin did not show left ventricular enlargement. As a result of EAM, there was an enhanced activation of MMP-9, which was significantly reduced in the high-dose simvastatin group compared to the low-dose group. It was accompanied by prevention of myofilaments degradation and reduction of severity of inflammation. Conclusions: The cardioprotective effects of simvastatin in the acute phase of EAM are, at least in part, due to its ability to decrease MMP-9 activity and subsequent decline in myofilaments degradation and suppression of inflammation. These effects were achieved in doses equivalent to therapeutic doses in humans.

The HMG-CoA Reductase Inhibitor Activities of Soy Protein Hydrolysates from Papain Hydrolysis

The search for an HMG-CoA reductase inhibitor agent as a safe and inexpensive alternative treatment for hypercholesterolemia has been carried out using soy protein hydrolysates as one of the bioactive peptide sources. This study was conducted to explore the potency of soy protein hydrolysates as an anti hypercholesterolemia agent by an in vitro assay, through the inhibition capacity of the HMG-CoA (3-hydroxy-3-methyl glutaryl-coenzyme A) reductase enzyme as a key component of cholesterol biosynthesis. Sample preparation started with soy protein isolation through acid precipitation and separated by centrifugation. The samples were analyzed the proximate content and hydrolyzed by papain enzyme at concentration 0.2% (w/v), for 0-6 hours and at 37, 50, and 55 oC. The protein hydrolysates were subsequently evaluated for hydrolysis degree (% DH), hydrolysates profile with SDS-PAGE (Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis), and anti-cholesterol assay through HMG-CoA reductase inhibition tests. The sample with the highest inhibition activity was fractionated using gel filtration chromatography (Sephadex G-10) and the molecular weight of fractions was characterized by LCMS QTOF (Liquid Chromatography-Mass Spectrometry Quadrupole Time-of-Flight) for molecular weight determination. The results indicated the optimum hydrolysis conditions of soy protein isolates were obtained at 3 hours incubation, at 50 °C with DH 33.39% and the inhibition value was 95.65% (protein concentration 39.21 μg / mL). LCMS data showed the molecular weight of fractionated peptides were 1514 and 2029 Da. We assumed that both peptides have the same affinity as previous peptides in inhibiting HMG-CoA reductase.

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

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.

Role of HMG-COA reductase inhibitor and allium sativum on lipid profile in diabetic dyslipidemic patients: A comparative study.

Objectives: To evaluate the changes in lipid profile in patients with diabetic dyslipidemia using lipid lowering drug, simvastatin and herbal product allium sativum. Study Design: Clinical trial. Setting: Surgeon Munawar Memorial Hospital, Karachi. Period: 1st January 2017 to 30th April 2017. Material & Methods: The study was designed to assess the effects of hmg-coa reductase inhibitor (simvastatin) and allium sativum on lipid profile in patients with diabetic dysplipidemia. The exclusion criteria included lactating/pregnant women’s, renal, liver and established coronary artery disease. Results: Sixty patients with abnormal lipid profile were included in the study (age 30-60 years). Patients were divided into two groups (30 patients each). Group a was orally administered with product of simvastatin (20 mg)/day for 04 months and in group b, patients were orally administered with herbal product of allium sativum (300 mg)/day for 04 months. Conclusion: On the basis of this study it is observed that allium sativum as well as simvastatin tablets both reduce total cholesterol, low density lipoprotein cholesterol (ldl-c) and increase high density lipoprotein cholesterol (hdl-c).