Network Pharmacology-Based Exploration: Non-Targeted Metabolites of Lactobacillus-Fermented Chaenomeles speciosa (Sweet) Nakai, Smilax glabra Roxb. and Pueraria montana var. Lobata in Uric Acid Metabolism Intervention.

IF 4.5 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Biologics : Targets & Therapy Pub Date : 2026-02-24 eCollection Date: 2026-01-01 DOI:10.2147/BTT.S578004
Wei Tan, Zongjun Li
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引用次数: 0

Abstract

Background: Previous studies have demonstrated that numerous medicine and food homology (MFH) possess the potential to regulate purine metabolism disorders, promote uric acid excretion, and alleviate hyperuricemia symptoms. Examples include CS (Chaenomeles speciosa (Sweet) Nakai), SR (Smilax glabra Roxb.) and PL (Pueraria montana var. lobata).

Methods: Metabolomics was employed to analyze the compositional changes in medicinal and edible extracts before and after fermentation. Network pharmacology and molecular docking studies were further utilized to elucidate the interactions between these differential metabolites and the core targets of hyperuricemia. In vitro enzyme activity assays were conducted to confirm the therapeutic effects.

Results: A total of 283, 248, and 18 differential metabolites were identified in CS,SR and PL samples, respectively. Among these, 54 significantly upregulated differential metabolites were selected for screening. Based on these metabolites, 53 HUA-related targets were identified for CS, SR and PL. Functional enrichment analysis revealed their roles in inflammatory stress and uric acid production pathways, particularly the MAPK signaling pathway and purine metabolism regulated by XDH. Additionally, other targets in the purine metabolism pathway, such as ADA, PNP, AMPD3, and IMPDH2, were co-regulated. Enzyme activity assays indicate that fermented MFH more effectively inhibits XOD, thereby regulating the conversion of xanthine and hypoxanthine into uric acid. Molecular docking revealed two significantly upregulated compounds in CS; and five in PL; and four in SR. exhibit strong binding to XOD.

Conclusion: These findings provide theoretical support for FMFH as a potential effective component in preventing and treating hyperuricemia. Our research demonstrates that FMFH targets multiple pathways associated with hyperuricemia, offering a promising approach for preventing this condition.

基于网络药理学的探索:乳酸菌发酵木瓜(甜)Nakai, Smilax glabra Roxb的非靶向代谢物。葛根对尿酸代谢的干预作用。
背景:已有研究表明,许多药物和食物同源性(MFH)具有调节嘌呤代谢紊乱、促进尿酸排泄、缓解高尿酸血症症状的潜力。例如CS (Chaenomeles speciosa (Sweet) Nakai), SR (Smilax glabra Roxb.)和PL(葛根(Pueraria montana var. lobata))。方法:采用代谢组学方法,对发酵前后药用和食用提取物的成分变化进行分析。网络药理学和分子对接研究进一步阐明了这些差异代谢物与高尿酸血症核心靶点之间的相互作用。体外酶活性测定证实其治疗效果。结果:在CS、SR和PL样品中分别鉴定出283、248和18种差异代谢物。从中筛选出54个显著上调的差异代谢物进行筛选。基于这些代谢物,我们鉴定出了53个与CS、SR和PL相关的hua靶点。功能富集分析揭示了它们在炎症应激和尿酸生成途径中的作用,特别是在MAPK信号通路和XDH调节的嘌呤代谢中。此外,嘌呤代谢途径中的其他靶点,如ADA、PNP、AMPD3和IMPDH2也受到共同调控。酶活性分析表明,发酵的MFH更有效地抑制XOD,从而调节黄嘌呤和次黄嘌呤转化为尿酸。分子对接发现CS中有两个显著上调的化合物;5个在PL;sr中有4个与XOD结合较强。结论:本研究结果为FMFH作为防治高尿酸血症的潜在有效成分提供了理论支持。我们的研究表明,FMFH靶向与高尿酸血症相关的多种途径,为预防这种情况提供了一种有希望的方法。
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来源期刊
Biologics : Targets & Therapy
Biologics : Targets & Therapy MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
8.30
自引率
0.00%
发文量
22
审稿时长
16 weeks
文献相关原料
原料信息
原料厂家
1
GraphPad Prism
2
hypoxanthine
3
XOD assay kit
5
Water extract (10:1) of Chaenomeles speciosa, Smilax glabra, Pueraria montana var. lobata
6
xanthine oxidase
7
Ammonium formate
8
Formic acid
9
Acetonitrile
10
Methanol
11
Compound Discoverer
12
Q Exactive hybrid quadrupole-Orbitrap mass spectrometer
13
Vanquish UHPLC system
14
ACQUITY UPLC HSS T3 column
15
22
xanthine
69-89-6
¥17.00-¥15341.00
16
22
2-Chloro-L-phenylalanine
103616-89-3
¥17.00-¥16650.00
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