Naringin enhances reverse cholesterol transport in high fat/low streptozocin induced diabetic rats

Abbreviations

• T2DM, type 2 diabetes mellitus;
• PON, paraoxonase;
• Hmgcr, hepatic 3-hydroxy-3-methylglutaryl-CoA reductase;
• Scarb1, scavenger receptor class B member 1;
• Ahr, aryl hydrocarbon receptor;
• Lipc, hepatic Lipase;
• Lcat, lecithin-cholesterol acyltransferase;
• VLDL, very low density lipoproteins;
• LDL, low density lipoproteins;
• HDL, high density lipoprotein;
• STZ, streptozotocin;
• HFD, high fat diet;
• DPP-IV, dipeptidyl peptidase-4;
• ELISA, enzyme linked immunosorbent assay;
• CPT, carnitine palmitoyl transferase;
• ACE, angiotensin converting enzyme;
• RT-PCR, reverse transcriptase polymerase chain reaction;
• GSP, gene specific primers

Keywords

• Diabetes mellitus;
• Gene expression;
• Lipid;
• Paraoxonase;
• Antioxidant

1. Introduction

Type 2 diabetes mellitus (T2DM) is the most prevalent form of diabetes and it is characterized by hyperglycemia associated with insulin resistance and impairment in insulin secretion with concomitant alteration in the intermediary metabolism of carbohydrate, protein and lipid [1,2]. The prevalence of T2DM has continued to be on the rise as a result of increase in obesity, which has been attributed to change in lifestyle and diet. Hence, the developing countries are expected to experience the greatest increase in the morbidity and mortality of this disease by the year 2025 [3].

T2DM is known to be associated with major complications like atherosclerotic coronary heart disease, cardiomyopathy, stroke and nephropathy. These complications are often responsible for increased mortality due to T2DM and they are associated with dyslipidemia and hypertension [2]. For example, atherosclerotic coronary heart disease is promoted by lipoprotein abnormalities which involve elevated very low density lipoproteins (VLDL) cholesterol and low high density lipoprotein (HDL) cholesterol [4]. Although the pathogenesis of atherosclerosis is complex, its development is dependent on the oxidation of LDL. This oxidation is prevented by paraoxonases, which are antioxidant protein component of lipoproteins, and are considered as better predictors of atherosclerotic risk than HDL in diabetes [5,6].

Although T2DM is a chronic disease, its management often involves control of both short-term and long-term diabetes-related problems [7]. Hence, the reduction of hyperglycemia and the risk of long-term complications is the target of any effective treatment regimen.

Although, there are a number of anti-diabetic pharmacological agents; they are however, limited by their unwanted side effects [8]. Thus, there has been a growing interest in nutraceuticals and functional food that can be useful in the management of T2DM and its associated complications.

Citrus is one of such functional foods that has been proposed to be beneficial in the management of diabetes mellitus and naringin is one of its active phytochemicals [9]. Naringin (PubChem CID: 442,428), a flavone glycoside, and aglycone of naringenin that gives grapefruit its bitter taste, has been reported for its antihyperglycemic, antioxidant and antihyperlipidemic properties [9,10]. For instance, Xulu and Oroma Owira [11] showed that naringin could ameliorate dyslipidemia in type I diabetic rats while Choi et al [10] further demonstrated the antioxidant effect of this flavonoid in rats fed with high cholesterol diet. Subsequently, the potential of naringin to improveT2DM in rats was demonstrated by Parmar et al. [12] using in silico, in vitro and in vivo inhibition of a biomarker of T2DM. Recently, Pari and Chandramohan [ 13] showed that the anti- T2DM property of naringin is due to the modulation of key carbohydrate metabolism enzymes in type 2 diabetic rat model.

However, more detailed studies are still needed to understand the mechanism by which naringin improves T2DM and prevents its associated complications. This present study therefore seeks to investigate the effects of naringin on a high fat fed/streptozotocin-induced T2DM rat model.

2. Materials and methods

2.1. Chemicals

Streptozotocin (STZ) was a product of Sigma-Aldrich (St. Loius, MO, USA) while Metformin was a product of Swipha Pharma, Lagos, Nigeria. Naringin was a product of Human Kang Biotechnology Company, Human Province, China. RNA later and RNA extraction spin column kits were products of Aidlab Biotechnologies Co. Ltd (Beijing, China) while TransGen Easy Script one-step RT-PCR kit was a product of TransGen Biotech Co. Ltd (Beijing, China). All other chemicals were products of Sigma-Aldrich (St. Loius, MO, USA).

2.2. Animals

Thirty male inbred albino rats weighing between 150 and 200 g were used for this study. The rats were housed in specific pathogen-free polypropylene cages under normal temperature (22 ± 2 °C) with 12-h light and dark cycle. The animals were allowed to acclimatize for three weeks before commencement of the experiment. The experiment was approved by the Covenant University Ethical Committee (CU/BIOSCRECU/BIO/2015/004) and carried out according to the guidelines of the committee.