Anti-HMG-CoA reductase and antioxidant activities of Sacha inchi (Plukenetia volubilis L.) nutshell extract
Article Sidebar
Main Article Content
Abstract
Background: Hypercholesterolemia is one of the major risks of cardiovascular diseases (CVDs). Hypercholesterolemia and oxidative stress are involved in the pathogenesis of atherosclerosis. Thailand has high percentage of unawareness of hypercholesterolemia, with low percentage of treatment and control. HMG-CoA reductase is a rate limiting step enzyme in cholesterol biosynthesis. Synthetic drugs such as statin are normally used to lower cholesterol level, however it causes adverse effects on the liver and muscle. Thus, HMG-CoA reductase inhibitors of plant origin are needed. Plukenetia volubilis Linneo, commonly known as Sacha inchi or inca peanut is a potential oilseed crop. The seeds of this plant are rich in omega-3 fatty acid. Some studies have shown that consuming Sacha inchi could reduce blood cholesterol. However, the exact mechanism of their lipid lowering activity is still unknown.
Objectives: This study aimed to investigate the anti-HMG-CoA reductase, anti-cholesterol esterase and antioxidant activities of different parts of Sacha inchi extracts.
Materials and methods: Hot water extracts of 3 different parts of Sacha inchi (nutshell, baby nut and leaf) and Sacha inchi nut oil were evaluated the anti-HMG-CoA reductase and antioxidant activities. HMG-CoA reductase inhibitory activity was determined spectrophotometrically by NADPH oxidation, using HMG-CoA as a substrate. HMG-CoA reductase inhibitory mechanism was also analyzed by using Lineweaver-Burk plot. Antioxidant activity was determined by ABTS and DPPH radical scavenging assay. Total phenolic content was also measured by Folin-Ciocalteu reagent. Moreover, cholesterol esterase inhibition assay was also performed.
Results: Sacha inchi nutshell extract revealed the highest anti-HMG-CoA reductase activities at about 99% at concentration of 250 µg/mL, with uncompetitive inhibition in Lineweaver-Burk plot analysis. It also showed the highest cholesterol esterase inhibitory activity around 38% at concentration of 125 µg/mL. Moreover, Sacha inchi nutshell extract also showed the highest antioxidant activity by both ABTS and DPPH assay. Antioxidant activity was correlated to total phenolic content.
Conclusion: The experimental data suggested that Sacha inchi nutshell extract is a source of antioxidant compound and may lower cholesterol level by inhibiting HMG-CoA reductase and cholesterol esterase enzymes. Investigation in an in vivo model could further confirm the potential use of Sacha inchi nutshell extract as a supplement for treatment of hypercholesterolemia.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Personal views expressed by the contributors in their articles are not necessarily those of the Journal of Associated Medical Sciences, Faculty of Associated Medical Sciences, Chiang Mai University.
References
Reddy KS, Yusuff S. Emerging epidemic of cardiovascular disease in developing countries. Circulation 1998; 97: 596-601.
Ohira T, Iso H. Cardiovascular disease epidemiology in Asia: an overview. Circ J 2013; 77(7): 1646-52.
Kilkenny MF, Dunstan L, Busingye D, Purvis T, Reyneke M, Orgill M, et al. Knowledge of risk factors for diabetes or cardiovascular disease (CVD) is poor among individuals with risk factors for CVD. PloS one 2017; 12(2): e0172941-e.
Maliszewska K, Adamska-Patruno E, Kretowski A. The interplay between muscle mass decline, obesity, and type 2 diabetes. Pol Arch Intern Med 2019; 129(11): 809-816. doi: 10.20452/pamw.15025.
Combes A, Franchineau G. Fine particle environmental pollution and cardiovascular diseases. Metabolism 2019; 100S: 153944. doi: 10.1016/j.metabol.2019.07.008.
Bellosta S, Corsini A. Statin drug interactions and related adverse reactions: an update. Expert Opin Drug Saf 2018; 17(1): 25-37.
Salvamani S, Gunasekaran B, Shaharuddin NA, Ahmad SA, Shukor MY. Antiartherosclerotic effects of plant flavonoids. Biomed Res Int 2014; 2014: 480258. doi: 10.1155/2014/480258.
Krause BR, Sliskovic DR, Anderson M, Homan R. Lipid-lowering effects of WAY-121,898, an inhibitor of pancreatic cholesteryl ester hydrolase. Lipids 1998; 33: 489-98.
Bailey JM, Gallo LL, Gillespie J. Inhibition of dietary cholesterol ester absorption by 3-BCP, a suicide inhibitor of cholesterol-esterase. Biochem Soc Trans 1995; 23: 408S.
Jeon SM, Kim HS, Lee TG, Ryu SH, Suh PG, Byun SJ, et al. Lower absorption of cholesteryl oleate in rats supplemented with Areca catechu L. extract. Ann Nutr Metab 2000; 44: 170–6.
Wang S, Zhu F, Kakuda Y. Sacha inchi (Plukenetia volubilis L.): Nutritional composition, biological activity, and uses. Food Chem 2018; 265: 316-28.
Vicente J, de Carvalho MG, Garcia-Rojas EE. Fatty acids profile of Sacha Inchi oil and blends by 1H NMR and GC-FID. Food Chem 2015; 181: 215-21.
Chirinos R, Zuloeta G, Pedreschi R, Mignolet E, Larondelle Y, Campos D. Sacha inchi (Plukenetia volubilis): a seed source of polyunsaturated fatty acids, tocopherols, phytosterols, phenolic compounds and antioxidant capacity. Food Chem 2013; 141(3): 1732-9.
Garmendia F, Pando R, Ronceros G. Effect of sacha inchi oil (Plukenetia volúbilis L.) on the lipid profile of patients with hyperlipoproteinemia. Rev Peru Med Exp Salud Publica 2011; 28(4): 628-32.
Bueno-Borges LB, Sartim MA, Gil CC, Sampaio SV, Rodrigues PHV, Regitano-d'Arce MAB. Sacha inchi seeds from sub-tropical cultivation: effects of roasting on antinutrients, antioxidant capacity and oxidative stability. J Food Sci Technol 2018; 55(10): 4159-66.
Tian W, Xiao N, Yang Y, Xiao J, Zeng R, Xie L, et al. Structure, antioxidant and immunomodulatory activity of a polysaccharide extracted from Sacha inchi seeds. Int J Biol Macromol 2020; 162:116-126.
Dewanto V, Wu X, Adom KK, Liu RH. Thermal processing enhances the nutritional value of tomatoes by increasing total antioxidant activity. J Agric Food Chem 2002; 50(10): 3010-4.
Kokina M, Salević A, Kalušević A, Lević S, Pantić M, Pljevljakušić D, et al. Characterization, antioxidant and antibacterial activity of essential Oils and their encapsulation into biodegradable material followed by freeze drying. Food Technol Biotechnol 2019; 57(2): 282-9.
Hajlaoui H, Arraouadi S, Mighri H, Chaaibia M, Gharsallah N, Ros G, et al. Phytochemical constituents and antioxidant activity of Oudneya Africana L. leaves extracts: evaluation effects on fatty acids and proteins oxidation of beef burger during refrigerated storage. Antioxidants (Basel) 2019; 8(10): 442. doi: 10.3390/antiox8100442.
Asmaa BH, Ream N. In vitro screening of the pancreatic cholesterol esterase inhibitory activity of some medicinal plants grown in Syria. Int J Pharmacognosy and Phytochem Res 2016; 8(8); 1432-36.
Lopes RHO, Macorini LFB, Antunes KA, Espindola PPT, Alfredo TM, Rocha PS, et al. Antioxidant and hypolipidemic activity of the hydroethanolic extract of Curatella americana L. leaves. Oxid Med Cell Longev 2016; 2016: 9681425.
Sirtori CR. The pharmacology of statins. Pharmacol Res 2014; 88: 3-11.
Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol 2016; 67(20): 2395-2410.
Gunasekaran B, Shukor MY. HMG-CoA reductase as target for drug development. Methods Mol Biol 2020; 2089: 245-250.
Gholamhoseinian A, Shahouzehi B, F S-F. Inhibitory activity of some plant methanol extracts on 3-hydroxy-3-methylglutaryl coenzyme a reductase. Int J Pharmacol 2010; 6(5): 705-11.
Baskaran G, Salvamani S, Ahmad SA, Shaharuddin NA, Pattiram PD, Shukor MY. HMG-CoA reductase inhibitory activity and phytocomponent investigation of Basella alba leaf extract as a treatment for hypercholesterolemia. Drug Des Devel Ther 2015; 9: 509-17.
Salvamani S, Gunasekaran B, Shukor MY, Shaharuddin NA, Sabullah MK, Ahmad SA. Anti-HMG-CoA reductase, antioxidant, and anti-Inflammatory activities of Amaranthus viridis leaf extract as a potential treatment for hypercholesterolemia. Evid Based Complement Alternat Med 2016; 2016: 8090841. doi: 10.1155/2016/8090841.
Iqbal D, Khan MS, Khan MS, Ahmad S, Hussain MS, Ali M. Bioactivity guided fractionation and hypolipidemic property of a novel HMG-CoA reductase inhibitor from Ficus virens Ait. Lipids Health Dis 2015; 14: 15. doi: 10.1186/s12944-015-0013-6.
da Costa RF, Freire VN, Bezerra EM, Cavada BS, Caetano EW, de Lima Filho JL, et al. Explaining statin inhibition effectiveness of HMG-CoA reductase by quantum biochemistry computations. Phys Chem Chem Phys 2012; 14(4): 1389-98.
Kato E, Tsuji H, Kawabata J. Selective purification of intestinal maltase complex by affinity chromatography employing an uncompetitive inhibitor as the ligand. Tetrahedron 2015; 71(9): 1419–24.
Gonzales GF, Gonzales C. A randomized, double-blind placebo-controlled study on acceptability, safety and efficacy of oral administration of sacha inchi oil (Plukenetia volubilis L.) in adult human subjects. Food Chem Toxicol 2014; 65: 168–76.