Inhibition Of HMG-CoA Reductase Activity Research Articles

In vitro and in silico studies of the potential cytotoxic, antioxidant, and HMG CoA reductase inhibitory effects of chitin from Indonesia mangrove crab (Scylla serrata) shells

This study aimed to characterize chitin extracted from Indonesia mangrove crab (Scylla serrata) shells, as well as to assess its in vitro cytotoxic, antioxidant, and HMG CoA reductase inhibitory potentials. In silico molecular docking, molecular dynamic, and ADMET prediction analyses were also carried out. Chitin was extracted from mangrove crab shells using deproteination and demineralization processes, Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) characterization are then performed. The MTT method was further tested in a study of cell viability, while in vitro method was used to assess HMG CoA reductase inhibitory and antioxidant activities. The extracted chitin was found to have a moderate level of cytotoxic and antioxidant activities. In vitro studies showed that it has an IC50 of 36,65 ± 0,082 μg/mL as an HMG CoA reductase inhibitor, and decreased enzyme activity by 68.733 % at 100 μg/mL as a concentration. Furthermore, in the in silico study, chitin showed a strong affinity to several targets, including HMG CoA reductase, HMG synthase, LDL receptor, PPAR-alfa, and HCAR-2 with binding energies of −5.7; −5.8; −3.6; −5.6; −4.6 kcal/mol, respectively. Based on the ADMET properties, it had non-toxic molecules, which were absorbed and distributed across the blood-brain barrier. The molecular dynamics (MD) simulation also showed that it remained stable in the active sites of HMG CoA reductase receptor for 100 ns. These results indicated that chitin from Indonesian mangrove crab shells can be used to develop more potent HMG CoA reductase inhibitor with antioxidant and cytotoxic activities for effective dyslipidemia therapy.

Lactic acid bacteria-malted vinegar: fermentation characteristics and anti-hyperlipidemic effect.

In this study, the fermentation characteristics and functional properties of lactic acid bacteria-malted vinegar (LAB-MV) were investigated during the fermentation period. Changes in the components (organic acids, free sugars, free amino acids, β-glucan, and gamma-aminobutyric acid (GABA)) of MV (BWAF0d, BWAF10d, BWAF20d) and LAB-MV (LBWAF0d, LBWAF10d, LBWAF20d) were analyzed according to the fermentation time. The amounts of β-glucan and GABA in LBWAF20d were greater than those in BWAF20d (122.00μg/mL, 83.06μg/mL and 531.00μg/mL, 181.31μg/mL, respectively). The ACE1 and HMG-CoA reductase inhibitory activities of LBWAF20d were 98.16% (1/20 dilution factor, DF) and 91.01% (1/25 DF), respectively. The lipid accumulation ratio and total cholesterol levels in HepG2 cells treated with LBWAF20d (1/200 DF) were reduced by 45.85% and 54.48%, respectively, compared to those in the untreated group. These results suggest that LAB-MV, which comprises barley wine manufactured from LAB and yeast, may improve hepatic lipid metabolism.

Cholesterol-lowering Effect of Protein Hydrolysates from Lemongrass (Cymbopogon citratus Stapf.)

Lemongrass (Cymbopogon citratus Stapf.) has been used in the Philippines for cooking and as an herb to treat a variety of ailments including hypertension and related cardiovascular diseases (CVDs). This study determined the potential of peptides obtained from the hydrolysis of lemongrass proteins to lower cholesterol in vitro and in an animal model. Proteins were extracted and digested in vitro simulating gastrointestinal conditions. Protein hydrolysates were collected and fractionated using RP-SPE column, and assayed for HMG-CoA reductase inhibitory activity against pravastatin as a control drug. Tannin-free protein extract (TFPE) and total protein hydrolysates (TPC) were administered to Sprague-Dawley rats maintained on a high-fat high-cholesterol diet for two weeks. TFPE yield was 0.03%. Simulated gastrointestinal digestion of the TFPE resulted in 74% yield of protein hydrolysates. Three fractions were obtained from RP-SPE elution of the protein hydrolysates, each with potent HMG-CoA inhibitory activity. The F3 fraction had the highest inhibition of HMG-CoA reductase (IC50 = 0.76 ppm, comparable to pravastatin (IC50 = 0.25 ppm). The inhibitory activity of the fractions was further confirmed through significant serum cholesterol reduction (p < 0.05) in Sprague-Dawley rats. Thus, protein hydrolysates from lemongrass have potential cholesterol-lowering effects in vitro through HMG-CoA reductase inhibition and in vivo through significant reduction of cholesterol levels in an animal model. Protein hydrolysates from lemongrass dietary proteins may serve as promising functional foods for the prevention of CVD risk.

Of Ethanol Extract of Cinnamon Bark (Cinnamomum burmanii) on the Lipid Profile and Malondialdehyde of Dyslipidemic Rats

Dyslipidemia is a risk factor for atherosclerosis. Dyslipidemia conditions and malondialdehyde (MDAs) increased can cause oxidative stress. Cinnamon contains antioxidant compounds that have a hypolipidemic effect. This study aimed to determine the effect of cinnamon bark ethanol extract on triglycerides, total cholesterol, LDL, HDL, and MDA in dyslipidemic rats. In this study, rats were divided into five groups, a negative control group: which received standard feed, a positive control group: which received a high-fat diet and PTU, the groups that received a high-fat diet, PTU, cinnamon bark ethanol extract (EECB) 125 mg/Kg BW, 250 mg/Kg BW, 500 mg/Kg BW. The results of the analysis showed a decrease in triglyceride levels in all groups given EECB (p <0.05). Total and LDL cholesterol levels decreased in the 125 mg/Kg BW EECB group, and malondialdehyde decreased in the 500 mg/Kg BW EECB group (p <0.05). HDL levels did not increase. The ethanol extract of cinnamon bark was able to improve lipid profiles because it contains cinnamaldehyde and quercetin that can inhibit HMG CoA reductase activity, as well as flavonoids, tannins, and cinnamate which are able to reduce triglyceride and MDA levels.
 Keywords: cinnamon, dyslipidemia, malondialdehyde, lipid profile.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity of Indonesian Cajanus cajan leaves and Zingiber officinale extracts

One indicator of antihypercholesterolemic candidates is their inhibitory activity on 3hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase enzyme. This study aimed to analyze the HMG-CoA reductase inhibitory activities of Cajanus cajan leaves, Zingiber officinale var Amarum and Zingiber officinale var Rubrum. C. cajan leaves and two types of Z. officinale were extracted using the maceration method with three solvents: distilled water, 70% ethanol and 96% ethanol. All nine types of resulted extracts were then analyzed for bioactive compounds and tested for the HMG-CoA reductase inhibitory activity using the HMG-CoA reductase analysis kit (BioVision’s K588-100). It was carried out in vitro using a colorimetric microplate reader with a wavelength of 340 nm at 37°C. The results showed that the extracts contained flavonoids, tannins, saponins and steroids. The nine extracts showed inhibitory activities on the HMG-CoA reductase enzyme. The three extracts showed the highest inhibitory activity; 70% ethanolic Z. officinale var Amarum extract (47.87%), aqueous Z. officinale var Rubrum extract (40.62%) and 70% ethanolic C. cajan leaves extract (39.38%). These results indicate that the three extracts have a medium inhibitory level of HMG-CoA reductase. The study suggested that the three types of extracts could be used as antihypercholesterolemic candidates such as antihypercholesterolemic functional food.

Molecular docking studies of Triphala with catalytic portion of HMG-CoA reductase enzyme

Introduction: Triphala, consisting of three fruits, Phyllanthus emblica L. (Phyllanthaceae), Terminalia bellirica (Gaertn.) Roxb. (Combretaceae), and T. chebula Retz, is a well-recognized Ayurvedic herbal formulation, used for various therapeutic purposes, including the treatment of dyslipidemia. Inhibitory activity against 3‑hydroxy‑3‑methylglutaryl‑coenzyme A (HMG‑CoA) reductase, a rate-limiting enzyme in the endogenous cholesterol synthesis pathway, is an essential target for the management of hypercholesterolemia. This in silico study aimed to investigate the HMG-CoA reductase inhibitory activity of the phytochemical compounds derived from Triphala formulation by employing molecular docking analysis. Methods: Ten phytochemical constituents of Triphala formulation were selectively used for docking study by using the HMG-CoA reductase template (PDB: 1HWK). Docking analysis was performed using AutoDock 4.2. The candidates were ranked by the binding energy parameters. Results: From the docking studies, the phytochemical compounds with HMG-CoA reductase inhibition could be classified into 4 groups, including phytosterols, polyphenols, tannins, and flavonoids. Beta-sitosterol exhibited the highest binding affinity to HMG-CoA reductase with a binding energy of -7.75 kcal/mol. Conclusion: These 10 phytochemical compounds in Triphala potentially exert their cholesterol-lowering effects via inhibition against HMG-CoA reductase. Nonetheless, further in vitro and in vivo experiments should be conducted subsequently to confirm this finding.

Inhibition of HMG-CoA Reductase Activity by Kersen Leaves (Muntingia calabura L.) to Prevent Hypercholesterolemia

Background: Hypercholesterolemia is a condition of total cholesterol level >200 mg/dL and LDL >130 mg/dL. HMG-CoA (3-hydroxy-3-ethylglutaryl-coenzyme A) reductase is an enzyme that has a role in cholesterol biosynthesis. Hence, inhibition of this enzyme led to the decrement of cholesterol level. The extract of Kersen leaves (Muntingia calabura L.) is known to contain flavonoids, terpenoids, steroids, tannins, phenolic, and alkaloids. Flavonoids work by inhibiting the HMG-CoA reductase activity, so that mevalonate cannot be formed and thus decrease the cholesterol synthesis. Objectives: The present study aimed to determine the effect of Kersen leaves extract (M. calabura L.) in inhibiting the HMG-CoA reductase activity in vitro. Material and Methods: The study is a true experimental study with a post-test-only control group design. The independent variables were ethanol, methanol, and n-hexane extracts of Kersen leaves. Moreover, the percentage inhibition of the enzyme was the dependent variable. The test was conducted in vitro using UV-Vis spectrophotometry with pravastatin as a positive control. Results: The inhibitory effects of ethanol, methanol, n-hexane extracts of Kersen leaves, and pravastatin towards HMG-CoA reductase activity were 85.56%, 59.75%, 92.03%, and 99.58%, respectively. Post Hoc One-Way ANOVA showed that the p-values of pravastatin with ethanol, methanol, and n-hexane extracts were 0.687, 0.048, and 0.931, respectively. The n-hexane and ethanol extracts were potent for inhibiting the enzyme activity (p>0.05) comparable to pravastatin. Conclusion: The n-hexane and ethanol extracts of Kersen leaves could serve as a natural source of HMG-CoA reductase inhibitor to prevent hypercholesterolemia.

Design, synthesis, and biological evaluation of novel atorvastatin derivatives

Cardiovascular disease is the leading cause of death worldwide. High cholesterol level is a risk factor for coronary artery disease. Cholesterol production is regulated by the enzyme 3‑hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Statins, HMG-CoA reductase inhibitors, are often used as lipid-lowering drugs to prevent cardiovascular disease. Therefore, this study aimed to evaluate the inhibitory activity of several atorvastatin derivatives and assess their inhibitory activity against the HMG-CoA reductase enzyme. Atorvastatin derivatives S1, S2, and S3 were synthesized by acylation of the benzene ring of atorvastatin. Moreover, the amine group of atorvastatin was treated with ethanol and sulfuric acid, to provide atorvastatin-anthranilic acid derivatives (S4 and S5). An in silico docking study was performed on the HMG-CoA reductase (PDB ID: 1HWK), and it was observed that compound S3 with a propargyl functional group had the highest binding affinity (∆G= -6.8 kcal/mol). The obtained results showed that S3 compound could significantly inhibit HMG-CoA reductase activity compared to controls pravastatin and atorvastatin (P<0.05). The in vivo antihyperlipidemic activity results discovered that compound S3 increased HDL, and decreased cholesterol, LDL and triglyceride compared to the atorvastatin during 60 days of treatment (P < 0.05). Liver enzyme levels and rabbit liver histology study showed no toxicity for the S3 compound. Additionally, the S3 might be considered as an effective medicine in preventing atherosclerosis.

Antioxidant and 3-hydroxy-3-methylglutaryl Coenzyme A reductase inhibitory activities of some plant samples

The antioxidant activity capacities of some plants, and their inhibitory effects on the HMG-CoA reductase enzyme, the rate-determining enzyme of cholesterol synthesis, were investigated in our study. Antioxidant activity capacity and inhibitory effect of the HMG-CoA reductase enzyme were detected in all plant extracts used in our research. The results obtained determined that both antioxidant activity and % inhibition values of HMG-CoA reductase enzyme increased as the plant extracts concentration increased. The strongest ABTS and DPPH radical scavenging activities were exhibited by pomegranate fruit extract (IC50= 1.07 ±0.04 mg/mL and IC50= 0.39 ±0.01 mg/mL, respectively). At the same time, lemon had the strongest DMPD radical scavenging activity (IC50= 9×10-4 ±6×10-5 mg/mL). The best HMG-CoA reductase inhibitory activity was observed in persimmon fruit extract (IC50= 0.71 ±0.18 µg/mL). The inhibitory power of this extract was much higher than that of the enzyme’s standard inhibitor, Atorvastatin (IC50 = 1.76 ±0.12 µg/mL). The extracts' potent antioxidant and inhibitory properties can be attributed to the rich phytochemical composition of plant extracts. Thus, it may be a potential source of new bioactive compounds effective against oxidative stress, hypercholesterolemia and cardiovascular complications.

HMG-CoA Reductase Inhibitory Activity Potential of Iota-, Kappa-, and Lambda-carrageenan: A Molecular Docking Approach

HMG-CoA reductase is an essential enzyme responsible for the biosynthesis of cholesterol. Hyperactivity of HMG-CoA reductase will increase cholesterol production, leading to the elevation of blood cholesterol levels. Inhibition of HMG-CoA reductase is one way to block cholesterol biosynthesis to lower blood cholesterol levels. This study evaluated the inhibitory potential of iota-, kappa-, and lambda-carrageenan against HMG-CoA reductase. The study was undertaken by in silico method using a molecular docking approach via Autodock 4.2 assisted by ADT graphical user interface. HMG-CoA reductase co-crystal structure was used as the target, and iota-, kappa-, and lambda-carrageenan as the test ligands. The result revealed that iota- and lambda-carrageenan possess an excellent affinity to HMG-CoA reductase with the free binding energy of -12.44 and -11.87 kcal/mol and Ki value of 0.765 and 2.01 nM, respectively, which is found to be better than Simvastatin and the native ligand. The compounds' chemical properties influenced the molecules' molecular interactions affecting their affinity. The number of SO4 groups is assumed to affect the HMG-CoA reductase inhibitory activity of iota-, kappa-, and lambda-carrageenan.&#x0D; KEYWORDS: iota-, kappa-, and lambda-carrageenan; HMG-CoA reductase; inhibitory activity; molecular docking

Evaluation of hypolipidemic, antioxidant, atherogenic index and cardiac risk suppressing effects of unpolished maniki madhuri rice extract and HPLC analysis of phenolics compounds

Intake of whole grain has received huge consideration in recent times. This study aimed to investigate the hypolipidemic, antioxidant, and cardiac risk suppressing effect of whole rice extract of maniki madhuri joha rice (GI tagged) of Assam, India. In vitro antioxidant, HMG-CoA reductase enzyme inhibition assay, cholesterol esterase (CEase) inhibitory assay and antilipase activities of extracts of maniki madhuri were performed. Hyperlipidemia in experimental rats was induced by administering a high fat-high sugar diet for 45 days. Ethanol extract of whole rice (EtOH-MM) and atorvastatin were given orally to the animals in designated groups, and biochemical parameters were evaluated. Further, the presence of phenolic compounds was also estimated using the HPLC method. Extracts displayed concentration-dependent in vitro antioxidant, HMG-CoA reductase inhibitory and pancreatic lipase inhibitory activity. EtOH-MM exhibited strong CEase inhibitory activity (IC50 = 91.60 μg/ml). EtOH-MM at the dose of 200 and 400 mg/kg significantly ameliorated lipid parameters and the level of liver function marker enzymes to near normal. The lactate dehydrogenase and creatine kinase-NAC levels in EtOH-MM (400 mg/kg) group were 680.1 and 360.3 U/L, significantly less than the disease control group. C-reactive protein and lipoprotein a were significantly reduced in EtOH-MM treated group Ratio of ApoB/ApoA1 increased in the disease control group, which was reduced significantly in the standard and EtOH-MM treated group. The atherogenic index, atherogenic coefficient and cardiac risk ratio were decreased, while the cardioprotective index was increased in EtOH-MM treated group. Ten phenolic compounds i.e., gallic acid, caffeic acid, ferulic acid, p-coumaric acid, sinapic acid, o-coumaric acid, t-coumaric acid, rosamarinic acid, chlorogenic acid, phytic acid is quantified in maniki madhuri rice. The present study provided important evidence that consuming unpolished whole-grain of MM might be beneficial in managing hyperlipidemia and preventing associated cardiac complications.

Anti-inflammatory, cytotoxicity and antilipidemic properties: novel bioactivities of true cinnamon (Cinnamomum zeylanicum Blume) leaf

BackgroundThe leaf of Ceylon cinnamon (true cinnamon) is traditionally claimed for a variety of health benefits. However, reported scientific information is scanty and needs urgent attention for value addition.MethodsEthanolic (95%) and Dichloromethane:Methanol (DM, 1:1 v/v) leaf extracts of Ceylon cinnamon were evaluated for a range of medically important bioactivities namely anti-inflammatory [nitric oxide scavenging activity (NOSA), superoxide scavenging activity (SCA), COX1 and COX2 inhibition], growth inhibition & cytotoxicity against MCF7, HePG2 and AN3CA carcinoma cell lines, glutathionase-S-transferase (GST) inhibition and antilipidemic (anti-HMG-CoA reductase, anti-lipase, anti-cholesterol esterase, and cholesterol micellization inhibition) properties in vitro (n = 3). Further, a range of bioactive compounds in both leaf extracts was also quantified (n = 3).ResultsBoth leaf extracts had all the investigated bioactive compounds and possessed moderately potent bioactivities compared to the reference drugs used in the study. Ethanolic leaf extract (ELE) exhibited the highest activities (IC50: μg/mL) for NOSA (40.26 ± 0.52), SCA (696.24 ± 40.02), cholesterol esterase inhibition (110.19 ± 1.55), cholesterol micellization inhibition (616.69 ± 7.09), GST inhibition (403.78 ± 2.70) and growth inhibition (GI50: 144.84 ± 1.59-269.00 ± 0.51) & cytotoxicity (LC50: 355.44 ± 9.38-717.71 ± 23.69) against studied cancer cell lines. In contrast, COX1 & COX2 (IC50: 6.62 ± 0.85 and 44.91 ± 3.06 μg/mL) and HMG-CoA reductase & lipase inhibitory activities (36.72 ± 4.74 and 19.71 ± 0.97% inhibition at 200 and 600 μg/mL) were highest in DM extract. ELE also showed the highest quantities (0.81 ± 0.06-104.38 ± 1.79) of tested compounds (mg/g extract) where eugenol was the highest and gallic acid was the lowest among quantified.ConclusionBoth leaf extracts of Ceylon cinnamon had all the tested bioactive compounds and possess all the investigated bioactivities. This is the 1st study to report all the investigated bioactivities of the leaf of Ceylon Cinnamon.

Modulation of obesity associated metabolic dysfunction by novel lipophilic fraction obtained from Agaricus bisporus

AimThe present study aimed to prepare a novel lipophilic fraction rich in fat soluble bioactive from Agaricus bisporus and investigated its impact through in vitro and in vivo assessments since the prospective biological activities of fat soluble components from mushrooms are limited. MethodsErgosterol concentrate fraction (ECF) preparation followed by subsequent characterization of the extract using various analytical techniques (HPLC-UV, Mass spectroscopy, NMR). Furthermore, the fraction has been evaluated for antioxidant activity, DNA protection ability, hypolipidemic properties by in vitro specific enzyme inhibition and in vivo animal model (C57BL/6). Key findingsThe fraction majorly contains ergosterol (504 mg/100 g dw) and linoleic acid (71.92 %). In vitro studies showed that the fraction limited free radicals induced DNA damage, exhibited significant free radical scavenging activities (IC50 of DPPH 15.64; ABTS 8.28 mg/ml), and inhibited HMG-CoA reductase activity (IC50 5.03 mg/ml). Further, in vivo study showed that ECF treatment significantly (p < 0.05) improved insulin sensitivity (reduced plasma glucose & insulin, increased adiponectin) and reduced inflammatory markers (CRP & TNF-α) in comparison to high fat fed mice. Furthermore, ECF has significantly reduced plasma lipid profile and accumulation of lipids in liver. This could be due to down regulation of mRNA expression of lipogenic transcription factors such as SREBP-1c and SREBP-2, and key lipogenic enzyme ACC. Moreover, ECF treatment has suppressed protein expression of FAS, induced cholesterol clearance by enhancing LDL-R protein expression. SignificanceThe present work for the first time evaluated the synergistic potential of ergosterol and linoleic acid to improve antioxidant defense system and ameliorate obesity associated metabolic dysfunction.

Comprehensive study of chemical composition and biological activity of Thymus pubescens Boiss. et Kotschy ex Čelak.

The use of Thymus species amongst the public and their importance in the scientific world is increasing day by day. In addition to being consumed as tea and spice, Thymus species are used as folk medicine for respiratory, digestive, skin, circulatory, genital, nervous, visual and urinary diseases. In this study, it was aimed to examine the essential oil and ethanol extract of the root and aerial parts of Thymus pubescens Boiss. et Kotschy ex Celak in the terms of their biological activity and chemical content. The phenolic content of the species was determined by LC-MS/MS, while triterpenoid content, the chemical composition of the essential oil as well as flavour was determined by GC–MS. In addition, their antioxidant and cytotoxic activities, as well as acetyl- (AChE) and butyrylcholinesterase (BChE), urease, tyrosinase, elastase, collagenase, HMG-CoA reductase and angiotensin-converting enzyme (ACE) inhibitory activities were studied. Thymol (53.33%) was determined as the major component in the essential oil, while β-fenchyl alcohol (43.87%) was determined as the major component of the flavour. According to the LC-MS/MS and GC–MS results, it was found that especially the aerial parts of the species have a high amount of rosmarinic acid (3875.76 µg analyte/g extract), quinic acid (2392.55), naringenin (970.39), oleanolic (92785.96) and ursolic (63373.32) acids. The essential oil of T. pubescens species was observed to show high activity in four antioxidant assays, e.g. inhibition of lipid peroxidation, DPPH and ABTS radical scavenging activity as well as CUPRAC, while the ethanol extracts showed moderate antioxidant activity. In enzyme inhibition assays, the aerial parts exerted marked BChE, elastase, and collagenase inhibitory activities (92.43±1.28%, 42.59±0.56, and 48.61±0.39 at 100 µg/mL, respectively). On the other hand, AChE, urease, tyrosinase, HMG-CoA reductase and ACE inhibitory activities of all extracts were from low to moderate levels. In particular, the aerial parts of the species displayed a high cytotoxic effect (vitality%: 6.82±0.01 at 200 µg/mL) in breast cancer (MCF-7) cell line. Due to its remarkable antioxidant capacity, high content of rosmarinic, oleanolic, and ursolic acids and especially BChE, elastase, and collagenase inhibitory activity, T. pubescens has the potential for using in food supplements, food preservatives, cosmetics, and pharmaceutical industries.

Sesamum indicum diet prevents hyperlipidemia in experimental rats

Cardiovascular diseases and metabolic complications caused by hyperlipidemia are the leading cause of death globally. In this study, the hypolipidemic potency of Sesamum indicum (SI) seeds was investigated. Of the thirty-five (35) male rats used in the study, five (5) were randomly selected for baseline measurements and thirty (30) were fed high fat diet (HFD) for four (4) weeks before random assignment into three (3) groups. The experimental group was treated with 50% SI seed, the positive control group was given a hypolipidemic drug, atorvastatin (5 mg/kg/day) while the untreated group served as the negative control. With SI administration, the dyslipidemia induced by the HFD consumption in the plasma and the investigated body organs was reversed to a comparable degree with that of atorvastatin treatment. Taken together, this study demonstrates the hypolipidemic potency of SI in ameliorating hyperlipidemia and its associated complications, facilitated by the inhibition of HMG-CoA reductase activity.

HMG-COA REDUCTASE INHIBITORY ACTIVITY OF EXTRACT AND CATECHIN ISOLATE FROM UNCARIA GAMBIR AS A TREATMENT FOR HYPERCHOLESTEROLEMIA

The article describes a new idea of plant-based hypercholesterolemia treatment. Statins are commonly used for hypercholesterolemia treatment. Due to the side effects of statins, natural HMG-CoA reductase inhibitors plant-based are needed. Based on the affordability and less toxicity, the plant has increasing acceptability for treating ailments. The 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase is the key enzyme of the mevalonate pathway producing cholesterol. Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in a liver. As an Indonesian plant containing catechin, Uncaria gambir can reduce cholesterol in the blood through HMG-CoA reductase inhibitory activity. This study aims to investigate the potential antihypercholesterolemic of the extract and catechin isolate of Uncaria gambir. Gambier leaves were extracted in water. The catechin from gambier extract was isolated with ethyl acetate-hexane using column chromatography. Phytochemical analysis of extract and catechin isolate were conducted by high-performance liquid chromatography (HPLC). Antioxidant activity was tested using a 2.2-diphenyl-1-picrylhydrazyl (DPPH) assay with vitamin C as a positive control. The inhibitory activity of HMG-CoA enzymes was carried out enzymatically using an HMG-CoA reductase assay kit by spectrophotometric and simvastatin as a standard. The results showed that the catechin in the extract was 68.32% while in isolate - 96.74%. The extract's scavenging activity (IC50) was 6.2 μg/mL, catechin isolate was 2.4 μg/mL, and vitamin C was 4.1 μg/mL. The in-vitro assessment of HMG-CoA reductase activity indicated 73.12%; 97.46%; 85.74% inhibition by the extract, catechin isolate, and simvastatin, respectively. Catechin isolate from Uncaria gambir showed strong HMG-CoA reductase inhibitory activity offers a high potential for hypercholesterolemia treatment.

Effects of monacolin K-containing nutraceutical on cholesterol homeostasis re-establishment and CVD risk reduction in hypercholesterolemic subjects.

Hypercholesterolemia is caused by cholesterol homeostasis (CH) disruption, and it contributes to cardiovascular diseases pathogenesis and progression. Status of CH can be assessed by measuring serum concentrations of non-cholesterol sterols (NCS) which serve as cholesterol synthesis and absorption surrogate markers. Monacolin K, isolated from red yeast rice, influences cholesterol synthesis by inhibiting HMG-CoA reductase activity and reduces serum total cholesterol (TC) concentration. This longitudinal study included 30 hypercholesterolemic patients, with systematic coronary risk estimation (SCORE) values <10%, who received 3-months-long supplementation with nutraceutical mixture containing monacolin K, and vitamins C, B1 and K2. Serum NCS were quantified by HPLC-MS/MS method. Atherogenic indexes were calculated from lipid status parameters concentrations. Albumin degradation inhibition test was conducted to estimate in vitro anti-inflammatory activity of the nutraceutical mixture, whereas in vitro antioxidant activity was measured in serum enriched with prooxidants and antioxidants. TC, LDL-cholesterol (LDL-C), and triglycerides (TG) concentrations (p<0.001), as well as atherogenic indexes and SCORE values (p<0.001, p<0.01, respectively) were lowered following the supplementation. Concentrations of cholesterol synthesis markers were decreased (p<0.001), whereas levels of cholesterol absorption markers remained unchanged after the supplementation. Reduction in cholesterol synthesis went alongside reductions in lipid status parameters and atherogenic indexes. In vitro analyses showed certain anti-inflammatory and antioxidant activity of the nutraceutical. These results suggest that supplementation with monacolin K containing nutraceutical favorably influences lipid status parameters and atherogenic indexes by acting on cholesterol synthesis. Anti-inflammatory and antioxidant effects of this unique nutraceutical mixture may exhibit beneficial pleiotropic effects.

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

ABSTRAK&#x0D; &#x0D; 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.&#x0D; &#x0D; ABSTRACT&#x0D; 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.

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

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.

Anti-hyperlipidemic potential of natural product based labdane-pyrroles via inhibition of cholesterol and triglycerides synthesis

Hyperlipidemia is the clinical condition where blood has an increased level of lipids, such as cholesterol and triglycerides. Therefore controlling hyperlipidemia is considered to be a protective strategy to treat many associated diseases. Thus, a novel natural product derived pyrrole, and pyrazole-(E)-Labda-8(17),12-diene-15,16-dial conjugates with cholesterol and triglycerides synthesis inhibition potential was designed through scaffold hopping approach and synthesized via one-pot selective cycloaddition. Amongst the tested hybrids, 3i exhibited excellent activity against triglyceride and cholesterol synthesis with the percentage inhibition of 71.73 ± 0.78 and 68.61 ± 1.19, which is comparable to the positive controls fenofibrate and atorvastatin, respectively. Compounds 3j and 3k also exhibited the considerable potential of promising leads. The HMG CoA reductase inhibitory activity of the compounds was consistent with that of inhibitory activity of cholesterol synthesis. Compound 3i showed the highest inhibitory potential (78.61 ± 2.80) percentage of suppression, which was comparable to that of the positive control pravastatin (78.05 ± 5.4). Favourably, none of the compounds showed cytotoxicity (HepG2) in the concentration ranging from 0.5 to 100 μM.