Potential of Naringin in Reducing Aorta Lesion Atherosclerosis in Hypercholesterolemia: A Systematic Review

Hypercholesterolemia is a condition that affects cholesterol levels because of the increase of LDL. Hypercholesterolemia is connected to atherosclerosis disease, which causes the blockage of blood flow. Naringin is a flavonoid primarily found in the citrus family and proved to have various benefits, one of which is antiatherogenic. The article searching was done in PubMed, Wiley Online Library, Cochrane, ProQuest, ScienceDirect, and Google Scholar databases. The final three studies about naringin supplementation in animals models are assessed. Naringin had an antiatherogenic effect and decreased the aorta lesion in atherosclerosis by several different mechanisms.

Influence of complex medical rehabilitation methods with the inclusion of nicotinic acid electrophoresis on the dynamics of metabolic status indicators in patients with myocardial infarction after percutaneous coronary interventions

A study of the metabolic status of 123myocardial infarction patients who underwent emergency percutaneous coronary intervention and were admitted to the inpatient stage of rehabilitation has been carried out. The examination of the patients revealed a high incidence of hyperglycemia, hyperuricemia, dyslipidemia and atherogenic cholesterol fraction. It has been found that the administration of a pathogenetically based therapeutic complex including physical therapy, manual massage, dry carbon dioxide baths, and 1% nicotinic acid electrophoresis has a significant antiatherogenic effect, and contributes to the correction of uric acid and glucose levels, and insulin resistance.

EFFECT OF DIHYDROQUERCETIN ON HYPERCHOLESTERINEMIA

The article is devoted to the study of the natural flavonoid dihydroquercetin (0.0125 g per 1 kg of animal weight in daily diet) effect on the development of experimental hypercholesterolemia in rabbits “Chinchilla”. Dihydroquercetin was obtained by extraction with ethyl acetate from crushed Siberian larch (Larix sibirica Ledeb., 1833) wood chips with several cycles of subsequent recrystallization from water (purity 90–92%). Hypercholesterolemia was induced by an atherogenic diet: 0.35 g of cholesterol in the diet per 1 kg of animal weight. The duration of the experiment was two months. It was shown that the introduction of dihydroquercetin into the daily diet of rabbits with alimentary hypercholesterolemia does not significantly affect the level of total cholesterol, as well as the concentration of its atherogenic fractions of LDL and VLDL in the blood. Nevertheless, it was found that, in comparison with the model of hypercholesterolemia, this natural compound contributes to the maintenance of an increased concentration of HDL cholesterol, which has an antiatherogenic effect. Accordingly, this reduces the value of the blood atherogenic coefficient, which reflects the degree of risk of atherosclerosis. In general, the data obtained predetermines the need for further research using various approaches to modeling hypercholesterolemia and atherosclerosis in experimental animals.

MODERN OPPORTUNITIES OF ATHEROSCLEROSIS PHARMACOTHERAPY: NEW DIRECTIONS

Despite the successful achievements in modern applied medicine and the application of hypolipidemic drugs into clinical practice for the past 50 years, the issue of prevention and treatment of atherosclerotic vascular disease (AVD) remains unsolved. Implementation of the theory of immunopathogenesis of atherosclerosis that was experimentally proved by modern studies allows the specialists to expand the possibilities of pharmacotherapy and pharmacoprevention for AVD. Thus, the aim of the present study was to analyze new directions in the development of anti-atherosclerotic drugs (AAD) with a pathogenetic activity that suppressed chronic autoimmune inflammation in the areas of atherosclerotic damage of vessels. In the course of the study, the search and analysis of the publications in the databases Web of Science, PubMed, and RSCI (Russian Science Citation Index) for the period of 2016-2018 were performed. According to the performed analysis, the most perspective molecular targets for AAD are pro-inflammatory and anti-inflammatory cytokines that develop a disbalance in patients with AVD. Thus, the drugs that are based on monoclonal antibodies to the tumor necrosis factor α (TNFα), and pro-inflammatory interleukins (1β, 17А), used for the treatment of rheumatoid arthritis and psoriasis, can be used for the treatment of AVD. Recombinant interleukins 6, 13, 19, and substances that suppress the expression of interferon regulatory factors will also exert an antiatherogenic effect. The studies on the modeling of the pathogenesis of AVD in inbred animals showed that other molecular targets for AAD could be enzymes involved in the lipid and immune cells metabolism. They include inositol requiring enzyme 1, proprotein convertase subtilisin/Kexin type 9, and the enzymes of paraoxonase family. Besides, the review includes the discussion of the successful application of drugs based on monoclonal antibodies to TNFα (infliximab), IL-17A (secukinumab) and IL-1β (canakinumab), as well as the drugs with antienzymatic activity (evolocumab and darapladib), in clinical practice for the treatment of AVD. The modern knowledge on molecular mechanisms of immunopathogenesis can give grounds for the development of drugs for pathogenetic pharmacotherapy and pharmacoprevention for the complications of AVD. The most effective solution would be the indication of drugs that affect the disbalance of cytokines and metabolic processes in the immune cells.

EFFECTS OF KARMIZOLE DERIVATE ON THE EXPRESSION OF APO A-I GENE IN THE RAT’S HYPERLIPIDEMIA MODEL

Azoles are the main antifungal drug class. The main mechanism of the azoles action is the intercalation in the sterol biosynthesis regulation. At the same time, the effect of the azole derivates on mammals is antiatherogenic. But there were no publication about connection between azole derivates effect on hyperlipidemia and expression of genes with antiatherogenic effects. In our work we used triton model of hyperlipodemia on rats to analyze the effect of carmizole injection on the expression of the main antiatherogenic genes and their regulators Apo A-I, HDL, LDL. We had four groups of rats: intact control group, triton control group, phenophibrate group and carmizole group. During a seven days we gave a per oral injections of carmizole for the carmizole group, phenophibrate (as a comparison drug) for phenophibrate group and 1% starch solution for triton control group. Liver tissue samples were used for RNA extraction and following RT-PCR (Real Time PCR) with primers for Apo A-I mRNA sequence. We have found, that Apo A-I mRNA level decreased in the triton control group to 17%, but restored up to 89% in the carmizole group. Carmizole derivate drug works like stimulator of Apo A-I gene expression. That increasing of the expression of antiatherogenic protein gene could me the base of the antiatherogenic effect of the carmizole derivate.