Xiaoshuan Tongluo recipe alleviated acute hyperglycemia-enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke rats

Backgrounds: Hemorrhagic transformation (HT) is a complication after stroke and is associated with increased mortality and disability. Hyperglycemia is a risk factor for HT incidence and seriously affects the treatment of stroke. There are no effective drugs to cure HT in the clinic. The Xiaoshuan T...

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Main Authors: Zirong Pan, Nannan Liu, Guodong Ma, Sen Zhang, Chengdi Liu, Ziyuan Zhao, Linglei Kong, Guanhua Du
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Pharmacological Research - Modern Chinese Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S266714252300101X
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author Zirong Pan
Nannan Liu
Guodong Ma
Sen Zhang
Chengdi Liu
Ziyuan Zhao
Linglei Kong
Guanhua Du
author_facet Zirong Pan
Nannan Liu
Guodong Ma
Sen Zhang
Chengdi Liu
Ziyuan Zhao
Linglei Kong
Guanhua Du
author_sort Zirong Pan
collection DOAJ
description Backgrounds: Hemorrhagic transformation (HT) is a complication after stroke and is associated with increased mortality and disability. Hyperglycemia is a risk factor for HT incidence and seriously affects the treatment of stroke. There are no effective drugs to cure HT in the clinic. The Xiaoshuan Tongluo effective component group (XECG) is a Chinese medicine formula reconstituted by active ingredients, which is clinically used for the treatment of stroke. However, the roles of XECG in hyperglycemia-enhanced HT are not clear. This study aims to evaluate the effects of XECG on hyperglycemia-enhanced HT and explore the potential mechanisms. Methods: In this study, a hyperglycemia-induced HT model was used. XECG (100, 200, 400 mg·kg−1) was orally administered for 5 days before the operation, and the incidence of HT was evaluated. Microglia polarization and related signaling pathways were measured to clarify the mechanisms of XECG on hyperglycemia-induced HT. Results: Our results revealed that pretreatment with XECG alleviated neurological deficits and BBB disruption and improved the incidence and severity of HT enhanced by hyperglycemia. Further studies confirmed that XECG regulated microglial polarization by inhibiting the M1 phenotype and promoting the M2 phenotype and inhibited the activation of the HMGB1-RAGE-NF-κB signaling pathway. Conclusions: These results suggested that pretreatment with XECG alleviated hyperglycemia-enhanced HT. XECG may be a potential drug for the treatment of HT.
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spelling doaj.art-49ef4b2153d94519a05065b1891ed6ec2023-12-17T06:42:55ZengElsevierPharmacological Research - Modern Chinese Medicine2667-14252023-12-019100315Xiaoshuan Tongluo recipe alleviated acute hyperglycemia-enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke ratsZirong Pan0Nannan Liu1Guodong Ma2Sen Zhang3Chengdi Liu4Ziyuan Zhao5Linglei Kong6Guanhua Du7Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, PR ChinaBeijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, PR ChinaBeijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, PR ChinaBeijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, PR ChinaBeijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, PR China; Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, PR ChinaBeijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, PR ChinaBeijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, PR China; Corresponding authors.Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1 Xiannongtan Street, Xicheng District, Beijing 100050, PR China; Corresponding authors.Backgrounds: Hemorrhagic transformation (HT) is a complication after stroke and is associated with increased mortality and disability. Hyperglycemia is a risk factor for HT incidence and seriously affects the treatment of stroke. There are no effective drugs to cure HT in the clinic. The Xiaoshuan Tongluo effective component group (XECG) is a Chinese medicine formula reconstituted by active ingredients, which is clinically used for the treatment of stroke. However, the roles of XECG in hyperglycemia-enhanced HT are not clear. This study aims to evaluate the effects of XECG on hyperglycemia-enhanced HT and explore the potential mechanisms. Methods: In this study, a hyperglycemia-induced HT model was used. XECG (100, 200, 400 mg·kg−1) was orally administered for 5 days before the operation, and the incidence of HT was evaluated. Microglia polarization and related signaling pathways were measured to clarify the mechanisms of XECG on hyperglycemia-induced HT. Results: Our results revealed that pretreatment with XECG alleviated neurological deficits and BBB disruption and improved the incidence and severity of HT enhanced by hyperglycemia. Further studies confirmed that XECG regulated microglial polarization by inhibiting the M1 phenotype and promoting the M2 phenotype and inhibited the activation of the HMGB1-RAGE-NF-κB signaling pathway. Conclusions: These results suggested that pretreatment with XECG alleviated hyperglycemia-enhanced HT. XECG may be a potential drug for the treatment of HT.http://www.sciencedirect.com/science/article/pii/S266714252300101XXiaoshuan Tongluo recipeStrokeHyperglycemiaHemorrhagic transformationBlood-brain barrierMicroglia polarization
spellingShingle Zirong Pan
Nannan Liu
Guodong Ma
Sen Zhang
Chengdi Liu
Ziyuan Zhao
Linglei Kong
Guanhua Du
Xiaoshuan Tongluo recipe alleviated acute hyperglycemia-enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke rats
Pharmacological Research - Modern Chinese Medicine
Xiaoshuan Tongluo recipe
Stroke
Hyperglycemia
Hemorrhagic transformation
Blood-brain barrier
Microglia polarization
title Xiaoshuan Tongluo recipe alleviated acute hyperglycemia-enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke rats
title_full Xiaoshuan Tongluo recipe alleviated acute hyperglycemia-enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke rats
title_fullStr Xiaoshuan Tongluo recipe alleviated acute hyperglycemia-enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke rats
title_full_unstemmed Xiaoshuan Tongluo recipe alleviated acute hyperglycemia-enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke rats
title_short Xiaoshuan Tongluo recipe alleviated acute hyperglycemia-enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke rats
title_sort xiaoshuan tongluo recipe alleviated acute hyperglycemia enhanced hemorrhagic transformation by regulating microglia polarization in thromboembolic stroke rats
topic Xiaoshuan Tongluo recipe
Stroke
Hyperglycemia
Hemorrhagic transformation
Blood-brain barrier
Microglia polarization
url http://www.sciencedirect.com/science/article/pii/S266714252300101X
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