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Naringenin Ameliorates Hyperuricemia by Regulating Renal Uric Acid Excretion via the PI3K/AKT Signaling Pathway and Renal Inflammation through the NF-κB Signaling Pathway
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-12-16 , DOI: 10.1021/acs.jafc.2c01513 Bendong Yang 1 , Meiling Xin 1 , Shufei Liang 1 , Yuhong Huang 2 , Jingda Li 2 , Chao Wang 1 , Chao Liu 3 , Xinhua Song 1, 4 , Jinyue Sun 3, 5 , Wenlong Sun 1, 4
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2022-12-16 , DOI: 10.1021/acs.jafc.2c01513 Bendong Yang 1 , Meiling Xin 1 , Shufei Liang 1 , Yuhong Huang 2 , Jingda Li 2 , Chao Wang 1 , Chao Liu 3 , Xinhua Song 1, 4 , Jinyue Sun 3, 5 , Wenlong Sun 1, 4
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Hyperuricemia characterized by high serum levels of uric acid (UA, >6.8 mg/dL) is regarded as a common chronic metabolic disease. When used as a food supplement, naringenin might have various pharmacological activities, including antioxidant, free-radical-scavenging, and inflammation-suppressing activities. However, the effects of naringenin on hyperuricemia and renal inflammation and the underlying mechanisms remain to be elucidated. Here, we comprehensively examined the effects of naringenin on hyperuricemia and the attenuation of renal impairment. Mice were injected with 250 mg/kg of potassium oxonate (PO) and given 5% fructose water to induce hyperuricemia. The pharmacological effects of naringenin (10 and 50 mg/kg) and benzbromarone (positive control group, 20 mg/kg) on hyperuricemic mice were evaluated in vivo. The disordered expression of urate transporters in HK-2 cells was stimulated by 8 mg/dL UA, which was used to determine the mechanisms underlying the effects of naringenin in vitro. Naringenin markedly reduced the serum UA level in a dose-dependent manner and improved renal dysfunction. Moreover, the increased elimination of UA in urine showed that the effects of naringenin were associated with the regulation of renal excretion. Further examination indicated that naringenin reduced the expression of GLUT9 by inhibiting the PI3K/AKT signaling pathway and reinforced the expression of ABCG2 by increasing the abundance of PDZK1 in vivo and in vitro. Furthermore, sirius red staining and western blotting indicated that naringenin plays a protective role in renal injury by suppressing increases in the levels of pro-inflammatory cytokines, including IL-6 and TNF-α, which contribute to the inhibition of the TLR4/NF-κB signaling pathway in vivo and in vitro. Naringenin supplementation might be a potential therapeutic strategy to ameliorate hyperuricemia by promoting UA excretion in the kidney and attenuating the inflammatory response by decreasing the release of inflammatory cytokines. This study shows that naringenin could be used as a functional food or dietary supplement for hyperuricemia prevention and treatment.
中文翻译：
柚皮素通过 PI3K/AKT 信号通路调节肾尿酸排泄和通过 NF-κB 信号通路调节肾脏炎症改善高尿酸血症
以高血清尿酸水平（UA，>6.8 mg/dL）为特征的高尿酸血症被认为是一种常见的慢性代谢疾病。当用作食品补充剂时，柚皮素可能具有多种药理活性，包括抗氧化、清除自由基和抑制炎症的活性。然而，柚皮素对高尿酸血症和肾脏炎症的影响及其潜在机制仍有待阐明。在这里，我们全面检查了柚皮素对高尿酸血症和肾损伤减轻的影响。给小鼠注射 250 mg/kg 氧酸钾 (PO) 并给予 5% 果糖水以诱导高尿酸血症。体内评价柚皮素（10和50 mg/kg）和苯溴马隆（阳性对照组，20 mg/kg）对高尿酸血症小鼠的药理作用. 8 mg/dL UA 刺激 HK-2 细胞中尿酸盐转运蛋白的紊乱表达，用于确定柚皮素体外作用的潜在机制。柚皮素以剂量依赖的方式显着降低血清 UA 水平并改善肾功能障碍。此外，尿液中 UA 消除的增加表明柚皮素的作用与肾脏排泄的调节有关。进一步检测表明，柚皮素通过抑制 PI3K/AKT 信号通路降低 GLUT9 的表达，并通过增加 PDZK1在体内和体外的丰度来增强 ABCG2 的表达. 此外，天狼星红染色和蛋白质印迹表明，柚皮素通过抑制促炎细胞因子（包括 IL-6 和 TNF-α）水平的升高，在肾损伤中发挥保护作用，这有助于抑制 TLR4/NF- κB信号通路在体内和体外。柚皮素补充剂可能是一种潜在的治疗策略，可通过促进肾脏尿酸排泄和通过减少炎性细胞因子的释放来减轻炎症反应来改善高尿酸血症。本研究表明，柚皮素可作为功能性食品或膳食补充剂用于高尿酸血症的防治。
更新日期：2022-12-16
中文翻译：
柚皮素通过 PI3K/AKT 信号通路调节肾尿酸排泄和通过 NF-κB 信号通路调节肾脏炎症改善高尿酸血症
以高血清尿酸水平（UA，>6.8 mg/dL）为特征的高尿酸血症被认为是一种常见的慢性代谢疾病。当用作食品补充剂时，柚皮素可能具有多种药理活性，包括抗氧化、清除自由基和抑制炎症的活性。然而，柚皮素对高尿酸血症和肾脏炎症的影响及其潜在机制仍有待阐明。在这里，我们全面检查了柚皮素对高尿酸血症和肾损伤减轻的影响。给小鼠注射 250 mg/kg 氧酸钾 (PO) 并给予 5% 果糖水以诱导高尿酸血症。体内评价柚皮素（10和50 mg/kg）和苯溴马隆（阳性对照组，20 mg/kg）对高尿酸血症小鼠的药理作用. 8 mg/dL UA 刺激 HK-2 细胞中尿酸盐转运蛋白的紊乱表达，用于确定柚皮素体外作用的潜在机制。柚皮素以剂量依赖的方式显着降低血清 UA 水平并改善肾功能障碍。此外，尿液中 UA 消除的增加表明柚皮素的作用与肾脏排泄的调节有关。进一步检测表明，柚皮素通过抑制 PI3K/AKT 信号通路降低 GLUT9 的表达，并通过增加 PDZK1在体内和体外的丰度来增强 ABCG2 的表达. 此外，天狼星红染色和蛋白质印迹表明，柚皮素通过抑制促炎细胞因子（包括 IL-6 和 TNF-α）水平的升高，在肾损伤中发挥保护作用，这有助于抑制 TLR4/NF- κB信号通路在体内和体外。柚皮素补充剂可能是一种潜在的治疗策略，可通过促进肾脏尿酸排泄和通过减少炎性细胞因子的释放来减轻炎症反应来改善高尿酸血症。本研究表明，柚皮素可作为功能性食品或膳食补充剂用于高尿酸血症的防治。
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