The Traditional Chinese Medicine Compound, GRS, Alleviates Blood–Brain Barrier Dysfunction

• Main Authors: Zhang Y, Hu Y, Li M, Wang J, Guo G, Li F, Yu B, Kou J
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-02-01
• Series: Drug Design, Development and Therapy
• Subjects: grs; ischemic stroke; blood-brain barrier; endothelial; tight junctions; rock/cofilin
• Online Access: https://www.dovepress.com/the-traditional-chinese-medicine-compound-grs-alleviates-blood-brain-b-peer-reviewed-article-DDDT

Yuanyuan Zhang, Yang Hu, Min Li, Jieman Wang, Gengshuo Guo, Fang Li, Boyang Yu, Junping Kou Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of ChinaCorrespondence: Boyang Yu; Junping KouJiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, People’s Republic of ChinaTel [phone]Fax [phone]Email [e-mail]; [e-mail]: Traditional Chinese medicine (TCM) provides unique advantages for treatment of ischemic stroke, an aging-related vascular disease. Shengmai powder (GRS) is composed of three active components, specifically, ginsenoside Rb1, ruscogenin and schisandrin A, at a ratio of 6:0.75:6. The main objective of this study was to evaluate the effects of GRS on blood–brain barrier (BBB) dysfunction under conditions of middle cerebral artery occlusion/reperfusion (MCAO/R).Methods: C57BL/6J mice subjected to MCAO/R were used as a model to assess the protective effects of varying doses of GRS (6.4, 12.8, and 19.2 mg/kg) on BBB dysfunction.Results: GRS reduced cerebral infarct volume and degree of brain tissue damage, improved behavioral scores, decreased water content and BBB permeability, and restored cerebral blood flow. Moreover, GRS promoted expression of zona occludens-1 (ZO-1) and claudin-5 while inhibiting matrix metalloproteinase 2/9 (MMP-2/9) expression and myosin light chain (MLC) phosphorylation. In vitro, GRS (1, 10, and 100 ng/mL) enhanced the viability of bEnd.3 cells subjected to oxygen glucose deprivation/reoxygenation (OGD/R) and decreased sodium fluorescein permeability.Conclusion: Consistent with in vivo findings, ZO-1 and claudin-5 were significantly upregulated by GRS in bEnd.3 cells under OGD/R and MMP-2/9 levels and MLC phosphorylation reduced through the Rho-associated coil-forming protein kinase (ROCK)/cofilin signaling pathway. Based on the collective findings, we propose that the TCM compound, GRS, plays a protective role against I/R-induced BBB dysfunction.Keywords: GRS, ischemic stroke, blood–brain barrier, endothelial, tight junctions, ROCK/cofilin