Neuroprotective and vasoprotective effects of herb pair of Zhiqiao-Danggui in ischemic stroke uncovered by LC-MS/MS-based metabolomics approach

• Published in: Metabolic brain disease 2024-08, Vol.39 (6), p.1131-1148
• Main Authors: Yao, Benxing, Xu, Di, Wang, Qing, Liu, Lin, Hu, Ziyun, Liu, Wenya, Zheng, Qi, Meng, Huihui, Xiao, Ran, Xu, Qian, Hu, Yudie, Wang, Junsong
• Format: Article
• Language: English
• Subjects: Amino acids; Angiogenesis; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Blood circulation; Blood vessels; Cell proliferation; Cell size; Cell survival; Chromatography, Liquid; Damage; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Endothelial cells; Energy metabolism; Herbal medicine; Herbs; Histopathology; Ischemia; Ischemic Stroke - drug therapy; Ischemic Stroke - metabolism; Liquid Chromatography-Mass Spectrometry; Male; Metabolic Diseases; Metabolism; Metabolites; Metabolomics; Mice; Mice, Inbred C57BL; Neurology; Neuroprotection; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Neurosciences; Oncology; Oxidative metabolism; Oxidative stress; Oxidative Stress - drug effects; Stroke; Tandem Mass Spectrometry; Thromboembolism; Thrombosis; Traditional Chinese medicine; Tricarboxylic acid cycle
• ISSN: 1573-7365; 0885-7490; 1573-7365
• DOI: 10.1007/s11011-024-01387-8

Ischemic stroke is the most important cause of disability and death worldwide, but current treatments remain limited. Traditional Chinese medicine (TCM) including the herb pair of Zhiqiao-Danggui (ZD) offers a multifaceted treatment approach through promoting blood circulation, yet its specific anti-ischemic mechanism remains unclear. This study used the photochemically induced thrombosis (PIT) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model to explore the therapeutic effect of ZD on ischemic stroke. Mice were treated with high and low doses of ZD extract or positive control. Behavior was assessed using the grid test. The brain tissue was then subjected to infarct volume assessment, histopathology, oxidative stress marker detection, LC/MS metabolomic analysis and qRT-PCR validation. The therapeutic effect of ZD-medicated serum on OGD/R model was tested on cells. Experimental results show that ZD can improve motor function, reduce infarct size, neuronal damage and apoptosis as well as alleviate oxidative stress in mice. ZD-medicated serum promotes endothelial cell proliferation, improves cell survival against OGD/R-induced injury, reduces oxidative damage and protects mitochondrial function. Metabolomics reveals ZD regulation of metabolites in energy metabolism, amino acid metabolism, TCA cycle, and angiogenesis signaling pathways. qRT-PCR results also showed that ZD could attenuate abnormal conduction of angiogenic signals and enhance vessel stability. This study confirmed the neuroprotective and vasoprotective effects of ZD, highlighted its potential in treating ischemic stroke, and provided a scientific basis for the traditional use of ZD.