Fig. 4

a A urate transport evaluation model to evaluate the effect of estradiol on urate transport in Caco-2 cells in vitro. b From the 12th hour after the addition of EB, urate transport by Caco-2 cells was significantly increased (P < 0.05). When treated with EB and elacridar, which is an ABCG2 inhibitor, the urate transport function of Caco-2 cells was partially weakened (P < 0.05). c A closed-loop intestinal circulation model to detect the level of intestinal urate excretion. The intestinal urate excretion of the HUA mouse group was significantly increased compared with that of the control mouse group (P < 0.05), and the intestinal urate excretion of HUA mice treated with EB was also significantly increased compared with that of the HUA mice (P < 0.05). d Analysis of ABCG2 protein expression by western blotting in intestinal tissues of each group showed that the intestinal ABCG2 expression of the HUA mice was higher than that in the control mice, and after EB intervention, the intestinal ABCG2 expression of the HUA mice was further increased. e Caco-2 cells were treated with different concentrations of EB, and 10^–4 mol/L EB was found to significantly upregulate ABCG2 mRNA levels without a dose-dependent effect. f Caco-2 cells were treated with LY294002 (50 μmol/L) in advance and then treated with EB (10^–4 mol/L) for 48 h. LY294002 partially blocked the effect of estradiol on the upregulation of ABCG2 mRNA expression (P < 0.05). g Estradiol did not change the total expression of Akt but regulated ABCG2 by activating p-Akt (S473) and p-Akt (T308), and this activation could also be blocked by LY294002