Yong Tianqiao, Chen Shaodan, Xie Yizhen, Shuai Ou, Li Xiangmin, Chen Diling, Su Jiyan, Jiao Chunwei, Liang Yalei
State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application and Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangzhou, China.
Guangdong Yuewei Edible Fungi Technology Co., Guangzhou, China.
Front Pharmacol. 2018 May 15;9:498. doi: 10.3389/fphar.2018.00498. eCollection 2018.
has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that of the normal control. Both AAE and AAW exhibited suppression effects on hepatic xanthine oxidase (XOD) activities and elevation effects on renal OAT1 (organic anion transporter 1). However, only little negative impact was observed on the inner organ functions. The molecular docking was used to screen our in-home compound database for , and four compounds including 2-formyl-3,5-dihydroxybenzyl acetate, 2,4-dihydroxy-6-methylbenzaldehyde, 2-(6-hydroxy-1H-indol-3-yl)acetamide, and 6-hydroxy-1H-indole-3-carbaldehyde (HHC) were identified as potential active compounds. Their inhibitory mechanism on XOD might be attributed to their localization in the tunnel for the entrance of substrates to XOD active site, preventing the entrance of the substrates. To confirm the activity of the screened compounds experimentally, HHC was selected due to its high ranking and availability. The assaying result suggested the significant inhibitory activity of HHC on XOD. Also, these compounds were predicted to carry good ADME (absorption, distribution, metabolism, and excretion) properties, thereby necessitating further investigation. The current results provided an insight into the hypouricemic effects of macrofungi and their bioactives, which might provide the significant theoretical foundation for identifying and designing novel hypouricemia compounds.
在传统中医中，它长期以来一直被用于促进利尿，与低尿酸血症密切相关。该化合物的乙醇提取物（AAE）和水提取物（AAW）可使高尿酸血症小鼠的血清尿酸水平（SUA）显著降低，接近正常对照组水平。AAE和AAW均对肝脏黄嘌呤氧化酶（XOD）活性有抑制作用，对肾脏有机阴离子转运体1（OAT1）有升高作用。然而，对内脏器官功能仅观察到很小的负面影响。通过分子对接在我们的内部化合物数据库中进行筛选，确定了四种化合物，包括2-甲酰基-3,5-二羟基苄基乙酸酯、2,4-二羟基-6-甲基苯甲醛、2-(6-羟基-1H-吲哚-3-基)乙酰胺和6-羟基-1H-吲哚-3-甲醛（HHC）为潜在活性化合物。它们对XOD的抑制机制可能归因于它们定位于XOD活性位点底物入口通道，阻止底物进入。为了通过实验证实筛选出的化合物的活性，由于HHC排名靠前且易于获得，故选择了HHC。测定结果表明HHC对XOD具有显著的抑制活性。此外，预测这些化合物具有良好的吸收、分布、代谢和排泄（ADME）特性，因此有必要进一步研究。目前的结果为大型真菌及其生物活性成分的降尿酸作用提供了见解，这可能为鉴定和设计新型降尿酸化合物提供重要的理论基础。
