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      Influence of extraction methods of bay leaves ( Syzygium polyanthum) on antioxidant and HMG-CoA Reductase inhibitory activity

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          Abstract

          Objective

          Bay leaf, one of the plants in Indonesia that has been shown to have activities to reduce cholesterol in the blood. HMG-CoA Reductase inhibition is one of many mechanisms in lowering the level of cholesterol in the blood. Here, we reported the inhibitory activity of HMG-CoA Reductase of bay leaves ethanol extracts that we suspected to be the mechanism of action of bay leaves in reducing cholesterol in the blood. In this research we also investigated the correlation between the inhibitory activities, the total phenol content and antioxidant activities of bay leaves ( Syzygium polianthum) ethanol extracts.

          Methods

          The inhibitory activity of HMG-CoA Reductase was determined kinetically at 340 nm using simvastatin as positive control. In vitro scavenging assays of 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric ion reducing antioxidant power (FRAP), and beta-carotene method were used to determine the antioxidant activities. The total phenolic content was determined by Folin-Ciocalteu's method.

          Results

          The IC 50 of bay leaves ethanolic extract obtained by percolation and soxhlet extraction method towards HMG-CoA Reductase enzyme activity were 49.50 ± 0.700 μg/mL and 15.50 ± 0.707 μg/mL, respectively, while the IC 50 of simvastatin was 0.00238 ± 0.00004 μg/mL. The antioxidant activity and total phenolic content of bay leaves ethanolic extract obtained by Soxhlet extraction method was higher compared to the percolation method (DPPH and beta-carotene assay results). The 3D linear analysis showed that there was a high correlation between the inhibition activities of HMG-CoA Reductase pattern of both extract types and the total phenol pattern and also the antioxidant pattern of these extracts.

          Conclusion

          The result showed that the bay leaves ethanolic extract have a potent activity to reduce the cholesterol serum level by inhibition of HMG-CoA Reductase activity. The activity was due to the phenolic compounds in the extracts as well as the antioxidant activity of the extracts.

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          Most cited references23

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          Structural mechanism for statin inhibition of HMG-CoA reductase.

          HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase (HMGR) catalyzes the committed step in cholesterol biosynthesis. Statins are HMGR inhibitors with inhibition constant values in the nanomolar range that effectively lower serum cholesterol levels and are widely prescribed in the treatment of hypercholesterolemia. We have determined structures of the catalytic portion of human HMGR complexed with six different statins. The statins occupy a portion of the binding site of HMG-CoA, thus blocking access of this substrate to the active site. Near the carboxyl terminus of HMGR, several catalytically relevant residues are disordered in the enzyme-statin complexes. If these residues were not flexible, they would sterically hinder statin binding.
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            Antioxidant capacity of 26 spice extracts and characterization of their phenolic constituents.

            Total equivalent antioxidant capacity (TEAC) and phenolic content of 26 common spice extracts from 12 botanical families were investigated. Qualitative and quantitative analyses of major phenolics in the spice extracts were systematically conducted by reversed-phase high-performance liquid chromatography (RP-HPLC). Many spices contained high levels of phenolics and demonstrated high antioxidant capacity. Wide variation in TEAC values (0.55-168.7 mmol/100 g) and total phenolic content (0.04-14.38 g of gallic acid equivalent/100 g) was observed. A highly positive linear relationship (R2= 0.95) obtained between TEAC values and total phenolic content showed that phenolic compounds in the tested spices contributed significantly to their antioxidant capacity. Major types of phenolic constituents identified in the spice extracts were phenolic acids, phenolic diterpenes, flavonoids, and volatile oils (e.g., aromatic compounds). Rosmarinic acid was the dominant phenolic compound in the six spices of the family Labiatae. Phenolic volatile oils were the principal active ingredients in most spices. The spices and related families with the highest antioxidant capacity were screened, e.g., clove in the Myrtaceae, cinnamon in the Lauraceae, oregano in the Labiatae, etc., representing potential sources of potent natural antioxidants for commercial exploitation. This study provides direct comparative data on antioxidant capacity and total and individual phenolics contents of the 26 spice extracts.
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              Statins: mechanism of action and effects.

              The beneficial effects of statins are the result of their capacity to reduce cholesterol biosyntesis, mainly in the liver, where they are selectively distributed, as well as to the modulation of lipid metabolism, derived from their effect of inhibition upon HMG-CoA reductase. Statins have antiatherosclerotic effects, that positively correlate with the percent decrease in LDL cholesterol. In addition, they can exert antiatherosclerotic effects independently of their hypolipidemic action. Because the mevalonate metabolism generates a series of isoprenoids vital for different cellular functions, from cholesterol synthesis to the control of cell growth and differentiation, HMG-CoA reductase inhibition has beneficial pleiotropic effects. Consequently, statins reduce significantly the incidence of coronary events, both in primary and secondary prevention, being the most efficient hypolipidemic compounds that have reduced the rate of mortality in coronary patients. Independent of their hypolipidemic properties, statins interfere with events involved in bone formation and impede tumor cell growth.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                09 April 2019
                April 2019
                09 April 2019
                : 5
                : 4
                : e01485
                Affiliations
                [1]Faculty of Pharmacy, Widya Mandala Catholic University Surabaya, Raya Kalisari Selatan 1, Pakuwon City, Surabaya 60112, Indonesia
                Author notes
                []Corresponding author. lanny.hartanti@ 123456gmail.com
                Article
                S2405-8440(18)36792-6 e01485
                10.1016/j.heliyon.2019.e01485
                6458466
                df938ed1-7db0-4301-9910-f0d26498227a
                © 2019 Published by Elsevier Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 18 October 2018
                : 16 March 2019
                : 3 April 2019
                Categories
                Article

                biochemistry,molecular biology,natural product chemistry

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