The Effect of Hydro-Alcoholic Extract of Fig on Paraoxonase1 Enzyme in a Rat Hyperlipidemia Model. An In-Silico and In-Vitro Study

Authors

DOI:

https://doi.org/10.22100/jkh.v18i2.2874

Abstract

Introduction: Paraoxonase-1 is a key enzyme against Low Density Lipoprotein (LDL) oxidation. Increased activity of this enzyme can lead to the prevention of atherosclerosis. This study investigated the effect of hydro-alcoholic extract of fig on the activity and gene expression of paraoxonase-1. Furthermore, the effect of the most effective compounds of fig on the function of this enzyme was investigated by simulation studies.

Methods: Forty male rats were studied in four groups (n=10). Hyperlipidemia groups were treated with 400 and 800 mg/kg of hydro-alcoholic extract of fig for 90 days. The serum lipid profile was measured by standardized assay. We investigated paraoxonase-1 gene expression and also paraoxonase1-arylesterase activity. Simulation and molecular dynamics studies of the most effective compounds of fig, including gallic acid and rutin, were performed using AutoDock v.4.2 and Gromacs 2018 software.

Results: The hydro-alcoholic extract of fig decreased the lipid profile of hyperlipidemia rats (P<0.001) but increased gene expression and paraoxonase-1 activity (P<0.05). According to the results of molecular dynamics studies, two compounds of rutin and gallic acid with a high tendency to bind to the enzyme paraoxonase-1 increase the rotational diffusion of the enzyme and correspondingly increase the possibility of activating the enzyme.

Conclusion: Not only did the hydro-alcoholic extract of fig reduces the lipid profile, but it also can considerably prevent atherosclerosis by activating the enzyme paraoxonase-1.

References

Jakobsen MU, Trolle E, Outzen M, Mejborn H, Grønberg MG, Lyndgaard CB, et al. Intake of dairy products and associations with major atherosclerotic cardiovascular diseases: a systematic review and meta-analysis of cohort studies. Scientific Reports 2021;14:1-28. doi: 10.1038/s41598-020-79708-x

Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation 2021;143:254-743. doi: 10.1161/CIR.0000000000000950

Ahmad F, Mitchell RD, Houben T, Palo A, Yadati T, Parnell AJ, et al. Cysteamine Decreases Low‐Density Lipoprotein Oxidation, Causes Regression of Atherosclerosis, and Improves Liver and Muscle Function in Low‐Density Lipoprotein Receptor-Deficient Mice. Journal of the American Heart Association 2021;10:e017524. doi: 10.1161/JAHA.120.017524

Zhang S, Li L, Chen W, Xu S, Feng X, Zhang L. Natural products: The role and mechanism in low‐density lipoprotein oxidation and atherosclerosis. Phytotherapy Research 2021;35:2945-67. doi: 10.1002/ptr.7002

Waqar AB, Koike T, Yu Y, Inoue T, Aoki T, Liu E, et al. High-fat diet without excess calories induces metabolic disorders and enhances atherosclerosis in rabbits. Atherosclerosis 2010;213:148-55. doi: 10.1016/j.atherosclerosis.2010.07.051

Yuan T, Yang T, Chen H, Fu D, Hu Y, Wang J, et al. New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis. Redox Biology 2019;20:247-60. doi: 10.1016/j.redox.2018.09.025

Kiriyama H, Kaneko H, Itoh H, Yoshida Y, Nakanishi K, Mizuno Y, et al. Effect of cigarette smoking on carotid artery atherosclerosis: a community-based cohort study. Heart and Vessels 2020;35:22-9. doi: 10.1007/s00380-019-01455-5

Litvinov D, Mahini H, Garelnabi M. Antioxidant and anti-inflammatory role of paraoxonase 1: implication in arteriosclerosis diseases. North American Journal of Medical Sciences 2021;4:523-11. doi: 10.4103/1947-2714.103310

Gong M, Garige M, Varatharajalu R, Marmillot P, Gottipatti C, Leckey LC, et al. Quercetin up-regulates paraoxonase 1 gene expression with concomitant protection against LDL oxidation. Biochemical and Biophysical Research Communications 2010;59:1372-8. doi: 10.1016/j.bbrc.2009.01.015

Mackness MI, Mackness B, Durrington PN, Fogelman AM, Berliner J, Lusis AJ, et al. Paraoxonase and coronary heart disease. Current Opinion in Lipidology 1998;9:319-24. doi: 10.1097/00041433-199808000-00006

Ayub A, Mackness MI, Arrol S, Mackness B, Patel J, Durrington PN. Serum paraoxonase after myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology 1999;19:330-5. doi: 10.1161/01.ATV.19.2.330

Mackness MI, Mackness B, Durrington PN. Paraoxonase and coronary heart disease. Atherosclerosis Supplements 2002;3:49-55. doi: 10.1016/S1567-5688(02)00046-6

Mackness B, Davies GK, Turkie W, Lee E, Roberts DH, Hill E, et al. Paraoxonase status in coronary heart disease: are activity and concentration more important than genotype? Arteriosclerosis, Thrombosis, and Vascular Biology 2001;21:1451-7. doi: 10.1161/hq0901.094247

Ghaffari T, Nouri M, Irannejad E, Rashidi M-R. Effect of vitamin E and selenium supplement on paraoxonase-1 activity, oxidized low density lipoprotein and antioxidant defense in diabetic rats. BioImpacts BI 2011;1:121.

Geng X, Liu H, Yuwen Q, Wang J, Zhang S, Zhang X, et al. Protective effects of zingerone on high cholesterol diet-induced atherosclerosis through lipid regulatory signaling pathway. Human & Experimental Toxicology 2021;40:1732-45. doi: 10.1177/09603271211006170

Fatemi A, Rasouli A, Asadi F. Effect of fig (Ficus carica) leaf extract on the secretion and content of cholesterol in Hepg2 cell. American Journal of Animal and Veterinary Sciences 2007;2:104-7. doi: 10.3844/ajavsp.2007.104.107

Hussain SZ, Naseer B, Qadri T, Fatima T, Bhat TA. Fig (Ficus Carica)-Morphology, Taxonomy, Composition and Health Benefits. Fruits Grown in Highland Regions of the Himalayas: Springer; 2021;16:77-90. doi: 10.1007/978-3-030-75502-7_6

Ali RJ, Baban RS, Ali SH. Evaluation of Lipid metabolizing enzymes: Paraxonase1 (PON1) and Lecithin Cholesterol acyltransferase (LCAT) activities in children with nephrotic syndrome. Baghdad Journal of Biochemistry and Applied Biological Sciences. 2021;2:47-58. doi: 10.47419/bjbabs.v2i01.38

Bakhtiari MK, Sharifiyazdi H, Nazifi S, Ghaemi M, Zarandi MH. Effects of citral on serum antioxidant status and liver genes expressions of paraoxonase 1 and nitric oxide synthase in a rat model of streptozotocin-induced diabetes mellitus. Iranian Journal of Veterinary Research. 2021;22:195.

Fatolahi H, Azarbayjani MA, Peeri M, Matinhomaei H. The effect of curcumin and exercise rehabilitation on liver paraoxonase-1 and NF-kβ gene expression in the rat induced by forced drinking of ethanol. Clinical and experimental hepatology. 2020;6:49. doi: 10.5114/ceh.2020.93057

Aboufarrag HT, Needs PW, Rimbach G, Kroon PA. The effects of anthocyanins and their microbial metabolites on the expression and enzyme activities of paraoxonase 1, an important marker of HDL function. Nutrients 2019;27:2887. doi: 10.3390/nu11122872

Parsaeyan N, Mozaffari-Khosravi H, Mozayan MR. Effect of pomegranate juice on paraoxonase enzyme activity in patients with type 2 diabetes. Journal of diabetes & metabolic disorders. 2012;11:1-4. doi: 10.1186/2251-6581-11-11

Demir Y, Türkeş C, Beydemir Ş. Molecular docking studies and inhibition properties of some antineoplastic agents against paraoxonase-I. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2020;20:887-96. doi: 10.2174/1871520620666200218110645

Alım Z, Kılıç D, Demir Y. Some indazoles reduced the activity of human serum paraoxonase 1, an antioxidant enzyme: in vitro inhibition and molecular modeling studies. Archives of physiology and biochemistry. 2019;125:387-95. doi: 10.1080/13813455.2018.1470646

Solomon A, Golubowicz S, Yablowicz Z, Grossman S, Bergman M, Gottlieb HE, et al. Antioxidant activities and anthocyanin content of fresh fruits of common fig (Ficus carica L.). Journal of Agricultural and Food Chemistry 2006;54:7717-23. doi: 10.1021/jf060497h

Veberic R, Colaric M, Stampar F. Phenolic acids and flavonoids of fig fruit (Ficus carica L.) in the northern Mediterranean region. Food Chemistry 2008;106:153-7. doi: 10.1016/j.foodchem.2007.05.061

Shaik AH, Shaik SR, Daddam JR, Ali D, Manoharadas S, Arafah MW, et al. Maslinic acid and gallic acid protective efficacy on lipids, lipoproteins and lipid metabolizing enzymes against isoproterenol administered cardiotoxicity: an in vivo and in silico molecular docking evidences. Journal of King Saud University-Science 2021;33:101230. doi: 10.1016/j.jksus.2020.101230

de Oliveira DA, Diniz SN, Pereira RM, Gonçalves ID, Rennó AL, Gorjão R, Vieira EG, da C. Ferreira AM, Okuyama CE. Effectiveness of a new rutin Cu (II) complex in the prevention of lipid peroxidation and hepatotoxicity in hypercholesterolemic rats. Journal of Food Biochemistry 2021;7:13999. doi: 10.1111/jfbc.13999

Rouhi-Broujeni H, Heidarian E, Darvishzadeh-Boroojeni P, Rafieian-Kopaei M, Gharipour M. Lipid lowering activity of Moringa pergerina seeds in rat: a comparison between the extract and atorvastatin. Research Journal of Biological Sciences 2013;8:150-4.

Zargari F, Tabaghchi Saeedy H. Effects of Vitamin C on Paraoxonase1 Arylesterase Activity in Rats Exposed to Arsenic. Iranian Journal of Toxicology. 2017;11:47-50. doi: 10.29252/arakmu.11.3.47

Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative CT method. Nature protocols. 2008;3:1101-8. doi: 10.1038/nprot.2008.7

Project E, Nachliel E, Gutman M. Force field‐dependant structural divergence revealed during long time simulations of Calbindin d9k. Journal of computational chemistry. 2010;31:1864-72. doi: 10.1002/jcc.21473

Downloads

Additional Files

Published

2023-11-26

Issue

Section

Original Article(s)

How to Cite

The Effect of Hydro-Alcoholic Extract of Fig on Paraoxonase1 Enzyme in a Rat Hyperlipidemia Model. An In-Silico and In-Vitro Study. (2023). Knowledge and Health in Basic Medical Sciences, 18(2), Page:60-68. https://doi.org/10.22100/jkh.v18i2.2874