Evidence map›Paper›PMID 40790034›Full record

ArticleNature communications2025

Discovery of multi-target anti-gout agents from Eurycoma longifolia Jack through phenotypic screening and structural optimization.

Zhijiao Zhang, Xiaoyu Shi, Ting Wu, Zhuhan He, Ruipeng Liang, Wenjie Ye, Zhenkun Wu, Hui Liao, Fengxin Zheng, Qian Yang and 16 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Zhijiao Zhang *State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Xiaoyu Shi *State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Ting Wu *NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China.
Zhuhan HeDepartment of Pharmacology; Shandong University School of Medicine, Jinan, P. R. China.
Ruipeng LiangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Wenjie YeNMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China.
Zhenkun WuNMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China.
Hui LiaoNMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China.
Fengxin ZhengNMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China.
Qian YangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Zean ZhaoNMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China.
Yongjun ChenNMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China.
Zhen GaoState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Shuo WangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Mei WangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Zhenqian WangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Danhui QiState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Mingyu YangState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Shujing XuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Youzhao WangDepartment of Pharmacology; Shandong University School of Medicine, Jinan, P. R. China.
Tong ZhaoState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China.
Javier EgeaUnidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.ORCID http://orcid.org/0000-0003-4704-3019
Xinyong LiuState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China. xinyongl@sdu.edu.cn.ORCID http://orcid.org/0000-0002-7302-2214
Jianxin PangNMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening & Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China. pjx@smu.edu.cn.ORCID http://orcid.org/0000-0002-0053-2723
Fan YiDepartment of Pharmacology; Shandong University School of Medicine, Jinan, P. R. China. fanyi@sdu.edu.cn.ORCID http://orcid.org/0000-0001-8634-9788
Peng ZhanState Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, P. R. China. zhanpeng1982@sdu.edu.cn.ORCID http://orcid.org/0000-0002-9675-6026

Funding

National Natural Science Foundation of China (National Science Foundation of China) No.82373921National Natural Science Foundation of China (National Science Foundation of China) No.82473769National Natural Science Foundation of China (National Science Foundation of China) No.T2321004
6 · The paper itself

Abstract

Developing anti-gout medications that simultaneously reduce uric acid and exert anti-inflammatory effects represents a critical breakthrough for managing gout progression. Natural products with polypharmacological properties offer promising leads for drug discovery. In this study, β-carboline-1-propionic acid, a bioactive constituent of Eurycoma longifolia Jack, served as the starting point for drug design. Guided by a dual-target pharmacophore model, we design and synthesize 64 derivatives. Through systematic screening, 32 emerges as a drug candidate, demonstrating potent uric acid-lowering activity in male hyperuricemia mouse models (efficacy comparable to febuxostat and superior to lesinurad and benzbromarone) by inhibiting key urate transporters. In a male rat model of acute gouty arthritis, 32 mitigates NOD-like receptor protein 3 inflammasome-mediated inflammation. Notably, 32 exhibits enhanced safety compared to control drugs. This study exemplifies a natural product-inspired, dual-mechanism drug discovery approach, showcasing the potential of a rational polypharmacology and thus offering therapeutic opportunities for gout management.

Indexed as

EurycomaGoutGout SuppressantsAnimalsArthritis, GoutyCarbolinesDisease Models, AnimalDrug DiscoveryDrug Evaluation, PreclinicalHumansHyperuricemiaMaleMicePlant ExtractsRatsRats, Sprague-DawleyCarbolinesGout SuppressantsPlant ExtractsUric Acid

Identifiers

PMID40790034
PMCPMC12340016

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.