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Biochemical pharmacology

Biochemical pharmacology

IF: 5.3
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5-O-Methylvisammioside, a novel inhibitor of CNT2, improves hyperuricemia by inhibiting intestinal purine nucleoside absorption with a safe profile

Published:13 August 2025 DOI: 10.1016/j.bcp.2025.117236 PMID: 40816627
Suiqing Mai , Jiale Ke , Shiqin Lin , Rongrong Huang , Fengxin Zheng , He Jiao , Hong Wang , Shuqin Zhang , Mengying Mao , Qiuping Li , Zean Zhao , Jianxin Pang , Qun Zhang

Abstract

A high-purine diet is an important factor in the development of hyperuricemia (HUA), in which the intestinal tract is the main site of dietary purine absorption. Inhibition of intestinal concentrative nucleoside transporter 2 (CNT2) can inhibit dietary purine-induced elevation of serum uric acid (sUA) levels. However, there is a lack of research on CNT2 inhibitors for the treatment of HUA. By using high throughput virtual screening from an in-house natural product database, the natural active component 5-methylvisammioside (MeV) in Saposhnikovia divaricata (Turcz.) Schischk was predicted to be an effective CNT2 inhibitor with the highest docking score. In vitro,?MeV showed the strongest inhibitory activity against CNT2, with IC50 value of 11.22?±?2.18?μM. Moreover, MeV showed little or almost no inhibitory effect on other nucleoside transporters CNT3 and equilibrative nucleoside transporters (ENTs), as well as on uric acid (UA) transporter-related targets. In vivo, MeV significantly reduced sUA, inhibited adenosine uptake, and had an ameliorative effect on pathological changes in the liver, kidney, and intestinal tract. Moreover, MeV improved serum and intestinal indices related to inflammation and oxidative stress in mice, reduced intestinal permeability. Through our further study, we found that MeV inhibited the activation of reactive oxygen species (ROS) and NF-κB P65, reduced the production of the NOD-like receptor protein 3 (NLRP3) inflammasome, and improved intestinal injury in a high UA?environment. The study suggests that MeV is a potent CNT2 inhibitor for the treatment of?HUA and also protects intestinal function by inhibiting the ROS/NF-κB/NLRP3 pathway.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
1-beta-D-Arabinofuranosyluracil 3083-77-0 C9H12N2O6 500 suppliers $6.00-$2400.00
1-beta-D-Arabinofuranosyluracil 3083-77-0 C9H12N2O6 500 suppliers $6.00-$2400.00
1-beta-D-Arabinofuranosyluracil 3083-77-0 C9H12N2O6 500 suppliers $6.00-$2400.00
1-beta-D-Arabinofuranosyluracil 3083-77-0 C9H12N2O6 500 suppliers $6.00-$2400.00

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