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Journal of Traditional Chinese Medicine >

2024 , Vol. 44 >Issue 4: 794 - 803

DOI: https://doi.org/10.19852/j.cnki.jtcm.20240515.001

Original articles

Sanhua Tang (三化汤) protects against ischemic stroke by preventing blood-brain barrier injury: a network pharmacology and in vivo experiments

  • Shan LUO ,
  • Fan YANG ,
  • Yuanchun CHEN ,
  • Ruoxi ZHAO ,
  • Haiye LIU ,
  • Fei GAO ,
  • Wencan MA ,
  • Weijuan GAO ,
  • Wentao YU
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  • 1 College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China
    2 Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050091, China
    3 College of Acupuncture and Massage, Hebei University of Chinese Medicine, Shijiazhuang 050200, China
    4 Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Diseases, Shijiazhuang 050091, China
    5 Hebei International Joint Research Centre for Acupuncture and Moxibustion of Traditional Chinese Medicine, Shijiazhuang 050091, China

Received date: 2023-01-11

  Accepted date: 2023-07-16

  Online published: 2024-05-15

Supported by

Hebei Province Natural Science Foundation Project: Based on The Xuan Fu Theory to Explore Sanhua Tang on Ischemic Stroke Blood-brain Barrier Protection Mechanism Research(H2022423327);Science and Technology Program of Hebei Provincial Administration of Traditional Chinese Medicine: based on The Changes in Gut Microbiota, Explore Sanhua Tang From The Perspective of "Opening the Xuan Fu" Protective Phlegm Heat Relieving Excess Syndrome of Ischemic Stroke Mechanism of Action of the Blood-brain Barrier(2022090);Hebei Key Laboratory of Chinese Medicine Research on Cardio- cerebrovascular Disease in 2021 Project:Based on the Gut-brain Axis, Explore Sanhua Tang's Treatment of Ischemic Stroke Syndrome (Phlegm Heat Relieving Empirical Model)(2021201);Innovation Funding Program for Doctoral Students in Hebei Province: the Mechanism Research of Sanhua Tang Regulating Gut Microbiota, Improving the Blood-brain Barrier Damage of Ischemic Stroke(CXZZBS2022095);National College Students' Innovation and Entrepreneurship Training Program: Based on the Xuan Fu Theory to Explore Sanhua Tang on Ischemic stroke Blood-brain Barrier Protection Mechanism Research(202114432005);Special Project on the Cultivation of Scientific and Technological Innovation Ability of College and Middle School Students in Hebei Province: Mechanism Research of Bushen Huoxue Fang on Synaptic Plasticity in the Hippocampal Nerve After Vascular Dementia through Phosphatidylinositide 3-Kinase/Protein Kinase b/Mammalian Target of Rapamycin Signaling Pathways(22E50142D)

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Abstract

OBJECTIVE: To assess the effect and mechanism of Sanhua Tang (三化汤, SHT) in treating ischemic stroke (IS) through the "Kaitong Xuanfu" theory by using network pharmacology and animal experiments.

METHODS: The active ingredients and targets of SHT and IS were screened by public databases such as Traditional Chinese Medicine systems pharmacology, GeneCards, and online mendelian inheritance in man. Visual network topographies were constructed using R, Cytoscape 3.6.0, AutoDockTools, a user-sponsored molecular visualization system on an open-source foundation, and other software to analyze the correlation between targets and active ingredients. The middle cerebral artery occlusion (MCAO) model was established by operation. Animals were divided into the Sham group, MCAO group (M group), aloe-emodin (AE) group (MCAO rats treated with aloe-emodin), SHT at low dosage (SL group) (MCAO rats treated with SL), SHT at medium dosage (SM group), and SHT at high dosage (SH group). 2,3,5-triphenyl tetrazolium chloride staining was used to detect the volume of cerebral infarction; Nissl staining was used to observe the morphology of neuronal cells; transmission electron microscopy was used to observe the integrity of the blood-brain barrier (BBB); enzyme-linked immunosorbent assay was used to detect the content of interleukin-6 (IL-6), IL-10, tumor necrosis factor α (TNF-α) in serum. Western blot was used to detect the expression of vascular endothelial growth factor A (VEGFA) protein in the cerebral ischemic penumbra.

RESULTS: Using network pharmacology and molecular docking validation, four active ingredients (lignan, naringenin, aloe-rhodopsin, and β-sitosterol), seven target proteins (protein kinase b 1, IL-6, TNF, VEGFA, TP53, jun proto-oncogene, and cysteinyl aspartate specific proteinase 3), and inflammatory signaling pathways were identified. Animal experiments showed that the SH and AE groups had fewer neurological deficits, reduced brain infarct volumes, decreased serum inflammatory factor levels, increased expression of VEGFA protein, and less structural damage to neurons and BBB.

CONCLUSION: The present study found that the therapeutic mechanism of SHT against IS may be related to the inhibition of BBB inflammatory damage, which is also the mechanism of "Kaitong Xuanfu." The high-dose group of SHT was relatively effective in regulating inflammatory factors, improving BBB permeability, and protecting neuronal cells from damage.

Key words： network pharmacology; ischemic stroke; blood-brain barrier; inflammatory reactions; Sanhua Tang

Cite this article

Shan LUO , Fan YANG , Yuanchun CHEN , Ruoxi ZHAO , Haiye LIU , Fei GAO , Wencan MA , Weijuan GAO , Wentao YU . Sanhua Tang (三化汤) protects against ischemic stroke by preventing blood-brain barrier injury: a network pharmacology and in vivo experiments[J]. Journal of Traditional Chinese Medicine, 2024 , 44(4) : 794 -803 . DOI: 10.19852/j.cnki.jtcm.20240515.001

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