Treating ischemic stroke by improving vascular structure and promoting angiogenesis using Taohong Siwu Decoction: An integrative pharmacology strategy

• DOI: 10.1016/j.jep.2024.118372
• Publication Date: 2024-05-20T15:27:15Z
• Authors: Linfeng Tang; Dandan Wang; Hao Chang; Zhuqing Liu; Xueting Zhang; Xuefeng Feng; Lan Han
• Keywords: Male; Rats, Sprague-Dawley; Disease Models, Animal; Neuroprotective Agents; Animals; Neovascularization, Physiologic; Infarction, Middle Cerebral Artery; Angiogenesis Inducing Agents; Angiogenesis; Network Pharmacology; Drugs, Chinese Herbal; Ischemic Stroke; Rats

Neovessels represent a crucial therapeutic target and strategy for repairing ischemic tissue. Taohong Siwu Decoction (THSWD) exhibits potential in promoting angiogenesis to address ischemic stroke (IS). However, its impact on neovessel structure and function, alongside the underlying molecular mechanisms, remains elusive.Our aim is to investigate the protective effects of THSWD on neovessel structure and function, as well as the associated molecular mechanisms, utilizing an integrative pharmacological approach.We initially employed behavioral tests, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Haematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), Laser Doppler flowmetry (LDF), Evans blue staining, and immunofluorescence to evaluate the protective effects of THSWD on neovascular structure and function in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Subsequently, we utilized network pharmacology, metabolomics, and experimental validation to elucidate the underlying molecular mechanisms of THSWD in enhancing neovascular structure and function.In addition to significantly reducing neurological deficits and cerebral infarct volume, THSWD mitigated pathological damage, blood-brain barrier (BBB) leakage, and cerebral blood flow disruption. Moreover, it preserved neovascular structure and stimulated angiogenesis. THSWD demonstrated potential in ameliorating cerebral microvascular metabolic disturbances including lipoic acid metabolism, fructose and mannose metabolism, purine metabolism, and ether lipid metabolism. Consequently, it exhibited multifaceted therapeutic effects, encompassing anti-inflammatory, antioxidant, energy metabolism modulation, and antiplatelet aggregation properties.THSWD exhibited protective effects on cerebral vascular structure and function and facilitated angiogenesis by rectifying cerebral microvascular metabolic disturbances in MCAO/R rats. Furthermore, integrated pharmacology offers a promising approach for studying the intricate traditional Chinese medicine (TCM) system in IS treatment.