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HMG-COA REDUCTASE INHIBITORY ACTIVITY OF EXTRACT AND CATECHIN ISOLATE FROM UNCARIA GAMBIR AS A TREATMENT FOR HYPERCHOLESTEROLEMIA
Abstract
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.
... Kandungan katekin dalam teh oolong memberikan hambatan pada enzim HMG-CoA Reduktase (Adelina, 2018). Katekin menghambat HMG-CoA reduktase dengan IC50 2,4 µg/mL (Nanang et al., 2021). HMG-CoA Reduktase adalah enzim yang mengubah HMG-CoA menjadi asam mevalonat yang menginisiasi sintesis kolesterol (Cherng, 2017). ...
Hyperlipidemia has an important role in the occurrence of cardiovascular, cerebrovascular, and peripheral vascular diseases. High cholesterol and LDL levels in the blood are at risk of causing various diseases such as atherosclerosis, pancreatic dysfunction and kidney disorders. Meanwhile, high triglyceride levels can cause impaired liver, pancreas and kidney function. Green bean, oolong tea and cinnamon are plants that can lower cholesterol levels. Oolong tea contains catechins, Green Bean contain phytosterols and cinnamon contains cinnamaldehyde. Determination of secondary metabolite levels of extracts was carried out using the Liquid Chromatography – Mass Spectroscopy (LC-MS) method. The activity test was carried out with 30 Wistar white rats which were divided into 6 test groups. The normal control group was treated with CMC-Na without feeding hypercholesterolemia, the positive control group was treated with simvastatin 0.4 mg/KgBW, the negative control group was treated with CMC-Na, the test groups 1, 2 and 3 were treated with cinnamon extract, oolong tea and green bean, respectively (150:50:50 mg/KgBW), (50:150:50 mg/KgBW) and (50:50:150 mg/KgBW). The detected metabolite content was cinnamaldehyde in cinnamon up to 10%, catechins in oolong tea up to 12% and stigmasterol in beans as much as 3.4%.The results obtained by test group 1 and test group 2 can reduce cholesterol and triglyceride levels (p0.05). All test groups had no significant effect on HDL and LDL levels.
Potentilla fulgens is known as Himalayan Cinquefoil and Lyngniangbru, rich in polyphenolic constituents and used as folk medicine by inhabitants of northeast India. This study intended to develop and validate a high‐performance thin‐layer chromatography method for the quantification of catechin in the Potentilla fulgens roots extract and explore its antioxidant potential, acetylcholinesterase, and hydroxymethylglutaryl‐coenzyme A reductase inhibition activity. The separation was achieved using the mobile phase of toluene: ethyl acetate: acetone: formic acid (6:6:6:1, v/v) in which the Potentilla fulgens roots extract delivered a condensed peak at R F 0.58 equivalent to catechin as a phytomarker. The amount of catechin in the Potentilla fulgens roots extract was found to be 2.01% w/w. Potentilla fulgens roots extract showed abundant 1,1‐diphenyl‐2‐picrylhydrazyl scavenging potential with half‐maximal inhibitory concentration values of 43.39 ± 1.43 μg/ml and inhibited acetylcholinesterase and hydroxymethylglutaryl‐coenzyme A reductase in a concentration‐dependent manner against (half‐maximal inhibitory concentration 74.78 ± 1.2 and 64.02 ± 1.7 μg/ml, respectively). The developed and validated high‐performance thin‐layer chromatography method is easy, accurate, and appropriate. These results support the use of Potentilla fulgens as folk medicine and suggest that Potentilla fulgens might be utilized as a rich source of natural antioxidants as well as acetylcholinesterase and hydroxymethylglutaryl‐coenzyme A reductase enzyme inhibitory agents.
This review provides an updated atomic-level perspective regarding the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR), linking the more recent data on this enzyme with a structure/function interpretation. This enzyme catalyzes one of the most important steps in cholesterol biosynthesis and is regarded as one of the most important drug targets in the treatment of hypercholesterolemia. Taking this into consideration, we review in the present article several aspects of this enzyme, including its structure and biochemistry, its catalytic mechanism and different reported and proposed approaches for inhibiting this enzyme, including the commercially available statins or the possibility of using dimerization inhibitors.
Inflammation and oxidative stress are believed to contribute to the pathology of several chronic diseases including hypercholesterolemia (elevated levels of cholesterol in blood) and atherosclerosis. HMG-CoA reductase inhibitors of plant origin are needed as synthetic drugs, such as statins, which are known to cause adverse effects on the liver and muscles.
Amaranthus viridis
(
A. viridis
) has been used from ancient times for its supposedly medically beneficial properties. In the current study, different parts of
A. viridis
(leaf, stem, and seed) were evaluated for potential anti-HMG-CoA reductase, antioxidant, and anti-inflammatory activities. The putative HMG-CoA reductase inhibitory activity of
A. viridis
extracts at different concentrations was determined spectrophotometrically by NADPH oxidation, using HMG-CoA as substrate.
A. viridis
leaf extract revealed the highest HMG-CoA reductase inhibitory effect at about 71%, with noncompetitive inhibition in Lineweaver-Burk plot analysis. The leaf extract showed good inhibition of hydroperoxides, 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), and ferric ion radicals in various concentrations.
A. viridis
leaf extract was proven to be an effective inhibitor of hyaluronidase, lipoxygenase, and xanthine oxidase enzymes. The experimental data suggest that
A. viridis
leaf extract is a source of potent antioxidant and anti-inflammatory agent and may modulate cholesterol metabolism by inhibition of HMG-CoA reductase.
Phenylpropanoids, particularly flavonoids have been recently suggested as playing primary antioxidant functions in the responses of plants to a wide range of abiotic stresses. Furthermore, flavonoids are effective endogenous regulators of auxin movement, thus behaving as developmental regulators. Flavonoids are capable of controlling the development of individual organs and the whole-plant; and, hence, to contribute to stress-induced morphogenic responses of plants. The significance of flavonoids as scavengers of reactive oxygen species (ROS) in humans has been recently questioned, based on the observation that the flavonoid concentration in plasma and most tissues is too low to effectively reduce ROS. Instead, flavonoids may play key roles as signaling molecules in mammals, through their ability to interact with a wide range of protein kinases, including mitogen-activated protein kinases (MAPK), that supersede key steps of cell growth and differentiation. Here we discuss about the relative significance of flavonoids as reducing agents and signaling molecules in plants and humans. We show that structural features conferring ROS-scavenger ability to flavonoids are also required to effectively control developmental processes in eukaryotic cells.
The main strategy for lowering blood cholesterol levels is through the inhibition of the NADPH-dependent HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase). The enzyme catalyses the reduction of HMG-CoA to mevalonate and this process is inhibited by statins that form the bulk of the therapeutic agents to treat high cholesterol since the 1970s. Newer drugs that are safer than statins are constantly being developed. The inhibition of candidate drugs to HMG-CoA reductase remains the mainstay of drug development research. The determination of the enzyme activity is important for the correct assessment of potency of the enzyme as well as determining the inhibition of potential therapeutic agents from the plant and microbial extracts. Also, this chapter covers the use of the popular four-parameter logistics model that can yield accurate estimation of the IC50 values of therapeutic agents and their 95% confidence intervals.
Introduction: Thuidium tamariscellum is a small creeping epiphytic moss growing on trunks and branches of trees as well as on moist shady rocky surface at high altitudes areas. Methods: The present study was undertaken to analyze the phytochemicals in the species and its antioxidant potentialities interms of DPPH, ABTS, H2O2, FRAP and metal chelating ability. Results: Total terpenoids level was remarkable. Interestingly, a concentration dependent free radical scavenging potential was noticed and was comparable with the synthetic antioxidant ascorbate. Further, the FTIR analysis of petroleum ether, chloroform, ethyl acetate, and methanol extract confirmed the presence of alcohols/phenols, primary, secondary amines, amides, alkanes, aldehydes, saturated aliphatic alkenes aromatics and aromatic amines, nitro compounds, carboxylic acids, esters, ethers, aliphatic amines, alkyl halides and carbonyls in the moss indicating the presence of medicinally important compounds like flavonoids, terpenoids and alkaloids in the various solvent extracts of the moss. Conclusion: The overall result of the present study showed that the moss is rich in important pharmaceutical compounds and was reflected as its antioxidant potential. Further studies are warranted to isolate, identify and purify the lead terpenoid present in the moss.
Plant products have always been considered for many important metabolic disorders due to its abundant medicinal properties. Alarming adverse effects of overuse of statins has been reported for patients with dyslipidemia. This study was aimed to identify compounds with potent antidyslipidemic property from selected plants and analyze them for their efficiency in binding with HMG-CoA reductase, a key enzyme in lipid metabolism. The docking studies indicate rutin as the best compound that can inhibit HMGCoA reductase as it had strong binding affinity to the enzyme. The molecular dynamics simulation studies confirmed the stability of the HMG-CoA reductase-rutin complex. RMSD, RMSF, Rg, H-bond results indicated that the HMG-CoA reductase-rutin complex is highly stable. Presently, statins are not preferred for individuals with pre-existing liver disease. Our study identified rutin as a promising lead compound which could be further developed into an anti-dyslipidemic molecule. Our results will be a good starting point for future experimental and clinical studies and if the results from such studies match international standards plant derived rutin might emerge as a good alternative to statins. This article is protected by copyright. All rights reserved.
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