Regulation of Histidine Metabolism by Mediates the Pathogenesis and Treatment of Ischemic Stroke

Overview

Journal Acta Pharm Sin B

Publisher Elsevier

Specialty Pharmacology

Date 2025 Mar 5

PMID 40041923

Authors

Kangrui Hu

Zhihao Zhou

Haofeng Li

Jijun Xiao

Yun Shen

Ke Ding

Tingting Zhang

Guangji Wang

Haiping Hao

Yan Liang

Affiliations

Soon will be listed here.

Abstract

Increasing evidence has underscored the significance of post-stroke alterations along gut-brain axis, while its role in pathogenesis and treatment of ischemic stroke (IS) remains largely unexplored. This study aimed to elucidate the therapeutic effects and action targets of (PNS) on IS and explore a novel pathogenesis and treatment strategy of IS profiling the microbial community and metabolic characteristics along gut-brain axis. Our findings revealed for the first time that the therapeutic effect of PNS on IS was microbiota-dependent. Ischemia/reperfusion (I/R) modeling significantly down-regulated in rats, and PNS markedly recovered , particularly (). Metabolomics showed a significant reduction in serum histidine (HIS) in clinical obsolete IS patients and rehabilitation period I/R rats. Meanwhile, the colonization in I/R rats exhibited significant neuroprotective activity and greatly increased HIS in serum, gut microbiota, and brain. Moreover, exogenous HIS demonstrated indirect neuroprotective effects through metabolizing to histamine. Notably, vagus nerve severance in I/R rats was performed to investigate HIS's neuroprotective mechanism. The results innovatively revealed that PNS could promote HIS synthesis in gut by enhancing proportion, thereby increasing intracerebral HIS through peripheral pathway. Consequently, our data provided novel insights into HIS metabolism mediated by in the pathogenesis and treatment of IS.

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