Anti-hyperuricemic and anti-inflammatory actions of vaticaffinol isolated from Dipterocarpus alatus in hyperuricemic mice
Anti-hyperuricemic and anti-inflammatory actions of vaticaffinol isolated from Dipterocarpus alatus in hyperuricemic mice
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DOI：
10.1016/s1875-5364(17)30053-5
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发表时间：
2017-05-01
影响因子：
4.6
通讯作者：
Kong Ling-Dong
中科院分区：
文献类型：
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作者：
Chen Yu-Sheng;Chen Chao-Jun;Kong Ling-Dong
本研究旨在研究从芦竹乙醇提取物中分离的白藜芦醇四聚体异咖啡因对草酸盐诱导的高尿酸血症小鼠的抗高尿酸血症和抗炎作用及其可能的机制。在给予250 mg.kg（-1）氧酸钾1 h后，高尿酸血症小鼠每天一次灌胃20、40和60 mg.kg（-1）的异咖啡因，连续7天。咖啡因能显著降低高尿酸血症小鼠血清尿酸水平，改善肾功能。抑制高尿酸血症小鼠肝脏黄嘌呤脱氢酶（XDH）和黄嘌呤氧化酶（XOD）活性，调节肾脏尿酸转运蛋白1 （URAT1）、葡萄糖转运蛋白9 （GLUT9）、有机阴离子转运蛋白1 （OAT1）、有机阳离子转运蛋白1 （OCT1）、OCT2、有机阳离子/肉碱转运蛋白1 （OCTN1）和OCTN2 mRNA和蛋白水平。此外，在该动物模型中，变咖啡因显著下调nod样受体3 （NLRP3）、凋亡相关斑点样（ASC）和Caspase-1的肾脏蛋白水平，导致白细胞介素(IL)-1 β、IL-18、IL-6和肿瘤坏死因子- α (tnf - α)水平降低。此外，HPLC和LC-MS分析清楚地证实了粗提取物中存在异丙酚。这些结果表明，异咖啡因可能有助于预防和治疗高尿酸血症伴肾炎症。
The present study was designed to examine the anti-hyperuricemic and anti-inflammatory effects and possible mechanisms of vaticaffinol, a resveratrol tetramer isolated from ethanol extracts of Dipterocarpus alatus, in oxonate-induced hyperuricemic mice. At 1 h after 250 mg.kg(-1) potassium oxonate was given, vaticaffinol at 20, 40, and 60 mg.kg(-1) was intragastrically administered to hyperuricemic mice once daily for seven consecutive days. Vaticaffinol significantly decreased serum uric acid levels and improved kidney function in hyperuricemic mice. It inhibited hepatic activity of xanthine dehydrogenase (XDH) and xanthine oxidase (XOD), regulated renal mRNA and protein levels of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporter 1 (OAT1), organic cation transporter 1 (OCT1), OCT2, organic cation/carnitine transporter 1 (OCTN1), and OCTN2 in hyperuricemic mice. Moreover, vaticaffinol markedly down-regulated renal protein levels of NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), and Caspase-1, resulting in the reduction of interleukin (IL)-1 beta, IL-18, IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels in this animal model. Additionally, HPLC and LC-MS analyses clearly testified the presence of vaticaffinol in the crude extract. These results suggest that vaticaffinol may be useful for the prevention and treatment of hyperuricemia with kidney inflammation.