College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China; Department of Central Laboratory, Affiliated Quzhou Central Hospital, Zhejiang Chinese Medical University, Quzhou, 324000, China; Department of Pharmacy, Affiliated Quzhou Central Hospital, Zhejiang Chinese Medical University, Quzhou, 324000, China.
College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Biomed Pharmacother. 2019 Mar;111:162-168. doi: 10.1016/j.biopha.2018.12.050. Epub 2018 Dec 20.
Uric acid metabolic disorder is considered to be the main pathogenesis of uric acid nephropathy (UN). Smilax glabra Roxb. is a traditional Chinese herb which has been used in the treatment of gout, but the mechanism was unclear. In this study, we investigated the protective effects of the flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. (SGF) on uric acid nephropathy rats and its underlying mechanisms of promoting uric acid excretion. Sprague Dawley (SD) rats were induced by high purine diet (yeast pellets + adenine) for 5 weeks. Rats were orally treated with SGF or allopurinol daily. The biochemical parameters and enzymes in different treated rats were determined by commercial kits. Kidney pathology was visualized using optical microscopy and electron microscopy. Renal inflammatory factors were detected by ELISA. Renal fibrosis factors and uric acid transporters were analyzed by real time RT-PCR and western blot. The results showed that SGF significantly improved kidney function. Histopathologic examination revealed that urate-induced renal damage was markedly reversed by SGF. Meanwhile, SGF treatment was also found to significantly inhibit renal oxidative stress. SGF treatment obviously suppressed the inflammatory factors of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and the profibrotic factors of basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF-β) expression in UN rats. Moreover, SGF either significantly inhibited uric acid production or promoted uric acid excretion in UN rats. The mechanism of SGF promoting uric acid excretion was related to its increase of ATP-binding cassette transporter G2 (ABCG2), organic anion transporter 1 (OAT1), organic anion transporters 2 (OCT2) and organic cation/carnitine transporters 2 (OCTN2) expression. In conclusion, SGF could ameliorate renal oxidative stress and inflammation in UN rats through promoting uric acid excretion.
尿酸代谢紊乱被认为是尿酸肾病 (UN) 的主要发病机制。菝葜是一种传统的中药，用于治疗痛风，但作用机制尚不清楚。在这项研究中，我们研究了菝葜根茎富含黄酮的部分（SGF）对尿酸肾病大鼠的保护作用及其促进尿酸排泄的机制。SD 大鼠用高嘌呤饮食（酵母颗粒+腺嘌呤）诱导 5 周。大鼠每天口服 SGF 或别嘌呤醇。用商业试剂盒测定不同处理大鼠的生化参数和酶。用光学显微镜和电子显微镜观察肾脏病理。用 ELISA 检测肾炎症因子。用实时 RT-PCR 和 Western blot 分析肾纤维化因子和尿酸转运体。结果表明，SGF 显著改善了肾功能。组织病理学检查显示，SGF 明显逆转了尿酸诱导的肾损伤。同时，SGF 治疗还明显抑制了肾脏氧化应激。SGF 治疗明显抑制了 UN 大鼠白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)、白细胞介素-1β (IL-1β)、环氧化酶-2 (COX-2)等炎症因子和碱性成纤维细胞生长因子 (bFGF)、转化生长因子-β (TGF-β)等纤维化因子的表达。此外，SGF 显著抑制了 UN 大鼠尿酸的产生或促进了尿酸的排泄。SGF 促进尿酸排泄的机制与其增加三磷酸腺苷结合盒转运蛋白 G2 (ABCG2)、有机阴离子转运蛋白 1 (OAT1)、有机阴离子转运蛋白 2 (OCT2)和有机阳离子/肉碱转运蛋白 2 (OCTN2)的表达有关。综上所述，SGF 通过促进尿酸排泄，改善 UN 大鼠的肾氧化应激和炎症。
