Apigenin ameliorates hyperuricemic nephropathy by inhibiting URAT1 and GLUT9 and relieving renal fibrosis via the Wnt/β-catenin pathway.

Yongmei Li, Zean Zhao, Jian Luo, Yanqing Jiang, Lu Li, Yanyu Chen, Leqi Zhang, Qinghua Huang, Ying Cao, Pingzheng Zhou, Ting Wu, Jianxin Pang

Phytomedicine : international journal of phytotherapy and phytopharmacology 2021 Jul

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Hyperuricemia (HUA) is characterized by abnormal serum uric acid (UA) levels and demonstrated to be involved in renal injury leading to hyperuricemic nephropathy (HN). Apigenin (API), a flavonoid naturally present in tea, berries, fruits, and vegetables, exhibits various biological functions, such as antioxidant and anti-inflammatory activity. To investigate the effect of API treatment in HN and to reveal its underlying mechanisms. The mice with HN were induced by potassium oxonate intraperitoneally and orally administered for two weeks. The effects of API on renal function, inflammation, fibrosis, and uric acid (UA) metabolism in mice with HN were evaluated. The effects of API on urate transporters were further examined in vitro. The mice with HN exhibited abnormal renal urate excretion and renal dysfunction accompanied by increased renal inflammation and fibrosis. In contrast, API reduced the levels of serum UA, serum creatinine (CRE), blood urea nitrogen (BUN) and renal inflammatory factors in mice with HN. Besides, API ameliorated the renal fibrosis via Wnt/β-catenin pathway suppression. Furthermore, API potently promoted urinary UA excretion and inhibited renal urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in mice with HN. In vitro, API competitively inhibited URAT1 and GLUT9 in a dose-dependent manner, with IC50 values of 0.64 ± 0.14 μM and 2.63 ± 0.69 μM, respectively. API could effectively attenuate HN through co-inhibiting UA reabsorption and Wnt/β-catenin pathway, and thus it might be a potential therapy to HN. Copyright © 2021 Elsevier GmbH. All rights reserved.

Citation

Yongmei Li, Zean Zhao, Jian Luo, Yanqing Jiang, Lu Li, Yanyu Chen, Leqi Zhang, Qinghua Huang, Ying Cao, Pingzheng Zhou, Ting Wu, Jianxin Pang. Apigenin ameliorates hyperuricemic nephropathy by inhibiting URAT1 and GLUT9 and relieving renal fibrosis via the Wnt/β-catenin pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2021 Jul;87:153585