ISSN - 0975-7058 Vol 10, Special Issue 1, 2018 ISSN - 0975-7058 INHIBITION OF 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE ACTIVITY BY EXTRACTS OF GARCINIA XANTHOCHYMUS MESOCARP AND TOTAL FLAVONOID ASSAY QUANTIFICATION OF THE MOST ACTIVE EXTRACT MEGAWATI, BERNA ELYA*, NURAINI PUSPITASARI Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, 16424, Indonesia. Email: berna.elya@farmasi.ui.ac.id Received: 20 June 2018, Revised and Accepted: 25 September 2018 and 31 October 2018 ABSTRACT Objective: This study aims to determine the inhibitory activity of Garcinia xanthochymus mesocarp extracts against 3-hydroxy-3-methylglutaryl -coenzyme A (HMG-CoA) reductase. Methods: G. xanthochymus mesocarp was macerated sequentially using n-hexane, ethyl acetate, and methanol. Phytochemical screening and quantification of total flavonoids were performed on the most active extract. Results: Based on the tests, n-hexane, ethyl acetate, and methanol extracts had inhibitory activities of 12.30±1.098%, 55.63±10.584%, and 44.01±1.053%, respectively. The results showed that the ethyl acetate is the most active extract, containing flavonoid, terpenoid, glycoside, and anthraquinone compounds. The amount of total flavonoid contained in ethyl acetate extract was 1.61% or 16.114 mg QE/g toward quercetin. Conclusion: The n-hexane, ethyl acetate, and methanol extracts of G. xanthochymus have inhibitory actions against HMG-CoA reductase activity in vitro. Further research is still needed to strengthen this finding. Keywords: Garcinia xanthochymus mesocarp, Total flavonoid, 3-Hydroxy-3-methylglutaryl-coenzyme A reductase, Sequential maceration, Phytochemical screening. INTRODUCTION Cholesterol is an amphiphilic lipid that is an essential structural component of the plasma membrane and the outer layer of plasma lipoproteins. It is synthesized in many tissues, is catalyzed by acetyl coenzyme A (acetyl-CoA), and is the precursor of all other steroids in the body, including corticosteroids, sex hormones, bile acids, and Vitamin D [1]. Hypercholesterolemia is characterized by elevated levels of low-density lipoprotein (LDL) or total cholesterol and low levels of high-density lipoprotein [2]. Hypercholesterolemia is a risk factor for non-infectious cardiovascular and metabolic diseases, such as atherosclerosis, metabolic syndrome, coronary heart disease, and stroke [3]. The drugs commonly used for the treatment of hypercholesterolemia include statins (simvastatin, atorvastatin, lovastatin, fluvastatin, rosuvastatin, and pravastatin), bile acid sequestrants (colestipol, colesevelam, and cholestyramine), nicotinic acid (niacin), and acid derivative fibrates: Peroxisome proliferator-activated receptors-α activators (clofibrate, gemfibrozil, fenofibrate, bezafibrate, and cyprofibrate), ezetimib, and fish oil supplements [4]. First-line therapy for hypercholesterolemia commonly uses statin drugs that inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, an enzyme that catalyzes the biosynthesis of cholesterol [1]. Plants of the Garcinia genus belong to the Clusiaceae or Guttiferae family. Currently, there are approximately 250 identified Garcinia species [5]. Garcinia xanthochymus is found mainly in Indonesia, especially in areas at altitudes of 1–500 m above sea level [6]. Some Garcinia species, such as Garcinia atroviridis and Garcinia cambogia, contain hydroxycitric acid (HCA), which has a hypolipidemic effect by decreasing lipogenesis and promoting glycogen progression, thereby suppressing the appetite [5]. HCA is a competitive inhibitor of adenosine 5‘-triphosphate citrate lyase, an enzyme that catalyzes the extramitochondrial conversion of citrate to oxaloacetate and acetyl-CoA. Reduced availability of acetyl- CoA decreases the biosynthesis of fatty acids and cholesterol as well as lipogenesis [7]. According to Darwati and Supriyatna, the ethanol extract of G. xanthochymus bark can lower LDL levels in white mouse (Mus musculus) blood with extract levels below 100 mg/bb [8]. Based on chemotaxonomic considerations, G. xanthochymus is thought to contain HCA, as other Garcinia species can have similar effects. G. xanthochymus contains quercetin [9], which is one of the most effective flavonoids to prevent LDL oxidation, as compared with other flavonoids such as myricetin, kaempferol, and morin [10]. Other compounds contained in G. xanthochymus include the biflavonoids morelloflavone and fukugetin [11]. According to Tuansulong et al., isolated morelloflavone compounds from Garcinia dulcis leaves can inhibit HMG-CoA reductase activity, which has a role in cholesterol biosynthesis, with an inhibition constant of 80.87±0.06 μM against HMG-CoA and 103±0.07 μM against NADPH [12]. To gain knowledge of herbal plants in Indonesia, especially G. xanthochymus, researchers would like to know the ability of G. xanthochymus fruit extract to inhibit the activity of HMG-CoA reductase, an enzyme that has a role in cholesterol biosynthesis. METHODS Extraction G. xanthochymus fruits were collected and wet-sorted washed with water, and dried. The fruits were cleaned, peeled, and cut into thin slices to speed up the drying process. The fruits were dried in an oven. The dried simplisia was then dry-sorted and grinded. Extraction was performed on simplisia powder by maceration using a multilevel extraction Research Article © 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ijap.2018.v10s1.59 The 2 nd Physics and Technologies in Medicine and Dentistry Symposium (PTMDS), Universitas Indonesia. Depok, Indonesia