Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, Jinghai District, Tianjin, 301617, China.
State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 10 Poyang Lake Road, Jinghai District, Tianjin, 301617, China.
J Nat Med. 2023 Sep;77(4):867-879. doi: 10.1007/s11418-023-01729-3. Epub 2023 Jul 12.
Hyperuricemia is an independent risk factor for chronic kidney disease. We have previously showed the uric-acid-lowering effect of Eurycoma longifolia Jack, yet the renal protective effect and mechanism of E. longifolia remain obscure. The mouse model of hyperuricemic nephropathy was induced by adenine combined with potassium oxonate in male C57BL/6 J mice. E. Longifolia alkaloid components could reduce the level of serum uric acid by regulating the expression of hepatic phosphoribosyl pyrophosphate synthase (PRPS), hypoxanthine-guanine phosphoribosyl transferase (HPRT), and renal urate transporter organic anion transporter 1 (OAT1) and ATP-binding box subfamily G member 2 (ABCG2) in HN mice. Additionally, E. Longifolia alkaloid components alleviated renal injury and function caused by hyperuricemia, which was characterized by improving renal histopathology, reducing urea nitrogen and creatinine levels. E. Longifolia alkaloid components treatment could reduce the secretion of pro-inflammatory factors by inhibiting the activation of NF-κB and NLRP3 inflammatory signaling pathways, including tumor necrosis factor α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-1 β (IL-1β), and regulated activated normal T cell expression and secretion proteins (RANTES). Meanwhile, E. longifolia alkaloid components improved renal fibrosis, inhibited the transformation of calcium-dependent cell adhesion molecule E (E-cadherin) to α-smooth muscle actin (α-SMA) transformation, and decreased collagen 1 expression in HN mice.
高尿酸血症是慢性肾脏病的独立危险因素。我们之前已经证明了长柄钩藤的降尿酸作用，但其肾保护作用和机制仍不清楚。通过腺嘌呤联合氧嗪酸钾诱导雄性 C57BL/6J 小鼠高尿酸血症肾病模型。长柄钩藤生物碱成分可通过调节肝脏磷酸核糖焦磷酸合酶（PRPS）、次黄嘌呤鸟嘌呤磷酸核糖转移酶（HPRT）和肾脏尿酸转运体有机阴离子转运体 1（OAT1）和 ATP 结合盒亚家族 G 成员 2（ABCG2）的表达来降低 HN 小鼠血清尿酸水平。此外，长柄钩藤生物碱成分可减轻高尿酸血症引起的肾损伤和功能障碍，其特征为改善肾组织病理学，降低尿素氮和肌酐水平。长柄钩藤生物碱成分治疗可通过抑制 NF-κB 和 NLRP3 炎症信号通路的激活来减少促炎因子的分泌，包括肿瘤坏死因子 α（TNF-α）、单核细胞趋化蛋白 1（MCP-1）、白细胞介素 1β（IL-1β）和调节激活正常 T 细胞表达和分泌蛋白（RANTES）。同时，长柄钩藤生物碱成分改善肾纤维化，抑制钙依赖性细胞黏附分子 E（E-cadherin）向α-平滑肌肌动蛋白（α-SMA）转化，减少 HN 小鼠胶原 1 表达。
