Balakina A S, Aksenov I V, Trusov N V, Guseva G V, Avrenyeva L I, Kravchenko L V, Tutelyan V A
Federal Research Centre of Nutrition, Biotechnology and Food Safety, Moscow.
Vopr Pitan. 2017;86(2):14-22. doi: 10.24411/0042-8833-2017-00029. Epub 2017 Feb 27.
The purpose of the study was to determine the effects of curcumin (CUR) and quercetin (QUER) on the expression of genes and activity of prototypical Nrf2/ARE- and AhR/ XRE-regulated enzymes. Investigation was carried out on male Wistar rats with initial body weight (230-235 g b.w.) that received for 14 days CUR (200 mg/kg b.w.) and QUER (200 mg/kg b.w.) separately or in combination within the standard semi-synthetic diet. The expression of genes and activity of Nrf2/ARE - regulated enzymes - heme oxygenase- 1(HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), AhR/XRE-regulated CYP1A1, CYP1A2 enzymes and the mRNA level of transcription factors Nrf2 and AhR were determined in rats liver. Also the expression of gene CYP3A1 and activity of CYP3A, UDP-glucuronosyltransferase, glutathione transferase were studied in rats liver. Along with this the total antioxidant activity (AOA), malondialdehyde and lipid hydroperoxides levels were determined in blood plasma and liver. The reduced and oxidized glutathione level, total and unsedimentable activity of lysosomal enzymes were investigated in rats' liver. QUER, especially in combination with CUR, increased the AOA of blood plasma and reduced the content of lipid hydroperoxides in it. CUR and QUER did not affect NQO1 activity, but the combined action caused an increase in the HO-1 activity without affecting the expression of the corresponding gene (Hmox1) and Nrf2 gene. CUR and, to a lesser extent QUER, had a strong inducing effect on CYP1A1, CYP1A2, CYP3A activity, but only the CYP1A1 activation was accompanied by the induction of CYP1A1 gene. The inducing effect of CUR and QUER on the activity of CYP450 enzymes greatly enhanced by their combined action. Membrane stabilizing action of CUR and QUER was also strongly expressed under its combined intake. Thus, we can conclude that CUR and QUER, especially in combination, contribute to the protective and adaptive capacity.
本研究的目的是确定姜黄素(CUR)和槲皮素(QUER)对典型的Nrf2/ARE-和AhR/XRE调控酶的基因表达和活性的影响。对初始体重为(230-235g体重)的雄性Wistar大鼠进行研究,这些大鼠在标准半合成饮食中分别或联合接受CUR(200mg/kg体重)和QUER(200mg/kg体重)14天。测定大鼠肝脏中Nrf2/ARE调控酶——血红素加氧酶-1(HO-1)、NAD(P)H:醌氧化还原酶1(NQO1)、AhR/XRE调控的CYP1A1、CYP1A2酶的基因表达和活性,以及转录因子Nrf2和AhR的mRNA水平。此外,还研究了大鼠肝脏中CYP3A1基因的表达以及CYP3A、UDP-葡萄糖醛酸基转移酶、谷胱甘肽转移酶的活性。与此同时,测定了血浆和肝脏中的总抗氧化活性(AOA)、丙二醛和脂质氢过氧化物水平。研究了大鼠肝脏中还原型和氧化型谷胱甘肽水平、溶酶体酶的总活性和不可沉降活性。QUER,尤其是与CUR联合使用时,可提高血浆的AOA并降低其中脂质氢过氧化物的含量。CUR和QUER不影响NQO1活性,但联合作用可导致HO-1活性增加,而不影响相应基因(Hmox1)和Nrf2基因的表达。CUR以及在较小程度上QUER对CYP1A1、CYP1A2、CYP3A活性有强烈的诱导作用,但只有CYP1A1的激活伴随着CYP1A1基因的诱导。CUR和QUER联合作用大大增强了它们对CYP450酶活性的诱导作用。CUR和QUER联合摄入时,其膜稳定作用也很明显。因此,我们可以得出结论,CUR和QUER,尤其是联合使用时,有助于提高保护和适应能力。