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石香薷提取物通过调节小鼠尿酸代谢及减轻肾脏炎症和纤维化来缓解高尿酸血症。

Moslae Herba extract alleviates hyperuricemia by regulating uric acid metabolism and relieving renal inflammation and fibrosis in mice.

作者信息

Guo Jian, Liu Huanhuan, Jin Tong, Jia Jinhui, Zhu Wenxiu, Xia Xiaodong

机构信息

State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian, Liaoning 116034, PR China.

Department of Food Safety, College of Food Science and Engineering, Northwest A&F University, Xianyang, Shanxi 712100, PR China.

出版信息

Phytomedicine. 2025 Sep;145:156974. doi: 10.1016/j.phymed.2025.156974. Epub 2025 Jun 11.

DOI:10.1016/j.phymed.2025.156974
PMID:40541125
Abstract

BACKGROUND

Hyperuricemia (HUA) is a metabolic disease caused by uric acid metabolism disorder and is prevalent worldwide. Moslae Herba is a traditional herbal medicine known for its anti-inflammatory, antioxidant, and diuretic effects.

PURPOSE

This study aimed to investigate the effects and potential mechanisms of Moslae Herba extract (MHE) on alleviating HUA in mice.

METHODS

The ingredients of MHE were analyzed using UHPLC-QE-MS/MS. The HUA mouse model was established by potassium oxonate (PO) and hypoxanthine (HX) to evaluate the anti-HUA effect of MHE. Molecular docking, in vitro enzyme inhibition assays and microscale thermophoresis (MST) were performed to assess the inhibitory effects of ingredients on xanthine oxidase (XOD). Targets and signaling pathways regulated by MHE were predicted through network pharmacology analysis. Fecal 16S rRNA gene sequencing was used to analyze alterations in gut microbiota.

RESULTS

14 ingredients of MHE were identified using UHPLC-QE-MS/MS. MHE effectively alleviated HUA in mice induced by PO and HX. Mechanistically, MHE dually regulated XOD and ATP-binding cassette subfamily G member 2 (ABCG2) to decrease synthesis and promote intestinal and renal excretion of uric acid. Network pharmacology analysis and protein-level validation indicated that MHE relieved HUA-induced renal inflammation and fibrosis by suppressing the NLRP3 inflammasome and JAK2/STAT3 signaling pathway. 16S rRNA gene sequencing results suggested that MHE might further alleviate HUA and maintain intestinal homeostasis by modulating the gut microbiota.

CONCLUSION

This study is the first to demonstrate that MHE exerts anti-HUA effects through multiple mechanisms, providing novel insights for the phytotherapeutic management of HUA.

摘要

背景

高尿酸血症(HUA)是一种由尿酸代谢紊乱引起的代谢性疾病,在全球范围内普遍存在。石香薷是一种传统草药,以其抗炎、抗氧化和利尿作用而闻名。

目的

本研究旨在探讨石香薷提取物(MHE)对缓解小鼠高尿酸血症的作用及其潜在机制。

方法

采用超高效液相色谱-四极杆飞行时间质谱联用仪(UHPLC-QE-MS/MS)分析MHE的成分。通过氧嗪酸钾(PO)和次黄嘌呤(HX)建立高尿酸血症小鼠模型,以评估MHE的抗高尿酸血症作用。进行分子对接、体外酶抑制试验和微量热泳动(MST),以评估成分对黄嘌呤氧化酶(XOD)的抑制作用。通过网络药理学分析预测MHE调控的靶点和信号通路。采用粪便16S rRNA基因测序分析肠道微生物群的变化。

结果

利用UHPLC-QE-MS/MS鉴定出MHE的14种成分。MHE有效缓解了PO和HX诱导的小鼠高尿酸血症。机制上,MHE双重调节XOD和ATP结合盒转运体G成员2(ABCG2),以减少尿酸合成并促进肠道和肾脏尿酸排泄。网络药理学分析和蛋白质水平验证表明,MHE通过抑制NLRP3炎性小体和JAK2/STAT3信号通路减轻高尿酸血症诱导的肾脏炎症和纤维化。16S rRNA基因测序结果表明,MHE可能通过调节肠道微生物群进一步缓解高尿酸血症并维持肠道稳态。

结论

本研究首次证明MHE通过多种机制发挥抗高尿酸血症作用,为高尿酸血症的植物治疗管理提供了新的见解。

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