The Effects of Baicalin and Geniposide in Combination on Microglial Activation and 5-Lipoxygenase Expression in Rats during Recovery from Cerebral Ischemia

Abstract

Background and objectives This study aimed to analyze the effects of baicalin (BC) and geniposide (GP) in combination (7:3) on the activation of microglia (MG) and 5-lipoxygenase (5-LOX) expression in rats during the recovery period after cerebral ischemia and to determine whether inhibition of the 5-LOX pathway is beneficial for M1-to-M2 polarization of MG.

Methods Sprague Dawley rats were divided into five groups: control, model, and BC/GP (7:3) at 30, 45, and 60 mg/kg. A permanent middle artery occlusion model was established using the thread embolism method, and recovery after cerebral ischemia was monitored for 5 weeks. The effects on microglial activation and 5-LOX expression were evaluated by the neurofunctional score and immunofluorescence double labeling. The gene expression of 5-LOX in MG was determined by quantitative polymerase chain reaction before and after drug administration. The gene expression of tumor necrosis factor alpha, inducible nitric oxide synthase, interleukin 10, and cluster of differentiation 206 in MG was determined after the administration of zileuton (depressor). Western blotting was performed to determine the protein expression of 5-LOX, cysteinyl leukotriene receptor 1, cysteinyl leukotriene receptor 2, leukotriene B4 receptor 1, and leukotriene B4 receptor 2 before and after the administration of zileuton.

Results The activation of MG and the expression of 5-LOX were both increased after cerebral ischemia. BC/GP in combination inhibited the activation of microglia-reduced expression of 5-LOX and induced M2 polarization of MG.

Conclusion The combination of BC and GP downregulates the 5-LOX inflammatory pathway by inhibiting activation of MG and promotes M1-to-M2 polarization of MG. Neurons are protected by the M2-type polarization, resulting in alleviation of cerebral ischemia.

Keywords

Recovery from cerebral ischemic injury / Baicalin / Gardenia / Microglia / Microglial cell polarization / 5-LOX

Acknowledgments

We would like to thank International Science Editing for the lan-guage polishing of the manuscript.

Funding

This research was supported by grants from the National Natural Science Foundation of China (Grant no. 81473385), the Shaanxi Traditional Chinese Medicine Scientific Research Project (Grant no. 2021-ZZ-JC023), and the Subject Innovation Team of Shaanxi University of Chinese Medicine (Grant no. 2019-YL13). Chinese medicine “double-chain fusion” young and middle-aged scientific research and innovation team, project number 2022-SLRH-YQ-006.

Conflict of interest

Bin Wang has been an editorial board member of Future Integra-tive Medicine since June 2023. The authors have no other conflict of interests to report.

Author contributions

YW: conceptualization, supervision, data curation, writing of the original draft, writing of the review, and critical revision of the manuscript. HL: acquisition and analysis of data. JW: acquisi-tion and analysis of data. LZ: investigation and acquisition of the data. HHZ: investigation and acquisition of the data. QQS: assay performance and data analysis. ADZ: assay performance and data analysis. HFZ: conceptualization, supervision, validation, writing of the review, and editing. BW: conceptualization, supervision, validation, writing of the review, and editing. All authors read and approved the final manuscript.

Data sharing statement

The data used to support the findings of the study are included in the article.

Ethical statement

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