THE IMPACT OF HOP EXTRACT ACTIVE COMPONENTS ON METABOLIC DISTURBANCES IN ESTROGEN DEFICIENT FEMALE RATS WITH PREDIABETES

Abstract

A number of studies have shown a greater cardiovascular risk in women with type 2 diabetes compared to men. The latter may be due to more excessive manifestations of metabolic disorders in women, in particular postmenopausal, that develop even at the stage of prediabetes. Since the use of hormone replacement therapy in women after menopause had adverse results on the progression of cardiovascular events, an alternative method of reducing cardiovascular risk in postmenopausal women with prediabetes may be the use of phytoestrogens, which possess estrogen-like activity without negative side effects specific to exogenous estrogens. The aim of our study was to evaluate the effect of hop extract on metabolic disturbances in female rats with prediabetes under estrogen deficiency. Materials and methods. The study was conducted on three-month-old intact and ovariectomized Wistar rats with metabolic syndrome (MS) induced by high calorie diet (15% lard, 25% sucrose, 1% bile salts, 59% standard feed) for eight weeks. The test substances were administered intragastrically once per day in a dose of 20 μg/kg or 200 μg/kg b.w. in recalculation on 8-prenylnaringenin for hop extract and 200 μg/kg b.w. in recalculation on estradiol for the reference drug, from the fifth week after induction of metabolic syndrome. Results. It was revealed that administration of hop extract in a dose of 200 μg/kg, similar to estradiol, led to improvement in glucose tolerance and decrease in insulin resistance (p˂0.05) in estrogen deficient rats with MS. In contrast to estradiol, hop extract had no effect on the mass of uterus in ovariectomized animals. The use of hop extract only in the dose of 200 μg/kg, similar to estradiol, was accompanied by a significant decrease in body weight gain and visceral fat, as well as normalization of the total lipids content in serum of experimental animals (p˂0.05). It is of note, that hop extract resulted in decrease of hypertriglyceridemia (p˂0.05), but did not affect the level of total cholesterol, while estradiol reduced the concentration of total cholesterol (p˂0.05), and had no effect on the level of triglycerides. Hop extract in a dose of 200 μg/kg, as well as estradiol, led to a decrease in the intensity of lipid peroxidation induced by MS under estrogen deficiency, as evidenced by reduced concentration of conjugated dienes in serum (p˂0.05). At the same time, the total antioxidant activity of serum in these animals remained elevated compared to intact group. In rats with MS and hypoestrogenia, hop extract in the highest dose and estradiol resulted in complete normalization (p˂0.05) of the decreased level of NO stable metabolites in serum and the reduced activity of NO-synthase in heart. Conclusions. The revealed cardioprotective effect of hop extract that is realized due to the improved lipid profile and reduced insulin resistance, visceral obesity, oxidative stress and endothelial dysfunction in estrogen deficient female rats with MS indicates the prospects of its use for prevention and treatment of cardiovascular complications in postmenopausal women with prediabetes.