Division of Nephrology and National Clinical Research Center for Geriatrics, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, 610041, China.
State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, And Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
J Ethnopharmacol. 2021 Jan 10;264:113278. doi: 10.1016/j.jep.2020.113278. Epub 2020 Aug 22.
Liriodendron chinense (Hemsl.) Sarg, known as the Chinese tulip tree, has a long history of cultivation and utilization in many Asia countries, especially in China to use in traditional Chinese medicine for expelling "wind and dampness", a term corresponding to rheumatic fever and rheumatoid arthritis. Interestingly, the barks of Liriodendron chinense (Hemsl.) Sarg was also found in folk to treat gout. However, further experimental studies remained to confirm its uric acid-lowering effects.
The aim of the study was to evaluate the protective effect of ethanol extract of the barks of Liriodendron chinense (Hemsl.) Sarg (EELC) in a mouse model of hyperuricemic nephropathy (HN) and the involved mechanisms.
EELC at a respective dose of 250 mg/kg/d or 500 mg/kg/d were orally administered to HN mice induced by a mixture of adenine (160 mg/kg/d)/potassium oxonate (2.4 g/kg/d) for 21 days. At the end of the treatment, serum uric acid, kidney functions (serum creatinine, blood urea nitrogen and urine microalbumin), 24-h urine uric acid excretion, as well as kidney pathological changes were investigated by biochemical assay, histopathological score, immunofluorescence and histochemistry, RT-qPCR, and western blotting analysis.
Oral administration of EELC significantly lowered serum uric acid level at 500 mg/kg (185.75 ± 15.49 μmol/L of EELC vs. 238.28 ± 20.97 μmol/L of HN model, p < 0.01) in HN mice. EELC at 500 mg/kg also remarkably reduced the levels of serum creatinine (82.92 ± 7.86 μmol/L of EELC vs. 92.08 ± 6.13 μmol/L of HN model, p < 0.0001), blood urea nitrogen (21.50 ± 1.87 mmol/L of EELC vs. 29.40 ± 3.95 mmol/L of HN model, p < 0.001) and urine microalbumin (4.25 ± 0.40 mg/L of EELC vs. 5.95 ± 0.33 mg/L of HN model, p < 0.001) to improve renal function. It also attenuated renal fibrosis, especially the high-dose of EELC. Furthermore, EELC could inhibit the activation of NF-κB, ASK1/JNK/c-Jun, JAK2/STAT3 signaling pathways and reduce the release of pro-inflammatory cytokine TNF-α in the kidneys of HN mice. Additionally, EELC remarkably increased urine uric acid excretion of HN mice, which may be achieved by the upregulation of organic anion transporter 1 (OAT1), OAT3 and ATP-binding cassette subfamily G member 2 (ABCG2) proteins.
EELC alleviated the progression of HN by suppressing the activation of NF-κB, ASK1/JNK/c-Jun and JAK2/STAT3 signaling pathway, reducing the infiltration of inflammatory factors and uric acid accumulation in the kidney.
鹅掌楸（Liriodendron chinense（Hemsl.）Sarg），又称中国郁金香树，在中国和其他亚洲国家已有悠久的栽培和利用历史，用于传统中医药驱除“风邪和湿邪”，这一术语对应风湿热和类风湿关节炎。有趣的是，鹅掌楸的树皮也在民间用于治疗痛风。然而，仍需要进一步的实验研究来证实其降低尿酸的作用。
本研究旨在评估鹅掌楸树皮乙醇提取物（EELC）在高尿酸血症肾病（HN）小鼠模型中的保护作用及其相关机制。
采用腺嘌呤（160mg/kg/d）/氧嗪酸钾（2.4g/kg/d）混合物诱导 HN 小鼠，分别给予 EELC 250mg/kg/d 或 500mg/kg/d 剂量，连续 21 天进行口服给药。治疗结束时，通过生化测定、组织病理学评分、免疫荧光和组织化学、RT-qPCR 和 Western blot 分析，检测血清尿酸、肾功能（血清肌酐、血尿素氮和尿微量白蛋白）、24 小时尿尿酸排泄以及肾脏病理变化。
EELC 可显著降低 HN 小鼠血清尿酸水平（EELC 组 500mg/kg 时为 185.75±15.49μmol/L，HN 模型组为 238.28±20.97μmol/L，p<0.01）。EELC 还可显著降低 HN 小鼠的血清肌酐（EELC 组 500mg/kg 时为 82.92±7.86μmol/L，HN 模型组为 92.08±6.13μmol/L，p<0.0001）、血尿素氮（EELC 组 500mg/kg 时为 21.50±1.87mmol/L，HN 模型组为 29.40±3.95mmol/L，p<0.001）和尿微量白蛋白（EELC 组 500mg/kg 时为 4.25±0.40mg/L，HN 模型组为 5.95±0.33mg/L，p<0.001）水平，改善肾功能。它还可减轻肾脏纤维化，特别是高剂量的 EELC。此外，EELC 可抑制 HN 小鼠肾脏中 NF-κB、ASK1/JNK/c-Jun、JAK2/STAT3 信号通路的激活，并减少促炎细胞因子 TNF-α的释放。此外，EELC 还可显著增加 HN 小鼠的尿尿酸排泄，这可能是通过上调有机阴离子转运蛋白 1（OAT1）、OAT3 和 ABCG2 蛋白实现的。
EELC 通过抑制 NF-κB、ASK1/JNK/c-Jun 和 JAK2/STAT3 信号通路的激活，减少炎症因子的浸润和尿酸在肾脏中的积累，从而减轻 HN 的进展。
