Potential mechanisms of baicalin-geniposide combination against cerebral ischemia: An integrated study of network pharmacology and experimental validation

Jing Ji; Tian Xu; Zijin Sun; Haojia Zhang; Qi Shao; Chongyang Ma; Hanrui Zhang; Fafeng Cheng; Xueqian Wang; Qingguo Wang

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Potential mechanisms of baicalin-geniposide combination against cerebral ischemia: An integrated study of network pharmacology and experimental validation

Author: Jing Ji ¹ ; Tian Xu ² ; Zijin Sun ¹ ; Haojia Zhang ¹ ; Qi Shao ¹ ; Chongyang Ma ³ ; Hanrui Zhang ⁴ ; Fafeng Cheng ¹ ; Xueqian Wang ¹ ; Qingguo Wang ¹
Author Information

1. School of Traditional Chinese Medicine, Beijing University of Chinese Medicine,Beijing,China,102488
2. Peking Union Medical College, Chinese Academy of Medical Sciences,Beijing,China,100730
3. School of Traditional Chinese Medicine, Capital Medical University,Beijing,China,100069
4. Department of Medicine, Columbia University,NY,New York,USA,10032
Publication Type:Journal Article
Keywords: Cerebral ischemia; Baicalin; Geniposide; Drug combination; Network pharmacology
From: Journal of Traditional Chinese Medical Sciences 2025;2025(4):531-541
CountryChina
Language:English
Abstract: ObjectiveTo explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.MethodWe used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin (55 mg/kg), geniposide (5 mg/kg), or their 11:1 combination. Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining, Evans blue assay, enzyme-linked immunosorbent assay, and Western blot.ResultsThe results revealed that the nuclear factor-kappa B (NF-κB) signaling pathway is inhibited in combination treatment of cerebral ischemia. Ten targets were identified as key nodes in the protein–protein interaction network: interleukin 6 (IL-6), interleukin-1β, interleukin 18, C–C motif ligand 2, C–C motif ligand 4, interleukin 10, interferon-γ-inducible protein 10, C–C motif ligand 3, tumor necrosis factor-α (TNF-α), interleukin-1α. The baicalin-geniposide combination significantly reduced infarct volume, improved neurological deficits, and alleviated brain edema/blood–brain barrier leakage compared with monotherapy. Additionally, it significantly inhibited toll-like receptor 4 (TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-α and IL-6 levels.ConclusionThe baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.