Effect and mechanism of Buyang Huanwu Decoction in improving neurological function in ischemic stroke rats based on IRE1α/ASK1/JNK pathway.
10.19540/j.cnki.cjcmm.20250416.501
- Author:
Xin-Rong ZHANG
1
;
Tian-Lang WANG
1
;
Jia-Hao ZHANG
1
;
Lu JIN
1
;
Jian-Bo WANG
2
;
Ya-Nan XUE
3
;
Yi QU
2
Author Information
1. Liaoning University of Traditional Chinese Medicine Shenyang 110847, China.
2. Liaoning University of Traditional Chinese Medicine Shenyang 110847, China Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera-State Theory and Applications,Liaoning University of Traditional Chinese Medicine Shenyang 110847, China National and Local Joint Engineering Laboratory for Integrated Chinese and Western Medicine Prevention and Treatment Technology on Cardio-Brain Diseases, Liaoning University of Traditional Chinese Medicine Shenyang 110847, China.
3. Liaoning University of Traditional Chinese Medicine Shenyang 110847, China Key Laboratory of Ministry of Education for Traditional Chinese Medicine Viscera-State Theory and Applications,Liaoning University of Traditional Chinese Medicine Shenyang 110847, China Acupuncture and Moxibustion and Massage College, Liaoning University of Traditional Chinese Medicine Shenyang 110847, China.
- Publication Type:Journal Article
- Keywords:
Buyang Huanwu Decoction;
IRE1α/ASK1/JNK pathway;
cerebral ischemia/reperfusion injury;
endoplasmic reticulum stress
- MeSH:
Animals;
Male;
Rats, Sprague-Dawley;
Protein Serine-Threonine Kinases/genetics*;
Drugs, Chinese Herbal/administration & dosage*;
Rats;
MAP Kinase Kinase Kinase 5/genetics*;
Ischemic Stroke/physiopathology*;
Humans;
MAP Kinase Signaling System/drug effects*;
Apoptosis/drug effects*;
Endoribonucleases/genetics*;
JNK Mitogen-Activated Protein Kinases/genetics*;
Endoplasmic Reticulum Stress/drug effects*;
Multienzyme Complexes
- From:
China Journal of Chinese Materia Medica
2025;50(14):3857-3867
- CountryChina
- Language:Chinese
-
Abstract:
This study aimed to investigate the effect and mechanism of Buyang Huanwu Decoction in regulating endoplasmic reticulum stress via the inositol-requiring enzyme 1α(IRE1α)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway to improve neurological function in rats with cerebral ischemia/reperfusion injury(CIRI). SPF-grade male sprague-dawley(SD) rats were randomly divided into Sham group, model group, Buyang Huanwu Decoction group, and edaravone group. Except for the Sham group, the other groups were subjected to the modified suture method to establish a middle cerebral artery occlusion/reperfusion(MCAO/R) model. After treatment, neurological function was assessed using the Zea Longa scoring system. Gait analysis was used to detect the motor function. Detection of relative infarct area in brain tissue using 2,3,5-triphenyltetrazolium chloride(TTC) staining. Nissl staining was used to observe the structure of neuronal cells. Western blot and real-time fluorescence quantitative PCR(RT-qPCR) were used to detect IRE1α, ASK1, JNK, B cell lymphoma-2(Bcl-2), Bcl-2 related X protein(Bax), and Caspase-3 in the brain tissue. Immunohistochemistry was used to detect the positive expression of IRE1α, ASK1, and JNK. Immunofluorescence was used to detect the fluorescence expression levels of Bax, Bcl-2, and Caspase-3. The results showed that compared with the Sham group, the model group exhibited increased neurological scores(P<0.01), increased ratio of ground contact area and strength in both forelimbs(P<0.01), enlarged relative infarct area of brain tissue(P<0.05), and a reduced number of Nissl staining-positive cells(P<0.01). The protein and mRNA expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 in brain tissue were significantly elevated, while those of Bcl-2 were decreased(P<0.05). Compared with the model group, both the Buyang Huanwu Decoction group and edaravone group showed reduced neurological scores(P<0.05), decreased ratio of ground contact area and strength in both forelimbs(P<0.05), smaller relative infarct area(P<0.05), alleviated neuronal damage, and increased number of Nissl staining-positive cells(P<0.05). The expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 protein and mRNA in brain tissue were significantly reduced, while those of Bcl-2 were significantly increased(P<0.05). The results indicated that Buyang Huanwu Decoction can effectively improve brain injury in CIRI rats, and its mechanism of action may be related to regulating the endoplasmic reticulum stress IRE1α/ASK1/JNK signaling pathway.
