School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai.
Neuroreport. 2024 Nov 6;35(16):1041-1051. doi: 10.1097/WNR.0000000000002099. Epub 2024 Sep 19.
Even though considerable progress has been made to reduce insult, ischemic stroke is still a significant cause of mortality and morbidity in the world, and new therapeutic strategies are urgently needed. In the present study, the magnesium salt of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1) combination as a multicomponent strategy against stroke was evaluated. The synergistic effect of Sa1B and Rg1 was evaluated by Bliss independence analysis on the middle cerebral artery occlusion model. The infarct volume, neuroethology, cerebral structure, and neurocyte number were evaluated by 3,5-triphenyltetrazolium chloride staining, Longa score, Garcia score, hematoxylin-eosin staining, and Nissl staining, respectively. Metabolomics was used to search for potential biomarkers and explore the mechanism of Sa1B/Rg1. First, the superior effects of SalB/Rg1 than SalB or Rg1 at the same dose were evaluated. Compared with SalB ( P < 0.001) or Rg1 ( P < 0.01), SalB/Rg1 significantly decreased infarct volume through 3,5-triphenyltetrazolium chloride staining and protected the structural integrity of cortex and striatum. The superior effect of SalB/Rg1 on neurological behavior was also detected compared with SalB or Rg1 significantly. Accompanying behavioral improvement, a considerable increase of SalB/Rg1 on neurons detected by Nissl staining was found on the cortex compared with SalB ( P < 0.05) or Rg1 ( P < 0.01). Second, the synergistic effect between SalB and Rg1 was strictly verified by Bliss independence analysis ( P < 0.01) based on infarct volume. Finally, alleviation of cerebral metabolic disorders may be the possible mechanism of SalB/Rg1. Our study provided a multicomponent strategy against ischemic stroke, with not only dose reduction but also improved efficacy relative to single agents.
尽管在减轻损伤方面已经取得了相当大的进展，但缺血性中风仍然是世界上导致死亡率和发病率的一个重要原因，因此急需新的治疗策略。在本研究中，评估了丹酚酸 B 镁盐（SalB）和人参皂苷 Rg1（Rg1）联合作为一种针对中风的多成分策略。通过对大脑中动脉闭塞模型的 Bliss 独立性分析来评估 Sa1B 和 Rg1 的协同作用。通过 3,5-三苯基氯化四氮唑染色评估梗死体积、神经行为学、脑结构和神经细胞数量，通过 Longa 评分、Garcia 评分、苏木精-伊红染色和尼氏染色评估。代谢组学用于寻找潜在的生物标志物并探索 Sa1B/Rg1 的作用机制。首先，评估了 SalB/Rg1 与相同剂量的 SalB 或 Rg1 相比的优越效果。与 SalB（P ＜0.001）或 Rg1（P ＜0.01）相比，SalB/Rg1 通过 3,5-三苯基氯化四氮唑染色显著降低梗死体积，保护皮质和纹状体的结构完整性。SalB/Rg1 在神经行为方面的优越效果也明显优于 SalB 或 Rg1。伴随行为改善，与 SalB（P ＜0.05）或 Rg1（P ＜0.01）相比，在皮质中发现 SalB/Rg1 对神经元的增加更为明显。其次，基于梗死体积，通过 Bliss 独立性分析严格验证了 Sa1B 和 Rg1 之间的协同作用（P ＜0.01）。最后，减轻脑代谢紊乱可能是 Sa1B/Rg1 的可能作用机制。我们的研究提供了一种针对缺血性中风的多成分策略，与单一药物相比，不仅剂量减少，而且疗效提高。
