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CC BY 4.0 · Chinese medicine and natural products 2023; 03(02): e81-e89
DOI: 10.1055/s-0043-1770074
Original Article

Inhibition of Salvianolic Acid B and Ginsenoside Rg1 on Hemorrhagic Transformation after Stroke

Rongrong Xing
1   School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, China
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
Yiyu Wang
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
Linlin Wang
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
Haishang Shen
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
Yi Jin
3   Shenzhen Institute for Drug Control, Shenzhen Testing center of medical devices, Shenzhen, China
,
Haoying Yu
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
,
Rongxia Liu
1   School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, China
,
Baohong Jiang
2   Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
› Institutsangaben
Funding This study was supported by the Biological Resources Programme, Chinese Academy of Sciences (KFJ-BRP-008-005); Shanghai Science and Technology Development Foundation (21S21901900); the Lingang Laboratory Grant (LG-QS-202206-01); Ministry of Science and Technology of China (2021YFE0111300); National Natural Science Foundation of China (81973513, 81573646).
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Abstract

Objective Application of recanalization on stroke patients is not only limited with time window, but also accompanied with the risk of hemorrhagic transformation. In present study, the effects of salvianolic acid B and ginsenoside Rg1 combination (SalB/Rg1) on time window and hemorrhagic transformation against ischemic stroke was evaluated on middle cerebral artery occlusion (MCAO) mice.

Methods The protection and time window of SalB/Rg1 were estimated through infarct volume, neurobehavioral deficits, and histomorphological examination. The prohibition of SalB/Rg1 against hemorrhagic transformation was detected on MCAO mice stimulated with dextrose and reperfusion. Hemorrhagic transformation was assessed by the Heidelberg Bleeding Classification. The mechanism of SalB/Rg1 against hemorrhagic transformation was identified by immunofluorescence staining and in situ gelatin zymography.

Results First, SalB/Rg1 significantly reduced infarct volume and improved neurobehavior in a dose-dependent manner. Then, the protective time window up to 9 hours was detected for SalB/Rg1 against stroke. Both the dose-dependent efficiency and longtime protection of SalB/Rg1 were further identified based on cytoarchitecture through histopathological stain. Second, SalB/Rg1 downregulated hemorrhagic score, infarct volume, and abnormal neurobehavior. Finally, the inhibition of SalB/Rg1 against hemorrhagic transformation was found to accompany with its protection on the integrity of neurovascular unit. Around the edge area of infarction, SalB/Rg1 attenuated the astrocyte activation, maintained the abundance of junction protein (claudin-5) between endothelial cells, considerably decreased matrix metallopeptidase 9 activity through in situ gelatin zymography.

Conclusion SalB/Rg1 is a promising strategy for further development against stroke, especially against hemorrhagic transformation.

Keywords

stroke - salvianolic acid B - ginsenoside Rg1 - hemorrhagic transformation - neurovascular unit

Animal Ethics Approval

All animal care and experimental procedures were approved by the Institutional Animal Care and Use Committee at Shanghai Institute of Materia Medica (IACUC No.: 2021-04-GDA-77).


CRediT Authorship Contribution Statement

R.X.: Conceptualization, methodology, data curation, and writing original draft. Y.W.: Conceptualization, methodology, resources, data curation, investigation. L.W.: Conceptualization, methodology. H.S., Y.J. and H.Y.: Resources, data curation, investigation, software. B.J. and R.L.: Funding acquisition, supervision, writing review, and editing.


Supplementary Material



Publikationsverlauf

Eingereicht: 01. Dezember 2022

Angenommen: 22. Januar 2023

Artikel online veröffentlicht:
28. Juni 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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