Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People's Republic of China.
The First Affiliated Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, People's Republic of China.
Food Funct. 2021 Oct 4;12(19):9416-9431. doi: 10.1039/d1fo01830b.
seeds are considered as prospective nutraceuticals with a high content of unsaturated fatty acids (UFAs) which are mainly distributed in the oil. It is well-known that UFAs could exhibit urate-lowering potency and protect against renal injury, indicating that seed oil (SSO) may possess hypouricemic and nephroprotective effects. Consequently, the present work attempted to probe into the effects and mechanisms of SSO on potassium oxonate/hypoxanthine-induced hyperuricemia and associated renal injury. The results indicated that SSO treatment prominently inhibited the increase of serum uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) levels and hepatic xanthine oxidase (XOD) activity in hyperuricemia mice. Kidney indexes and histopathological lesions were also remarkably ameliorated. Additionally, SSO treatment improved the renal anti-oxidant status in hyperuricemia mice by significantly reversing the increase in ROS and MDA levels as well as the decline in SOD, CAT and GSH-Px activities. SSO dramatically downregulated the expression and secretion of pro-inflammatory factors involving MCP-1, IL-1β, IL-6, IL-18 and TNF-α elicited by hyperuricemia. Furthermore, after SSO treatment, increased protein expressions of GLUT9, URAT1 and OAT1 in the hyperuricemia mice were obviously reversed. SSO treatment enormously restored Nrf2 activation and subsequent translation of related anti-oxidative enzymes in the kidneys. TXNIP/NLRP3 inflammasome activation was also obviously suppressed by SSO. In conclusion, SSO exerted favorable hypouricemic effects owing to its dual functions of downregulating the XOD activity and modulating the expressions of renal urate transport-associated proteins, and it also could alleviate hyperuricemia-induced renal injury by restoring the Keap1-Nrf2 pathway and blocking the TXNIP/NLRP3 inflammasome activation.
种子被认为是具有高含量不饱和脂肪酸 (UFAs) 的有前途的营养保健品，这些脂肪酸主要分布在油中。众所周知，UFAs 具有降低尿酸的作用，并能保护肾脏免受损伤，这表明种子油 (SSO) 可能具有降尿酸和肾脏保护作用。因此，本研究试图探讨 SSO 对氧嗪酸钾/次黄嘌呤诱导的高尿酸血症及相关肾脏损伤的作用及机制。结果表明，SSO 治疗可显著抑制高尿酸血症小鼠血清尿酸 (UA)、肌酐 (CRE) 和尿素氮 (BUN) 水平及肝黄嘌呤氧化酶 (XOD) 活性的升高。肾脏指标和组织病理学损伤也得到明显改善。此外，SSO 治疗通过显著逆转 ROS 和 MDA 水平的升高以及 SOD、CAT 和 GSH-Px 活性的下降，改善了高尿酸血症小鼠的肾脏抗氧化状态。SSO 可显著下调由高尿酸血症引起的 MCP-1、IL-1β、IL-6、IL-18 和 TNF-α等促炎因子的表达和分泌。此外，SSO 治疗后，高尿酸血症小鼠中 GLUT9、URAT1 和 OAT1 的蛋白表达明显逆转。SSO 治疗可极大地恢复肾脏中 Nrf2 的激活及其相关抗氧化酶的翻译。SSO 还明显抑制了 TXNIP/NLRP3 炎性小体的激活。综上所述，SSO 通过下调 XOD 活性和调节肾脏尿酸转运相关蛋白的表达，发挥良好的降尿酸作用，通过恢复 Keap1-Nrf2 通路和阻断 TXNIP/NLRP3 炎性小体激活，缓解高尿酸血症引起的肾脏损伤。
